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Sample records for albendazole sulfoxide enantiomers

  1. Effect of ruminal microflora on the biotransformation of netobimin, albendazole, albendazole sulfoxide, and albendazole sulfoxide enantiomers in an artificial rumen.

    PubMed

    Capece, B P; Calsamiglia, S; Castells, G; Arboix, M; Cristòfol, C

    2001-05-01

    The effect of ruminal flora on the disposition of benzimidazole anthelmintic drugs was studied in dual-flow continuous-culture fermenters (artificial rumens). Six 1,320-mL artificial rumens were inoculated with ruminal fluid and fermentation conditions were maintained constant at 39 degrees C, pH 6.4, solid dilution rate of 5%/h, and liquid dilution rate of 10%/h to simulate standard ruminal fermentation conditions. The study was repeated in two consecutive periods. Two hours after the inoculation of rumen fluid, the fermenters were fed 30 g of a 60:40 forage:concentrate ration. Within each period two fermenters per treatment were immediately dosed with 104 mg of netobimin, 52 mg of albendazole, or 39 mg of albendazole sulfoxide. Concentrations of netobimin, albendazole, albendazole sulfoxide and its enantiomers, and albendazole sulfone were analyzed by high performance liquid chromatography at 0.25, 0.5, 1, 2, 4, 6, and 8 h after dosage. Reductive metabolism by the ruminal bacteria was observed, favoring the production of albendazole, the most potent anthelmintic molecule. No differences in the production or consumption of albendazole sulfoxide enantiomers were observed, indicating that the ruminal bacteria metabolism was not enantioselective. Because benzimidazole anthelmintic drugs are generally administered orally, the ruminal flora play an important role in the bioavailability of these drugs. In our study, increased concentrations of albendazole in the three treatments, due to reductive ruminal biotransformation, suggests that ruminal biotransformation may improve the efficacy of orally administered netobimin, albendazole, and albendazole sulfoxide.

  2. In Vitro Analysis of Albendazole Sulfoxide Enantiomers Shows that (+)-(R)-Albendazole Sulfoxide Is the Active Enantiomer against Taenia solium

    PubMed Central

    Paredes, Adriana; de Campos Lourenço, Tiago; Marzal, Miguel; Rivera, Andrea; Dorny, Pierre; Mahanty, Siddhartha; Guerra-Giraldez, Cristina; García, Hector H.; Cass, Quezia B.

    2013-01-01

    Albendazole is an anthelmintic drug widely used in the treatment of neurocysticercosis (NCC), an infection of the brain with Taenia solium cysts. However, drug levels of its active metabolite, albendazole sulfoxide (ABZSO), are erratic, likely resulting in decreased efficacy and suboptimal cure rates in NCC. Racemic albendazole sulfoxide is composed of ABZSO (+)-(R)- and (−)-(S) enantiomers that have been shown to differ in pharmacokinetics and activity against other helminths. The antiparasitic activities of racemic ABZSO and its (+)-(R)- and (−)-(S) enantiomers against T. solium cysts were evaluated in vitro. Parasites were collected from naturally infected pigs, cultured, and exposed to the racemic mixture or to each enantiomer (range, 10 to 500 ng/ml) or to praziquantel as a reference drug. The activity of each compound against cysts was assayed by measuring the ability to evaginate and inhibition of alkaline phosphatase (AP) and parasite antigen release. (+)-(R)-ABZSO was significantly more active than (−)-(S)-ABZSO in suppressing the release of AP and antigen into the supernatant in a dose- and time-dependent manner, indicating that most of the activity of ABZSO resides in the (+)-(R) enantiomer. Use of this enantiomer alone may lead to increased efficacy and/or less toxicity compared to albendazole. PMID:23229490

  3. In vitro analysis of albendazole sulfoxide enantiomers shows that (+)-(R)-albendazole sulfoxide is the active enantiomer against Taenia solium.

    PubMed

    Paredes, Adriana; de Campos Lourenço, Tiago; Marzal, Miguel; Rivera, Andrea; Dorny, Pierre; Mahanty, Siddhartha; Guerra-Giraldez, Cristina; García, Hector H; Nash, Theodore E; Cass, Quezia B

    2013-02-01

    Albendazole is an anthelmintic drug widely used in the treatment of neurocysticercosis (NCC), an infection of the brain with Taenia solium cysts. However, drug levels of its active metabolite, albendazole sulfoxide (ABZSO), are erratic, likely resulting in decreased efficacy and suboptimal cure rates in NCC. Racemic albendazole sulfoxide is composed of ABZSO (+)-(R)- and (-)-(S) enantiomers that have been shown to differ in pharmacokinetics and activity against other helminths. The antiparasitic activities of racemic ABZSO and its (+)-(R)- and (-)-(S) enantiomers against T. solium cysts were evaluated in vitro. Parasites were collected from naturally infected pigs, cultured, and exposed to the racemic mixture or to each enantiomer (range, 10 to 500 ng/ml) or to praziquantel as a reference drug. The activity of each compound against cysts was assayed by measuring the ability to evaginate and inhibition of alkaline phosphatase (AP) and parasite antigen release. (+)-(R)-ABZSO was significantly more active than (-)-(S)-ABZSO in suppressing the release of AP and antigen into the supernatant in a dose- and time-dependent manner, indicating that most of the activity of ABZSO resides in the (+)-(R) enantiomer. Use of this enantiomer alone may lead to increased efficacy and/or less toxicity compared to albendazole.

  4. A simple LC-MS/MS method to determine plasma and cerebrospinal fluid levels of albendazole metabolites (albendazole sulfoxide and albendazole sulfone) in patients with neurocysticercosis.

    PubMed

    González-Hernández, Iliana; Ruiz-Olmedo, María Isabel; Cárdenas, Graciela; Jung-Cook, Helgi

    2012-02-01

    The development and validation of an LC-MS/MS method for the simultaneous determination of albendazole metabolites (albendazole sulfoxide and albendazole sulfone) in human plasma are described. Samples of 200 μL were extracted with ether-dichloromethane-chloroform (60:30:10, v/v/v). The chromatographic separation was performed using a C(18) column with methanol-formic acid 20 mmol/L (70:30) as the mobile phase. The method was linear in a range of 20-5000 ng/mL for albendazole sulfoxide and 10-1500 ng/mL for albendazole sulfone. For both analytes the method was precise (RSD < 12%) and accurate (RE <7%) with high recovery (>90%). The method was successfully applied to determine the plasma and cerebrospinal fluid levels of albendazole sulfoxide and albendazole sulfone in patients with subarachnoidal neurocysticercosis who received albendazole at 30 mg/kg per day for 7 days. This LC-MS/MS method yielded a quick, simple and reliable protocol for determining albendazole sulfoxide and albendazole sulfone concentrations in plasma and cerebrospinal fluid samples and is applicable to therapeutic monitoring.

  5. Effect of the water content on the retention and enantioselectivity of albendazole and fenbendazole sulfoxides using amylose-based chiral stationary phases in organic-aqueous conditions.

    PubMed

    Materazzo, Sabrina; Carradori, Simone; Ferretti, Rosella; Gallinella, Bruno; Secci, Daniela; Cirilli, Roberto

    2014-01-31

    Four commercially available immobilized amylose-derived CSPs (Chiralpak IA-3, Chiralpak ID-3, Chiralpak IE-3 and Chiralpak IF-3) were used in the HPLC analysis of the chiral sulfoxides albendazole (ABZ-SO) and fenbendazole (FBZ-SO) and their in vivo sulfide precursor (ABZ and FBZ) and sulfone metabolite (ABZ-SO2 and FBZ-SO2) under organic-aqueous mode. U-shape retention maps, established by varying the water content in the acetonitrile- and ethanol-water mobile phases, were indicative of two retention mechanisms operating on the same CSP. The dual retention behavior of polysaccharide-based CSPs was exploited to design greener enantioselective and chemoselective separations in a short time frame. The enantiomers of ABZ-SO and FBZ-SO were baseline resolved with water-rich mobile phases (with the main component usually being 50-65% water in acetonitrile) on the IF-3 CSP and ethanol-water 100:5 mixture on the IA-3 and IE-3 CSPs. A simultaneous separation of ABZ (or FBZ), enantiomers of the corresponding sulfoxide and sulfone was achieved on the IA-3 using ethanol-water 100:60 (acetonitrile-water 100:100 for FBZ) as a mobile phase.

  6. The self-disproportionation of the enantiomers (SDE) of methyl n-pentyl sulfoxide via achiral, gravity-driven column chromatography: a case study.

    PubMed

    Wzorek, Alicja; Klika, Karel D; Drabowicz, Józef; Sato, Azusa; Aceña, José Luis; Soloshonok, Vadim A

    2014-07-14

    This work explores the self-disproportionation of enantiomers (SDE) of chiral sulfoxides via achiral, gravity-driven column chromatography using methyl n-pentyl sulfoxide as a case study. A major finding of this work is the remarkable persistence and high magnitude of the SDE for the analyte. Thus, it is the first case where SDE is observed even in the presence of MeOH in the mobile phase. The study demonstrated the practical preparation, in line with theory, of enantiomerically pure (>99.9% ee) samples of methyl n-pentyl sulfoxide starting from a sample of only modest ee (<35%). Remarkably, it was found that the order of elution was inverted, i.e. enantiomerically depleted fractions preceded later eluting enantiomerically enriched ones, when the stationary phase was changed from silica gel to aluminum oxide. To the best of our knowledge, this is the first occurrence of inverted SDE behavior due solely to a change in the stationary phase. Aberrant SDE behavior was observed in that the ee did not always fall continuously during the progression of the chromatography, and this was attributed to the complexity of the system at hand which cannot be described in simple terms such as the formation only of homo- and heterochiral dimers based on a single interaction. The results nevertheless suggest that all compounds with a chiral sulfoxide moiety in their structure are likely to exhibit the SDE phenomenon and thus this work constitutes the first example of SDE predictability. Moreover, it could well be that optical purification based on the SDE phenomenon is a simple, convenient, and inexpensive method for the optical purification of this class of compounds with a high degree of proficiency.

  7. Synthesis of an Albendazole Metabolite: Characterization and HPLC Determination

    ERIC Educational Resources Information Center

    Mahler, Graciela; Davyt, Danilo; Gordon, Sandra; Incerti, Marcelo; Nunez, Ivana; Pezaroglo, Horacio; Scarone, Laura; Serra, Gloria; Silvera, Mauricio; Manta, Eduardo

    2008-01-01

    In this laboratory activity, students are introduced to the synthesis of an albendazole metabolite obtained by a sulfide oxidation reaction. Albendazole as well as its metabolite, albendazole sulfoxide, are used as anthelmintic drugs. The oxidation reagent is H[subscript 2]O[subscript 2] in acetic acid. The reaction is environmental friendly,…

  8. Enantioselective renal excretion of albendazole metabolites in patients with neurocysticercosis.

    PubMed

    Lanchote, V L; Takayanagui, O M; Mateus, F H

    2004-10-01

    The present study investigates the urinary excretion of the enantiomers of (+)- and (-)-albendazole sulfoxide (ASOX) and albendazole sulfone (ASON) in 12 patients with neurocysticercosis treated with albendazole for 8 days (7.5 mg/kg/12 h). Serial blood samples (0-12 h) and urine (three periods of 8 h) were collected after administration of the last dose of albendazole. Plasma and urine (+)-ASOX, (-)-ASOX, and ASON metabolites were determined by HPLC using a chiral phase column (Chiralpak AD) with fluorescence detection. The pharmacokinetic parameters (P < 0.05) for (+)-ASOX, (-)-ASOX, and ASON metabolites are reported as means (95% CI); amount excreted (Ae) = 3.19 (1.53-4.85) vs. 0.72 (0.41-1.04) vs. 0.08 (0.03-0.13) mg; plasma concentration-time area under the curve, AUC(0-24) = 3.56 (0.93-6.18) vs. 0.60 (0.12-1.08) vs. 0.38 (0.20-0.55) microg x h/ml, and renal clearance Cl(R) = 1.20 (0.66-1.73) vs. 2.72 (0.39-5.05) vs. 0.25 (0.13-0.37) l/h. Sulfone formation capacity, expressed as the Ae ratio ASON/ASOX + ASON, was 2.21 (1.43-2.99). These data point to enantioselectivity in the renal excretion of ASOX as a complementary mechanism to the metabolism responsible for the plasma accumulation of (+)-ASOX. The results also suggest that the metabolite ASON is partially eliminated as a reaction product of the subsequent metabolism.

  9. In Vitro and In Vivo Drug Interaction Study of Two Lead Combinations, Oxantel Pamoate plus Albendazole and Albendazole plus Mebendazole, for the Treatment of Soil-Transmitted Helminthiasis.

    PubMed

    Cowan, Noemi; Vargas, Mireille; Keiser, Jennifer

    2016-10-01

    The current treatments against Trichuris trichiura, albendazole and mebendazole, are only poorly efficacious. Therefore, combination chemotherapy was recommended for treating soil-transmitted helminthiasis. Albendazole-mebendazole and albendazole-oxantel pamoate have shown promising results in clinical trials. However, in vitro and in vivo drug interaction studies should be performed before their simultaneous treatment can be recommended. Inhibition of human recombinant cytochromes P450 (CYPs) CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 was tested by exposure to albendazole, albendazole sulfoxide, mebendazole, and oxantel pamoate, as well as albendazole-mebendazole, albendazole sulfoxide-mebendazole, albendazole-oxantel pamoate, and albendazole sulfoxide-oxantel pamoate. A high-pressure liquid chromatography (HPLC)-UV/visible spectroscopy method was developed and validated for simultaneous quantification of albendazole sulfoxide, albendazole sulfone, mebendazole, and oxantel pamoate in plasma. Albendazole, mebendazole, oxantel pamoate, albendazole-mebendazole, and albendazole-oxantel pamoate were orally applied to rats (100 mg/kg) and pharmacokinetic parameters calculated. CYP1A2 showed a 2.6-fold increased inhibition by albendazole-oxantel pamoate (50% inhibitory concentration [IC50] = 3.1 μM) and a 3.9-fold increased inhibition by albendazole sulfoxide-mebendazole (IC50 = 3.8 μM) compared to the single drugs. In rats, mebendazole's area under the concentration-time curve (AUC) and maximal plasma concentration (Cmax) were augmented 3.5- and 2.8-fold, respectively (P = 0.02 for both) when coadministered with albendazole compared to mebendazole alone. Albendazole sulfone was slightly affected by albendazole-mebendazole, displaying a 1.3-fold-elevated AUC compared to albendazole alone. Oxantel pamoate could not be quantified, translating to a bioavailability below 0.025% in rats. Elevated plasma levels of albendazole sulfoxide, albendazole sulfone, and mebendazole

  10. Enantioselective access to benzannulated spiroketals using a chiral sulfoxide auxiliary.

    PubMed

    Aitken, Harry R M; Furkert, Daniel P; Hubert, Jonathan G; Wood, James M; Brimble, Margaret A

    2013-08-21

    This article describes our efforts to develop an asymmetric synthesis of bisbenzannulated spiroketals using a chiral sulfoxide auxiliary. Our primary focus was on the synthesis of the 3H-spiro[benzofuran-2,2'-chroman] ring system, the spirocyclic core of the rubromycin family. Our strategy employed the use of lithium-halogen exchange on a racemic bromospiroketal in order to attach a chiral sulfoxide, thus producing two diastereomers. The diastereomers were separable, enabling isolation of each spiroketal enantiomer. Subsequent cleavage of the sulfoxide group from each diastereomer yielded the respective parent spiroketal in high enantiopurity.

  11. Pharmacokinetics of combined treatment with praziquantel and albendazole in neurocysticercosis

    PubMed Central

    Garcia, Hector H; Lescano, Andres G; Lanchote, Vera L; Pretell, E Javier; Gonzales, Isidro; Bustos, Javier A; Takayanagui, Osvaldo M; Bonato, Pierina S; Horton, John; Saavedra, Herbert; Gonzalez, Armando E; Gilman, Robert H

    2011-01-01

    AIMS Neurocysticercosis is the most common cause of acquired epilepsy in the world. Antiparasitic treatment of viable brain cysts is of clinical benefit, but current antiparasitic regimes provide incomplete parasiticidal efficacy. Combined use of two antiparasitic drugs may improve clearance of brain parasites. Albendazole (ABZ) has been used together with praziquantel (PZQ) before for geohelminths, echinococcosis and cysticercosis, but their combined use is not yet formally recommended and only scarce, discrepant data exist on their pharmacokinetics when given together. We assessed the pharmacokinetics of their combined use for the treatment of neurocysticercosis. METHODS A randomized, double-blind, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ and PZQ in 32 patients with neurocysticercosis was carried out. Patients received their usual concomitant medications including an antiepileptic drug, dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug (phenytoin or carbamazepine). Subjects had sequential blood samples taken after the first dose of antiparasitic drugs and again after 9 days of treatment, and were followed for 3 months after dosing. RESULTS Twenty-one men and 11 women, aged 16 to 55 (mean age 28) years were included. Albendazole sulfoxide concentrations were increased in the combination group compared with the ABZ alone group, both in patients taking phenytoin and patients taking carbamazepine. PZQ concentrations were also increased by the end of therapy. There were no significant side effects in this study group. CONCLUSIONS Combined ABZ + PZQ is associated with increased albendazole sulfoxide plasma concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect. PMID:21332573

  12. Processes to separate enantiomers.

    PubMed

    Lorenz, Heike; Seidel-Morgenstern, Andreas

    2014-01-27

    The provision of pure enantiomers is of increasing importance not only for the pharmaceutical industry but also for agrochemistry and biotechnology. In general, there are two rival approaches to provide pure enantiomers. The "chiral" approach is based on developing an asymmetric synthesis of just one of the enantiomers, while the "racemic" approach is based on separating mixtures of the two enantiomers. In the last few years remarkable progress has been achieved in the latter area. This Review focuses in particular on enantioselective crystallization processes and preparative chromatography, including hybrid processes and the incorporation of racemization steps. Several examples from our research are used for illustration purposes.

  13. Comparative plasma disposition of fenbendazole, oxfendazole and albendazole in dogs.

    PubMed

    Gokbulut, C; Bilgili, A; Hanedan, B; McKellar, Q A

    2007-09-30

    The plasma disposition of fenbendazole (FBZ), oxfendazole (OFZ) and albendazole (ABZ); and the enantiospecific disposition of OFZ, and ABZSO produced were investigated following an oral administration (50 mg/kg) in dogs. Blood samples were collected from 1 to 120 h post-administration. The plasma samples were analysed by high performance liquid chromatography (HPLC). The plasma concentration of FBZ, OFZ, ABZ and their metabolites were significantly different from each other and depended on the drug administered. The sulphone metabolite (FBZSO2) of FBZ was not detected in any plasma samples and the parent molecule ABZ did not reach quantifiable concentrations following FBZ and ABZ administration, respectively. OFZ and its sulphone metabolite attained a significantly higher plasma concentration and remained much longer in plasma compared with FBZ and ABZ and their respective metabolites. The maximum plasma concentrations (Cmax), area under the concentration time curve (AUC) and mean residence time (MRT) of parent OFZ were more than 30, 68 and 2 times those of FBZ, respectively. The same parameters for ABZSO were also significantly greater than those of FBZSO. The ratio for total AUCs of both the parent drug and the metabolites were 1:42:7 for following FBZ, OFZ and ABZ administration, respectively. The enantiomers were never in racemic proportions and (+) enantiomers of both OFZ and ABZSO were predominant in plasma. The AUC of (+) enantiomers of OFZ and ABZSO was, respectively more than three and seven times larger than that of (-) enantiomers of both molecules. It is concluded that the plasma concentration of OFZ was substantially greater compared with FBZ and ABZ. The data on the pharmacokinetic profile of OFZ presented here may contribute to evaluate its potential as an anthelmintic drug for parasite control in dogs.

  14. Triclabendazole Sulfoxide Causes Stage-Dependent Embryolethality in Zebrafish and Mouse In Vitro

    PubMed Central

    Boix, Nuria; Teixido, Elisabet; Vila-Cejudo, Marta; Ortiz, Pedro; Ibáñez, Elena; Llobet, Juan M.; Barenys, Marta

    2015-01-01

    Background Fascioliasis and paragonimiasis are widespread foodborne trematode diseases, affecting millions of people in more than 75 countries. The treatment of choice for these parasitic diseases is based on triclabendazole, a benzimidazole derivative which has been suggested as a promising drug to treat pregnant women and children. However, at the moment, this drug is not approved for human use in most countries. Its potential adverse effects on embryonic development have been scarcely studied, and it has not been assigned a pregnancy category by the FDA. Thus, to help in the process of risk-benefit decision making upon triclabendazole treatment during pregnancy, a better characterization of its risks during gestation is needed. Methodology The zebrafish embryo test, a preimplantation and a postimplantation rodent whole embryo culture were used to investigate the potential embryotoxicity/teratogenicity of triclabendazole and its first metabolite triclabendazole sulfoxide. Albendazole and albendazole sulfoxide were included as positive controls. Principal Findings Triclabendazole was between 10 and 250 times less potent than albendazole in inducing dysmorphogenic effects in zebrafish or postimplantation rodent embryos, respectively. However, during the preimplantation period, both compounds, triclabendazole and triclabendazole sulfoxide, induced a dose-dependent embryolethal effect after only 24 h of exposure in rodent embryos and zebrafish (lowest observed adverse effect concentrations = 10 μM). Conclusions/Significance In humans, after ingestion of the recommended doses of triclabendazole to treat fascioliasis and paragonimiasis (10 mg/kg), the main compound found in plasma is triclabendazole sulfoxide (maximum concentration 38.6 μM), while triclabendazole concentrations are approximately 30 times lower (1.16 μM). From our results it can be concluded that triclabendazole, at concentrations of the same order of magnitude as the clinically relevant ones, does

  15. Pharmacokinetics of azithromycin and the combination of ivermectin and albendazole when administered alone and concurrently in healthy volunteers.

    PubMed

    Amsden, Guy W; Gregory, Thomas B; Michalak, Cheryl A; Glue, Paul; Knirsch, Charles A

    2007-06-01

    Azithromycin is a critical component of an integrated disease elimination program against trachoma. This study was conducted to evaluate whether azithromycin has a pharmacokinetic interaction with the combination of ivermectin and albendazole. Eighteen healthy volunteers were administered single doses of azithromycin, ivermectin/albendazole, and the combination of the three agents in random, crossover fashion. To assess the presence of interactions, test (combination) and reference (single dose) data were compared using an estimation approach. Compared with reference phases, the geometric mean values for the combination arm's azithromycin AUC(0-t) and C(max) were increased approximately 13% and 20%, respectively, albendazole AUC(0-t) decreased by approximately 3% and C(max) increased approximately 3%, and ivermectin AUC(0-t) and C(max) were increased 31% and 27%, respectively. Albendazole sulfoxide AUC(0-t) and C(max) were decreased approximately 16% and 14%, respectively. All treatments were well tolerated. The interactions for azithromycin and albendazole were minimal although the increase in ivermectin exposure requires further study. PMID:17556628

  16. Enantioselective uptake of BOF-4272, a xanthine oxidase inhibitor with a chiral sulfoxide, by isolated rat hepatocytes.

    PubMed

    Naito, S; Nishimura, M

    2001-12-01

    The transport mechanisms of the enantiomers of BOF-4272, a new drug for the treatment of hyperuricemia, were studied using freshly prepared rat hepatocytes. BOF-4272 consists of S(-) and R(+) enantiomers due to a chiral center in the sulfoxide moiety. The uptake of these BOF-4272 enantiomers by hepatocytes was found to be temperature and dose dependent. The temperature-dependent uptake of the S(-) and R(+) enantiomers showed saturation kinetics. The Km values for the S(-) and R(+) enantiomers were 59.3 and 25.7 microM, respectively, which was a significant difference (p < 0.05). However, the maximal uptake rate was comparable for both enantiomers. Metabolic inhibitors such as antimycin, oligomycin, rotenone, carbonylcyanide m-chlorophenyl hydrazone, and carbonyl cyanide-p-(trifluromethoxy)-phenylhydrazone significantly inhibited uptake of the R(+) enantiomer, but had little effect on uptake of the S(-) enantiomer. Ouabain (an inhibitor of Na+/K(+)-ATPase) and p-nitrobenzylthioinosine (NBMPR, a nucleoside transporter inhibitor) showed no significant effects on the uptake of either enantiomer. Organic anions such as taurocholate and cholate reduced the uptake of both enantiomers. These results suggest that the hepatic uptake of both BOF-4272 enantiomers is not due to simple diffusion but also involves carrier-mediated uptake. We suggest that the carrier-mediated uptake of BOF-4272 enantiomers includes both NBMPR-insensitive facilitated diffusion and an active transport system in liver plasma membrane, and that the enantioselective uptake of BOF-4272 is due to differences in affinity for the active transporter.

  17. Albendazole

    MedlinePlus

    ... treat cystic hydatid disease (infection caused by the dog tapeworm in the liver, lung, and lining of ... breast-feeding.if you are having surgery, including dental surgery, tell the doctor or dentist that you ...

  18. ESR identification of gamma-irradiated albendazole

    NASA Astrophysics Data System (ADS)

    Çolak, Seyda

    2010-01-01

    The use of ionizing radiation for sterilization of pharmaceuticals is a well-established technology. In the present work, the spectroscopic and kinetic features of the radicals induced in gamma-irradiated solid albendazole samples is investigated at different temperatures in the dose range of 3-34 kGy by electron spin resonance (ESR) spectroscopy. Irradiation with gamma radiation produced two different radical species in albendazole. They were fairly stable at room temperature but relatively unstable above room temperature, giving rise to an unresolved ESR spectrum consisting of three resonance peaks centered at g=2.0057. Decay activation energies of the contributing radical species were calculated to be 47.8 (±13.5) and 50.5 (±9.7) kJ/mol using the signal intensity decay data derived from annealing studies performed at high temperatures. A linear function of the applied dose was found to best describe the experimental dose-response data. Albendazole does not present the characteristics of good dosimetric materials. However, the discrimination of irradiated albendazole from its unirradiated form was possible even 6 months after storage in normal conditions. Based on these findings, it is concluded that albendazole and albendazole-containing drugs can be safely sterilized by gamma radiation and that ESR spectroscopy could be successfully used as a potential technique for monitoring their radiosterilization.

  19. Determination of Albendazole and Metabolites in Silkworm Bombyx mori Hemolymph by Ultrafast Liquid Chromatography Tandem Triple Quadrupole Mass Spectrometry

    PubMed Central

    Li, Li; Xing, Dong-Xu; Li, Qing-Rong; Xiao, Yang; Ye, Ming-Qiang; Yang, Qiong

    2014-01-01

    Albendazole is a broad-spectrum parasiticide with high effectiveness and low host toxicity. No method is currently available for measuring albendazole and its metabolites in silkworm hemolymph. This study describes a rapid, selective, sensitive, synchronous and reliable detection method for albendazole and its metabolites in silkworm hemolymph using ultrafast liquid chromatography tandem triple quadrupole mass spectrometry (UFLC-MS/MS). The method is liquid-liquid extraction followed by UFLC separation and quantification in an MS/MS system with positive electrospray ionization in multiple reaction monitoring mode. Precursor-to-product ion transitions were monitored at 266.100 to 234.100 for albendazole (ABZ), 282.200 to 208.100 for albendazole sulfoxide (ABZSO), 298.200 to 159.100 for albendazole sulfone (ABZSO2) and 240.200 to 133.100 for albendazole amino sulfone (ABZSO2-NH2). Calibration curves had good linearities with R2 of 0.9905–0.9972. Limits of quantitation (LOQs) were 1.32 ng/mL for ABZ, 16.67 ng/mL for ABZSO, 0.76 ng/mL for ABZSO2 and 5.94 ng/mL for ABZSO2-NH2. Recoveries were 93.12%–103.83% for ABZ, 66.51%–108.51% for ABZSO, 96.85%–105.6% for ABZSO2 and 96.46%–106.14% for ABZSO2-NH2, (RSDs <8%). Accuracy, precision and stability tests showed acceptable variation in quality control (QC) samples. This analytical method successfully determined albendazole and its metabolites in silkworm hemolymph in a pharmacokinetic study. The results of single-dose treatment suggested that the concentrations of ABZ, ABZSO and ABZSO2 increased and then fell, while ABZSO2-NH2 level was low without obvious change. Different trends were observed for multi-dose treatment, with concentrations of ABZSO and ABZSO2 rising over time. PMID:25255321

  20. Therapy for neurocysticercosis.

    PubMed

    Takayanagui, Osvaldo Massaiti

    2004-01-01

    Therapy for neurocysticercosis has advanced during the last 20 years with the advent of albendazole (Zentel) and praziquantel (Cysticide). Albendazole is the current medication of choice for the treatment of neurocysticercosis and is recommended for symptomatic patients with multiple viable cysts in the brain parenchyma. Albendazole may also be useful in extraparenchymal cysticercosis, especially in the subarachnoid racemose form, when complete surgical resection of the cysts is usually impracticable. Currently, there is an intense debate over the value and safety of anticysticercal therapy. Causes for failure of anticysticercal therapy include high inter-individual variability in plasma concentration of albendazole sulfoxide and the complex interactions of several drugs with the albendazole metabolite. Furthermore, albendazole sulfoxide is an enantiomeric mixture of (+)- and (-)-albendazole sulfoxide with accumulation of the (+)-enantiomer in the cerebrospinal fluid. However, the question over which enantiomer is effective against cysticerci remains to be clarified.

  1. p-Chlorophenyl methyl sulfoxide

    Integrated Risk Information System (IRIS)

    p - Chlorophenyl methyl sulfoxide ; CASRN 934 - 73 - 6 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for

  2. A cell-based screen reveals that the albendazole metabolite, albendazole sulfone, targets Wolbachia.

    PubMed

    Serbus, Laura R; Landmann, Frederic; Bray, Walter M; White, Pamela M; Ruybal, Jordan; Lokey, R Scott; Debec, Alain; Sullivan, William

    2012-09-01

    Wolbachia endosymbionts carried by filarial nematodes give rise to the neglected diseases African river blindness and lymphatic filariasis afflicting millions worldwide. Here we identify new Wolbachia-disrupting compounds by conducting high-throughput cell-based chemical screens using a Wolbachia-infected, fluorescently labeled Drosophila cell line. This screen yielded several Wolbachia-disrupting compounds including three that resembled Albendazole, a widely used anthelmintic drug that targets nematode microtubules. Follow-up studies demonstrate that a common Albendazole metabolite, Albendazole sulfone, reduces intracellular Wolbachia titer both in Drosophila melanogaster and Brugia malayi, the nematode responsible for lymphatic filariasis. Significantly, Albendazole sulfone does not disrupt Drosophila microtubule organization, suggesting that this compound reduces titer through direct targeting of Wolbachia. Accordingly, both DNA staining and FtsZ immunofluorescence demonstrates that Albendazole sulfone treatment induces Wolbachia elongation, a phenotype indicative of binary fission defects. This suggests that the efficacy of Albendazole in treating filarial nematode-based diseases is attributable to dual targeting of nematode microtubules and their Wolbachia endosymbionts. PMID:23028321

  3. 21 CFR 556.34 - Albendazole.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....

  4. 21 CFR 556.34 - Albendazole.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....

  5. 21 CFR 556.34 - Albendazole.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....

  6. 21 CFR 556.34 - Albendazole.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....

  7. 21 CFR 556.34 - Albendazole.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... for albendazole 2-aminosulfone (marker residue) are: (1) Cattle—(i) Liver (target tissue): 0.2 parts per million (ppm). (ii) Muscle: 0.05 ppm. (2) Sheep—(i) Liver (target tissue): 0.25 ppm. (ii) Muscle: 0.05 ppm. (3) Goat—(i) Liver (target tissue): 0.25 ppm. (ii) (c) Related conditions of use....

  8. Efficacy of Albendazole-Chitosan Microsphere-based Treatment for Alveolar Echinococcosis in Mice.

    PubMed

    Abulaihaiti, Maitiseyiti; Wu, Xiang-Wei; Qiao, Lei; Lv, Hai-Long; Zhang, Hong-Wei; Aduwayi, Nasrul; Wang, Yan-Jie; Wang, Xin-Chun; Peng, Xin-Yu

    2015-01-01

    This study aimed to investigate the pharmacology and anti-parasitic efficacy of albendazole-chitosan microspheres (ABZ-CS-MPs) for established intraperitoneal infections of Echinococcus multilocularis metacestodes in an experimental murine model. Male outbred Kunming mice infected with E. multilocularis Metacestodes were administered with three ABZ formulations, namely, ABZ-CS-MPs, Liposome-Albendazole (L-ABZ), and albendazole tablet (ABZ-T). Each of the ABZ formulations was given orally at three different doses of 37.5, 75, and 150 mg/kg, three times a week for 12 weeks postinfection. After administering the drugs, we monitored the pharmacological performance and anti-parasitic efficacy of ABZ-CS-MPs compared with L-ABZ, and ABZ-T treated mice. ABZ-CS-MPs reduced the weight of tissues containing E. multilocularis metacestodes most effectively compared with the ABZ-T group and untreated controls. Metacestode grown was Highly suppressed during treatment with ABZ-CS-MPs. Significantly higher plasma levels of ABZ metabolites were measured in mice treated with ABZ-CS-MPs or L-ABZ compared with ABZ-T. In particular, enhanced ABZ-sulfoxide concentration profiles were observed in the mice given 150 mg/kg of ABZ-CS-MPs, but not in the mice treated with L-ABZ. Histological examination showed that damages caused disorganization of both the germinal and laminated layers of liver hyatid cysts, demolishing their characteristic structures after treatment with ABZ-CS-MPs or L-ABZ. Over time, ABZ-CS-MPs treatment induced a shift from Th2-dominant to Th1-dominant immune response. CS-MPs As a new carrier exhibited improved absorption and increased bioavailability of ABZ in the treatment of E. multilocularis infections in mice. PMID:26352932

  9. Albendazole-praziquantel interaction in healthy volunteers: kinetic disposition, metabolism and enantioselectivity

    PubMed Central

    Lima, Renata Monteiro; Ferreira, Maria Augusta Drago; de Jesus Ponte Carvalho, Teresa Maria; Dumêt Fernandes, Bruno José; Takayanagui, Osvaldo Massaiti; Garcia, Hector Hugo; Coelho, Eduardo Barbosa; Lanchote, Vera Lucia

    2011-01-01

    AIM This study investigated the kinetic disposition, metabolism and enantioselectivity of albendazole (ABZ) and praziquantel (PZQ) administered alone and in combination to healthy volunteers. METHODS A randomized crossover study was carried out in three phases (n = 9), in which some volunteers started in phase 1 (400 mg ABZ), others in phase 2 (1500 mg PZQ), and the remaining volunteers in phase 3 (400 mg ABZ + 1500 mg PZQ). Serial blood samples were collected from 0–48 h after drug administration. Pharmacokinetic parameters were calculated using a monocompartmental model with lag time and were analyzed using the Wilcoxon test; P≤ 0.05. RESULTS The administration of PZQ increased the plasma concentrations of (+)-ASOX (albendazole sulphoxide) by 264% (AUC 0.99 vs. 2.59 µg ml−1 h), (−)-ASOX by 358% (0.14 vs. 0.50 µg ml−1 h) and albendazole sulfone (ASON) by 187% (0.17 vs. 0.32 µg ml−1 h). The administration of ABZ did not change the kinetic disposition of (+)-(S)-PZQ (–)-(R)-4-OHPZQ or (+)-(S)-4-OHPZQ, but increased the plasma concentration of (–)-(R)-PZQ by 64.77% (AUC 0.52 vs. 0.86 µg ml−1 h). CONCLUSIONS The pharmacokinetic interaction between ABZ and PZQ in healthy volunteers was demonstrated by the observation of increased plasma concentrations of ASON, both ASOX enantiomers and (–)-(R)-PZQ. Clinically, the combination of ABZ and PZQ may improve the therapeutic efficacy as a consequence of higher concentration of both active drugs. On the other hand, the magnitude of this elevation may represent an increased risk of side effects, requiring, certainly, reduction of the dosage. However, further studies are necessary to evaluate the efficacy and safety of this combination. PMID:21395645

  10. Selenium and Methionine Sulfoxide Reduction.

    PubMed

    Gladyshev, Vadim N

    2014-10-01

    Selenium is an essential trace element because it is present in proteins in the form of selenocysteine residue. Functionally characterized selenoproteins are oxidoreductases. Selenoprotein methionine-R-sulfoxide reductase B1 (MsrB1) is a repair enzyme that reduces ROS-oxidized methionine residues in proteins. Here, we explored a possibility that reversible methionine oxidation is also a mechanism that regulates protein function. We found that MsrB1, together with Mical proteins, regulated mammalian actin assembly via stereospecific methionine oxidation and reduction in a reversible, site-specific manner. Two methionine residues in actin were specifically converted to methionine-R-sulfoxide by Mical1 and Mical2 and reduced back to methionine by MsrB1, supporting actin disassembly and assembly, respectively. Macrophages utilized this redox control during cellular activation by stimulating MsrB1 expression and activity. Thus, we identified the regulatory role of MsrB1 as a Mical antagonist in orchestrating actin dynamics and macrophage function. More generally, our study showed that proteins can be regulated by reversible site-specific methionine-R-sulfoxidation and that selenium is involved in this regulation by being a catalytic component of MsrB1. PMID:26461418

  11. 21 CFR 520.45 - Albendazole oral dosage forms.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Albendazole oral dosage forms. 520.45 Section 520.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.45 Albendazole...

  12. 21 CFR 520.45 - Albendazole oral dosage forms.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Albendazole oral dosage forms. 520.45 Section 520.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.45 Albendazole...

  13. 21 CFR 520.45 - Albendazole oral dosage forms.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Albendazole oral dosage forms. 520.45 Section 520.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.45 Albendazole...

  14. 21 CFR 520.38 - Albendazole oral dosage forms.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Albendazole oral dosage forms. 520.38 Section 520.38 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.38 Albendazole...

  15. 21 CFR 520.45 - Albendazole oral dosage forms.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Albendazole oral dosage forms. 520.45 Section 520.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.45 Albendazole...

  16. Albendazole inhibits Pneumocystis carinii proliferation in inoculated immunosuppressed mice.

    PubMed Central

    Bartlett, M S; Edlind, T D; Lee, C H; Dean, R; Queener, S F; Shaw, M M; Smith, J W

    1994-01-01

    Albendazole, a benzimidazole derivative widely used for treating helminth infections, was successfully used to treat and prevent development of Pneumocystis carinii pneumonia in transtracheally inoculated immunosuppressed mice. For treatment, 3 weeks postinoculation, albendazole at 300 and 600 mg/kg of body weight per day was administered in food for 3 weeks. For prophylaxis, albendazole was begun on the same day as inoculation at 300 mg/kg/day for 7 days, and then the dose was reduced to 150 mg/kg/day for 35 additional days. With these regimens, albendazole was effective both for treatment and prophylaxis. Both dexamethasone-immunosuppressed and L3T4+ monoclonal antibody-immunosuppressed mouse models were used, and albendazole inhibited P. carinii infection in both. PMID:7986016

  17. Neurocysticercosis with Diplopia Responds Well to Albendazole.

    PubMed

    Sato, Akihiro; Nakamura, Itaru; Fujita, Hiroaki; Fukushima, Shinji; Mizuno, Yasutaka; Fujii, Takeshi; Matsumoto, Tetsuya

    2016-01-01

    We report a case of neurocysticercosis concurrent with taeniasis in a 31-year-old woman. The patient presented with a headache and diplopia. Oculomotor disturbances with a left adduction deficit were observed. Fundoscopy revealed papilledema. Additionally, computed tomography of the brain revealed more than 20 small cysts within the parenchyma, most of which were associated with ring enhancement. Moreover, serum antibody testing (Western blotting) for Taenia solium-cysticerci was positive. The patient received albendazole and corticosteroids, and progressive resolution of the neurological symptoms and papilledema was observed starting approximately three days after administration. This patient has been asymptomatic for more than one year. PMID:27150884

  18. Efficacy of Albendazole-Chitosan Microsphere-based Treatment for Alveolar Echinococcosis in Mice

    PubMed Central

    Abulaihaiti, Maitiseyiti; Wu, Xiang-Wei; Qiao, Lei; Lv, Hai-Long; Zhang, Hong-Wei; Aduwayi, Nasrul; Wang, Yan-Jie

    2015-01-01

    This study aimed to investigate the pharmacology and anti-parasitic efficacy of albendazole–chitosan microspheres (ABZ-CS-MPs) for established intraperitoneal infections of Echinococcus multilocularis metacestodes in an experimental murine model. Male outbred Kunming mice infected with E. multilocularis Metacestodes were administered with three ABZ formulations, namely, ABZ-CS-MPs, Liposome–Albendazole (L-ABZ), and albendazole tablet (ABZ-T). Each of the ABZ formulations was given orally at three different doses of 37.5, 75, and 150mg/kg, three times a week for 12 weeks postinfection. After administering the drugs, we monitored the pharmacological performance and anti-parasitic efficacy of ABZ-CS-MPs compared with L-ABZ, and ABZ-T treated mice. ABZ-CS-MPs reduced the weight of tissues containing E. multilocularis metacestodes most effectively compared with the ABZ-T group and untreated controls. Metacestode grown was Highly suppressed during treatment with ABZ-CS-MPs. Significantly higher plasma levels of ABZ metabolites were measured in mice treated with ABZ-CS-MPs or L-ABZ compared with ABZ-T. In particular, enhanced ABZ-sulfoxide concentration profiles were observed in the mice given 150mg/kg of ABZ-CS-MPs, but not in the mice treated with L-ABZ. Histological examination showed that damages caused disorganization of both the germinal and laminated layers of liver hyatid cysts, demolishing their characteristic structures after treatment with ABZ-CS-MPs or L-ABZ. Over time, ABZ-CS-MPs treatment induced a shift from Th2-dominant to Th1-dominant immune response. CS-MPs As a new carrier exhibited improved absorption and increased bioavailability of ABZ in the treatment of E. multilocularis infections in mice. PMID:26352932

  19. Chemoenzymatic Synthesis of Proxyphylline Enantiomers.

    PubMed

    Borowiecki, Paweł; Paprocki, Daniel; Dudzik, Agnieszka; Plenkiewicz, Jan

    2016-01-15

    A novel synthetic route for preparation of proxyphylline enantiomers using a kinetic resolution (KR) procedure as the key step is presented. The reactions were catalyzed by immobilized Candida antarctica lipase B in acetonitrile. Three types of reactions were examined: (i) enantioselective transesterification of racemic proxyphylline with vinyl acetate as well as (ii) hydrolysis and (iii) methanolysis of its esters. The influence of reaction conditions on the substrate conversion and enantiomeric purity of the products were investigated. Studies on analytical scale reactions revealed that the titled API enantiomers could be successfully obtained with excellent enantiomeric excess (up to >99% ee). The process was easily conducted on a 5 g scale at 100 g/L. In a preparative-scale reaction, unreacted (S)-(+)-butanoate (97% ee) and (R)-(-)-alcohol (96% ee) were obtained after 2 days in yields of 45% and 46%, respectively. When the reaction time was extended to 6 days, (S)-(+)-butanoate was isolated in >99% ee and acceptable high enantioselectivity (E = 90). Importantly, the KR's products could be conveniently isolated by exploiting varying solubility of the ester/alcohol in acetonitrile at room temperature. In addition, a chiral preference of the CAL-B active site for the R-enantiomer was rationalized by in sillico docking studies. PMID:26517306

  20. Sensitive in vitro system to assess morphological and biochemical effects of praziquantel and albendazole on Taenia solium cysts.

    PubMed

    Mahanty, S; Paredes, A; Marzal, M; Gonzalez, E; Rodriguez, S; Dorny, P; Guerra-Giraldez, C; Garcia, H H; Nash, T

    2011-01-01

    Neurocysticercosis resulting from Taenia solium infections is a major cause of adult-acquired seizures worldwide. Disease is caused by larval cysts, and treatment consists of the anthelmintic drugs albendazole or praziquantel. There are no standard methods to assess drug activity to T. solium cysts in vitro. Morphological, functional, and biochemical changes that might reflect damaging (inhibiting, cytotoxic) drug effects were analyzed after exposure of cysts to albendazole sulfoxide (ABZ-SO), the major active metabolite of the drug in vivo, praziquantel (PZQ), or combinations of both. PZQ exposure led to a decrease in cyst size and inhibition of evagination, whereas ABZ-SO exposure resulted in minimal changes. Alkaline phosphatase (AP) is normally secreted by cysts, and both drugs inhibited AP secretion at concentrations of 5 and 50 ng/ml for PZQ and ABZ-SO, respectively. Some combinations of both drugs resulted in additive and/or synergistic activities. Parasite-specific antigen, detected in the cerebrospinal fluid and blood of infected patients, is also normally secreted by T. solium cysts. Antigen secretion was similarly inhibited by ABZ-SO and PZQ and a combination of both drugs, suggesting that inhibition of secretion is a common downstream consequence of the activities of both drugs. These studies establish quantitative methods to measure in vitro anthelmintic activity and suggest combination therapy with ABZ-SO and PZQ may have clinical benefit. PMID:21041508

  1. CYP2J2 and CYP2C19 are the major enzymes responsible for metabolism of albendazole and fenbendazole in human liver microsomes and recombinant P450 assay systems.

    PubMed

    Wu, Zhexue; Lee, Doohyun; Joo, Jeongmin; Shin, Jung-Hoon; Kang, Wonku; Oh, Sangtaek; Lee, Do Yup; Lee, Su-Jun; Yea, Sung Su; Lee, Hye Suk; Lee, Taeho; Liu, Kwang-Hyeon

    2013-11-01

    Albendazole and fenbendazole are broad-spectrum anthelmintics that undergo extensive metabolism to form hydroxyl and sulfoxide metabolites. Although CYP3A and flavin-containing monooxygenase have been implicated in sulfoxide metabolite formation, the enzymes responsible for hydroxyl metabolite formation have not been identified. In this study, we used human liver microsomes and recombinant cytochrome P450s (P450s) to characterize the enzymes involved in the formation of hydroxyalbendazole and hydroxyfenbendazole from albendazole and fenbendazole, respectively. Of the 10 recombinant P450s, CYP2J2 and/or CYP2C19 was the predominant enzyme catalyzing the hydroxylation of albendazole and fenbendazole. Albendazole hydroxylation to hydroxyalbendazole is primarily mediated by CYP2J2 (0.34 μl/min/pmol P450, which is a rate 3.9- and 8.1-fold higher than the rates for CYP2C19 and CYP2E1, respectively), whereas CYP2C19 and CYP2J2 contributed to the formation of hydroxyfenbendazole from fenbendazole (2.68 and 1.94 μl/min/pmol P450 for CYP2C19 and CYP2J2, respectively, which are rates 11.7- and 8.4-fold higher than the rate for CYP2D6). Correlation analysis between the known P450 enzyme activities and the rate of hydroxyalbendazole and hydroxyfenbendazole formation in samples from 14 human liver microsomes showed that albendazole hydroxylation correlates with CYP2J2 activity and fenbendazole hydroxylation correlates with CYP2C19 and CYP2J2 activities. These findings were supported by a P450 isoform-selective inhibition study in human liver microsomes. In conclusion, our data for the first time suggest that albendazole hydroxylation is primarily catalyzed by CYP2J2, whereas fenbendazole hydroxylation is preferentially catalyzed by CYP2C19 and CYP2J2. The present data will be useful in understanding the pharmacokinetics and drug interactions of albendazole and fenbendazole in vivo.

  2. Abdominal Cystic Echinococcosis Treated with Albendazole. A Pediatric Cohort Study

    PubMed Central

    Moroni, Samanta; Moscatelli, Guillermo; Bournissen, Facundo García; González, Nicolás; Ballering, Griselda; Freilij, Héctor; Salgueiro, Fabián; Altcheh, Jaime

    2016-01-01

    Introduction Cystic echinococcosis is endemic in Argentina. The standard pharmacological treatment for the disease is albendazole, but surgery is a common alternative. Even though primary infection occurs mainly in the pediatric population, the optimal therapeutic option in pediatrics is not clearly defined and few pediatric cohorts with cystic echinococcosis treated with albendazole have been described to date. Objective To describe therapeutic response to albendazole in a cohort of pediatric patients with abdominal cystic echinococcosis. Population and Methods Patients (0–18 years old) with abdominal cystic echinococcosis who were treated with albendazole between January 1998 and August 2013. Diagnosis of abdominal cystic echinococcosis was made by ultrasound. All patients received albendazole, 10–15 mg/kg/day. Epidemiological data, symptoms, number, location and outcome of the cysts, serology and treatment received were analyzed. The parameter used to assess treatment response was cyst changes evaluated by ultrasound follow up using the WHO-IWGE classification. Results A total of 28 patients (with 46 abdominal cysts) were included in the cohort. Mean age at enrolment was 9.4 years and mean duration of follow-up, 23.8 months. All patients resided in rural areas and had had contact with dogs. The asymptomatic form of the disease was the most common presentation. All patients received albendazole (mean duration: 142.5 days), with low incidence of adverse events. Albendazole had a positive effect on most of the cysts. Surgery was performed in 13 patients. Conclusion Treatment with albendazole for uncomplicated cystic echinococcosis cysts is safe and effective, and can potentially reduce the need for surgical intervention. PMID:27589236

  3. Enantiomer Separations by Capillary Electrophoresis.

    PubMed

    Scriba, Gerhard K E; Harnisch, Henrik; Zhu, Qingfu

    2016-01-01

    Capillary electrophoresis (CE) is a versatile and flexible technique for analytical enantioseparations. This is due to the large variety of chiral selectors as well as the different operation modes including electrokinetic chromatography, micellar electrokinetic chromatography, and microemulsion electrokinetic chromatography. The chiral selector, which is added to the background electrolyte, represents a pseudostationary phase with its own electrophoretic mobility allowing a variety of different separation protocols. The present chapter briefly addresses the basic fundamentals of CE enantioseparations as well as the most frequently applied chiral selectors and separation modes. The practical example illustrates the separation of the enantiomers of a positively charged analyte using native and charged cyclodextrin derivatives as chiral selectors. PMID:27645742

  4. Meroterpenoid enantiomers from Ganoderma sinensis.

    PubMed

    Cao, Wen-Wen; Luo, Qi; Cheng, Yong-Xian; Wang, Shu-Mei

    2016-04-01

    Zizhines A-F (1-6), six pairs of new meroterpenoid enantiomers and a known meroterpenoid (7) were isolated from the fruiting bodies of Ganoderma sinensis. The structures and absolute configurations of the new substances were assigned by spectroscopic and computational methods. All the compounds apart from 7 were evaluated for their inhibition on extracellular matrix component (fibronectin) generation by using TGF-β1-induced rat kidney tubular epithelial cells. Although none of them was found to be active in these cells, the present findings add new facets for the chemistry of Ganoderma. PMID:26947249

  5. Meroterpenoid enantiomers from Ganoderma sinensis.

    PubMed

    Cao, Wen-Wen; Luo, Qi; Cheng, Yong-Xian; Wang, Shu-Mei

    2016-04-01

    Zizhines A-F (1-6), six pairs of new meroterpenoid enantiomers and a known meroterpenoid (7) were isolated from the fruiting bodies of Ganoderma sinensis. The structures and absolute configurations of the new substances were assigned by spectroscopic and computational methods. All the compounds apart from 7 were evaluated for their inhibition on extracellular matrix component (fibronectin) generation by using TGF-β1-induced rat kidney tubular epithelial cells. Although none of them was found to be active in these cells, the present findings add new facets for the chemistry of Ganoderma.

  6. Nicotine enantiomers and oxidative stress.

    PubMed

    Yildiz, D; Ercal, N; Armstrong, D W

    1998-09-15

    Nicotine affects a variety of cellular processes ranging from induction of gene expression to secretion of hormones and modulation of enzymatic activities. The objective of this study was to characterize the toxicity of nicotine enantiomers as well as their ability to induce oxidative stress in an in vitro model using Chinese hamster ovary (CHO) cells. Colony formation assay has demonstrated that (-)-nicotine is the more toxic of the enantiomers. At 6 mM concentrations, (-)-nicotine was found to be approximately 28- and 19-fold more potent than (+)-, and (+/-)-nicotine (racemic), respectively. Results also indicated that the toxicity of (+/-)-nicotine is higher than that of (+)-nicotine. (-)-Nicotine at a 10 mM concentration substantially decreased glutathione (GSH) levels (46% decrease). In addition, a 3-fold increase in malondialdehyde (MDA) level was evident in cells after exposure to 10 mM (-)-nicotine. Increased lactate dehydrogenase (LDH) activities in the media demonstrated that cellular membrane integrity was disturbed in nicotine treated cells. In the presence of superoxide dismutase (SOD) and catalase (CAT), the LDH activities returned to control value in 24 h with all concentrations of (-)-, (+)-, and (+/-)-nicotine. The decreases in LDH activities in the presence of the radical scavenging enzymes SOD and CAT suggest that membrane damage may be due to free radical generation. PMID:9865482

  7. Metabolic profiling of praziquantel enantiomers

    PubMed Central

    Wang, Haina; Fang, Zhong-Ze; Zheng, Yang; Zhou, Kun; Hu, Changyan; Krausz, Kristopher W; Sun, Dequn; Idle, Jeffrey R.; Gonzalez, Frank J

    2014-01-01

    Praziquantel (PZQ), prescribed as a racemic mixture, is the most readily available drug to treat schistosomiasis. In the present study, ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) based metabolomics was employed to decipher the metabolic pathways and enantioselective metabolic differences of PZQ. Many phase I and four new phase II metabolites were found in urine and feces samples of mice 24h after dosing indicating that the major metabolic reaction encompassed oxidation, dehydrogenation, and glucuronidation. Differences in the formation of all these metabolites were observed between (R)-PZQ and (S)-PZQ. In an in vitro phase I incubation system, the major involvement of CYP3A, CYP2C9, and CYP2C19 in the metabolism of PZQ, and CYP3A, CYP2C9, and CYP2C19 exhibited different catalytic activity towards the PZQ enantiomers. Apparent Km and Vmax differences were observed in the catalytic formation of three mono-oxidized metabolites by CYP2C9 and CYP3A4 further supporting the metabolic differences for PZQ enantiomers. Molecular docking showed that chirality resulted in differences in location and conformation, which likely accounts for the metabolic differences. In conclusion, in silico, in vitro, and in vivo methods revealed the enantioselective metabolic profile of praziquantel. PMID:24821110

  8. Spasmolytic Activity of Carvone and Limonene Enantiomers.

    PubMed

    de Sousa, Damião Pergentino; Mesquita, Rafael Ferreira; de Araújo Ribeiro, Luciano Augusto; de Lima, Julianeli Tolentino

    2015-11-01

    Aromatic plants produce volatile substances with high therapeutic potential. In view of the need for new respiratory and cardiovascular system pharmacological agents, the present study reports on the spasmolytic activity of two enantiomers of carvone and limonene, constituents of essential oils. The enantiomers tested showed pharmacological activity in Guinea pig trachea and rat aorta smooth muscle. No differences were observed in the pharmacological profiles of the enantiomer pairs. The oxygenated monoterpenes (+)-carvone and (-)-carvone were pharmacologically more effective than the hydrocarbon monoterpenes (+)-limonene and (-)-limonene. The results of this study show the therapeutic potential of these compounds found in many aromatic plants for the treatment of respiratory and cardiovascular system diseases.

  9. Oral albendazole in the management of extraocular cysticercosis.

    PubMed Central

    Sihota, R; Honavar, S G

    1994-01-01

    Surgical removal of extraocular cysticerci is fraught with complications. The effect of oral albendazole in such cases has been evaluated in a randomised, controlled, clinical trial. Of 24 ultrasonographically diagnosed, and ELISA positive cases of extraocular cysticerci, 12 received oral albendazole 15 mg/kg once daily for 1 month, while the 12 controls received a placebo. Marked clinical improvement was seen in all the cases in the treatment group at 4 weeks, with collapse of the cyst at 6 weeks (75%), and complete disappearance at 3 months (100%). No clinical or ultrasonographical change was noted in the control group. A trial of medical management with oral albendazole merits consideration in cases of extraocular cysticerci. Images PMID:7918290

  10. ENANTIOMER-SPECIFIC EFFECTS OF CHIRAL POLLUTANTS

    EPA Science Inventory

    Enantiomers, the mirror image isomers of chiral pollutants, are known to be selective in their interaction with other chiral molecules, including enzymes and other biochemicals. Considerable research has shown, for example, that chiral pesticides are degraded selectively by micr...

  11. Deoxidation of fenthion sulfoxide, fenthion oxon sulfoxide and fensulfothion in gas chromatograph/mass spectrometer, and the prevention of sulfoxide deoxidation by polyethylene glycol 300.

    PubMed

    Sugitate, Kuniyo; Yamagami, Takashi; Nakamura, Sadao; Toriba, Akira; Hayakawa, Kazuichi

    2012-01-01

    Fenthion, fenthion sulfoxide, fenthion oxon sulfoxide and fensulfothion showed two different mass spectra in GC/MS, depending on their concentrations. The base peaks shifted to lower levels by 1 m/z at lower concentration, and no retention time shifts were observed. The "shifted base peaks" were not obtained by a general EI fragmentation. The product ion scan spectra of the "shifted base peaks" were coincident with those of molecular ions of their corresponding sulfides. These phenomena can be ascribed to the conversion of sulfoxide into sulfide by the dominant deoxidation reaction than EI fragmentation in an ion source. Adding polyethylene glycol 300 (PEG300) into a test solution prevented sulfoxide deoxidation.

  12. Cysteine sulfoxide derivatives in Petiveria alliacea.

    PubMed

    Kubec, R; Musah, R A

    2001-11-01

    Two diastereomers of S-benzyl-L-cysteine sulfoxide have been isolated from fresh roots of Petiveria alliacea. Their structures and absolute configurations have been determined by NMR, MALDI-HRMS, IR and CD spectroscopy and confirmed by comparison with authentic compounds. Both the R(S) and S(S) diastereomers of the sulfoxide are present in all parts of the plant (root, stem, and leaves) with the latter diastereomer being predominant. Their total content greatly varied in different parts of the plant between 0.07 and 2.97 mg g(-1) fr. wt, being by far the highest in the root. S-Benzylcysteine has also been detected in trace amounts (<10 microg g(-1) fr. wt) in all parts of the plant. This represents the first report of the presence of S-benzylcysteine derivatives in nature.

  13. Enantiomer Ratios of Meteoritic Sugar Derivatives

    NASA Technical Reports Server (NTRS)

    Cooper, George

    2012-01-01

    Carbonaceous meteorites contain a diverse suite of soluble organic compounds. Studies of these compounds reveal the Solar System's earliest organic chemistry. Among the classes of organic compounds found in meteorites are keto acids (pyruvic acid, etc.), hydroxy tricarboxylic acids (1), amino acids, amides, purines and pyrimidines. The Murchison and Murray meteorites are the most studied for soluble and insoluble organic compounds and organic carbon phases. The majority of (indigenous) meteoritic compounds are racemic, (i.e., their D/L enantiomer ratios are 50:50). However, some of the more unusual (non-protein) amino acids contain slightly more of one enantiomer (usually the L) than the other. This presentation focuses on the enantiomer analyses of three to six-carbon (3C to 6C) meteoritic sugar acids. The molecular and enantiomer analysis of corresponding sugar alcohols will also be discussed. Detailed analytical procedures for sugar-acid enantiomers have been described. Results of several meteorite analyses show that glyceric acid is consistently racemic (or nearly so) as expected of non-biological mechanisms of synthesis. Also racemic are 4-C deoxy sugar acids: 2-methyl glyceric acid; 2,4-dihydroxybutyric acid; 2,3-dihydroxybutyric acid (two diastereomers); and 3,4-dihydroxybutyric acid. However, a 4C acid, threonic acid, has never been observed as racemic, i.e., it possesses a large D excess. In several samples of Murchison and one of GRA 95229 (possibly the most pristine carbonaceous meteorite yet analyzed) threonic acid has nearly the same D enrichment. In Murchison, preliminary isotopic measurements of individual threonic acid enantiomers point towards extraterrestrial sources of the D enrichment. Enantiomer analyses of the 5C mono-sugar acids, ribonic, arabinonic, xylonic, and lyxonic also show large D excesses. It is worth noting that all four of these acids (all of the possible straight-chained 5C sugar acids) are present in meteorites, including the

  14. Stereospecific synthesis of m-Hydroxymexiletine enantiomers.

    PubMed

    Catalano, Alessia; Carocci, Alessia; Lentini, Giovanni; Defrenza, Ivana; Bruno, Claudio; Franchini, Carlo

    2012-09-01

    m-Hydroxymexiletine (MHM) is a metabolite of mexiletine, a well known class IB anti-arrhythmic drug, which presents almost twice the activity of the parent compound on cardiac voltage-gated sodium channels. Given the different activity of mexiletine enantiomers on sodium currents (being the R-isomer the eutomer), it is conceivable that (R)- and(S)-MHM could differ in pharmacodynamic and pharmacokinetic properties, too. Herein we report the efficient synthesis of MHM enantiomers that could represent useful tools for further investigations on stereospecific requirements of the voltage-gated sodium channel binding site. MHM enantiomers and all the homochiral intermediates were fully characterized. The ee values for (R)- and (S)-MHM were >99%, as assessed by capillary electrophoresis using β-cyclodextrin sulfated sodium salt as a chiral selector. PMID:23140556

  15. Revisiting optical clearing with dimethyl sulfoxide (DMSO)

    PubMed Central

    Bui, Albert K.; McClure, R. Anthony; Chang, Jennell; Stoianovici, Charles; Hirshburg, Jason; Yeh, Alvin T.; Choi, Bernard

    2009-01-01

    Functional optical characterization of disease progression and response to therapy suffers from loss of spatial resolution and imaging depth due to scattering. Here we report on the ability of dimethyl sulfoxide (DMSO) alone to reduce the optical scattering of skin. We observed a three-fold reduction in the scattering of skin with topical DMSO application. With an in vivo window chamber model, we observed a three-fold increase in light transmittance through the preparation and enhanced visualization of subsurface microvasculature. Collectively, our data demonstrate the potential of DMSO alone to mitigate effects of scattering, which we expect will improve molecular imaging studies. PMID:19226579

  16. Two new bicyclic sulfoxides from Welsh onion.

    PubMed

    Nohara, Toshihiro; Fujiwara, Yukio; Ikeda, Tsuyoshi; Murakami, Kotaro; Ono, Masateru; El-Aasr, Mona; Nakano, Daisuke; Kinjo, Junei

    2016-04-01

    Newly identified bicyclic sulfoxides, welsonins A1 (1) and A2 (2), were isolated from acetone extracts of the bulbs of the Welsh onion (Allium fistulosum). In this study, the structures of 1 and 2, which are tetrahydrothiophene-S-oxide derivatives, were characterized by spectroscopic analysis. These compounds appeared to be derived from the coupling of 1-propenyl sulfenic acid and uronic acid. Welsonin A1 (1) showed the potential to suppress tumor-cell proliferation by inhibiting the polarization of alternatively activated M2 macrophages.

  17. Two new bicyclic sulfoxides from Welsh onion.

    PubMed

    Nohara, Toshihiro; Fujiwara, Yukio; Ikeda, Tsuyoshi; Murakami, Kotaro; Ono, Masateru; El-Aasr, Mona; Nakano, Daisuke; Kinjo, Junei

    2016-04-01

    Newly identified bicyclic sulfoxides, welsonins A1 (1) and A2 (2), were isolated from acetone extracts of the bulbs of the Welsh onion (Allium fistulosum). In this study, the structures of 1 and 2, which are tetrahydrothiophene-S-oxide derivatives, were characterized by spectroscopic analysis. These compounds appeared to be derived from the coupling of 1-propenyl sulfenic acid and uronic acid. Welsonin A1 (1) showed the potential to suppress tumor-cell proliferation by inhibiting the polarization of alternatively activated M2 macrophages. PMID:26676612

  18. Albendazole-induced liver injury: a case report.

    PubMed

    Ríos, David; Restrepo, Juan C

    2013-04-01

    We report a case of a 47-year-old male, who was referred to the clinical hepatology services at Pablo Tobón Uribe Hospital for evaluation of a jaundice syndrome. After undergoing several exams, we diagnosed hepatic hydatidosis and the patient was treated with albendazole; however, after five months of uninterrupted treatment the patient again consulted and his liver test showed marked hepatocellular damage. This time, the patient was diagnosed with drug-induced liver injury due to albendazole, based on information from the clinical record, history of drug consumption, clinical and laboratory tests improved after discontinuing the medication and after discarding other possible causes; this diagnosis was supported by the CIOMS/RUCAM scale, which showed a "likely" correlation between hepatocellular damage and drug toxicity etiology.

  19. [Synthesis of metabolites and enantiomers of prolintane].

    PubMed

    Rücker, G; Neugebauer, M; Zhong, D

    1992-01-01

    The synthesis of 15 possible metabolites of prolintane (1) (Katovit) which is used in the treatment of blood pressure disregulations is described. Furthermore, the preparation of the enantiomers of 1 is reported, starting with R-(+)- and S-(-)-phenylalaninol respectively. PMID:1605711

  20. Preparative resolution of etodolac enantiomers by preferential crystallization method.

    PubMed

    Dung, Phan Thanh; Trung, Tran Quoc; Kim, Kyeong Ho

    2009-10-01

    Pure enantiomers are of large interest for several industries. This study was aimed to establish a method for separation of etodolac enantiomers by preferential crystallization after a conglomerate formation of its derivatives. S-(+)-etodolac and R-(-)-etodolac enantiomers were both prepared by classical resolution via crystallization of diastereoisomeric salt with (-)-brucine and (-)-cinchonidine. Enantiomeric purity of etodolac was determined by HPLC method using Chiralcel OD-H column. The pure diastereomeric salt collected from repeated recrystallization was further fractionated by liquid-liquid extraction to pure enantiomers. Etodolac enantiomers were recovered with overall yield more than 20% and the purities were over 99.9%.

  1. Determination of lansoprazole enantiomers in dog plasma by column-switching liquid chromatography with tandem mass spectrometry and its application to a preclinical pharmacokinetic study.

    PubMed

    Wang, Hao; Sun, Yantong; Meng, Xiangjun; Yang, Bo; Wang, Jian; Yang, Yan; Gu, Jingkai

    2015-09-01

    Lansoprazole, a selective proton pump inhibitor, has a chiral benzimidazole sulfoxide structure and is used for the treatment of gastric acid hypersecretory related diseases. To investigate its stereoselective pharmacokinetics, a column-switching liquid chromatography with tandem mass spectrometry method was developed for the determination of lansoprazole enantiomers in dog plasma using (+)-pantoprazole as an internal standard. After a simple protein precipitation procedure with acetonitrile, matrix components left behind after sample preparation were further eliminated from the sample by reversed-phase chromatography on a C18 column. The fluent was fed to a chiral column for the separation of lansoprazole enantiomers. Baseline separation of lansoprazole enantiomers was achieved on a Chiralcel OZ-RH column using acetonitrile/0.1% formic acid in water (35:65, v/v) as the mobile phase at 40°C. The linearity of the calibration curves ranged from 3 to 800 ng/mL for each enantiomer. Intra- and inter-day precisions ranged from 2.1 to 7.3% with an accuracy of ±1.7% for (+)-lansoprazole, and from 1.6 to 6.9% with an accuracy of ±3.5% for (-)-lansoprazole, respectively. The validated method was successfully applied for the stereoselective pharmacokinetic study of lansoprazole in beagle dog after intravenous infusion.

  2. Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection

    PubMed Central

    Henriquez-Camacho, Cesar; Gotuzzo, Eduardo; Echevarria, Juan; White, A Clinton; Terashima, Angelica; Samalvides, Frine; Pérez-Molina, José A; Plana, Maria N

    2016-01-01

    Background Strongyloidiasis is a gut infection with Strongyloides stercoralis which is common world wide. Chronic infection usually causes a skin rash, vomiting, diarrhoea or constipation, and respiratory problems, and it can be fatal in people with immune deficiency. It may be treated with ivermectin or albendazole or thiabendazole. Objectives To assess the effects of ivermectin versus benzimidazoles (albendazole and thiabendazole) for treating chronic strongyloides infection. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register (24 August 2015); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (January 1966 to August 2015); EMBASE (January 1980 to August 2015); LILACS (August 2015); and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) using 'strongyloid*' as a search term, reference lists, and conference abstracts. Selection criteria Randomized controlled trials of ivermectin versus albendazole or thiabendazole for treating chronic strongyloides infection. Data collection and analysis Two review authors independently extracted data and assessed risk of bias in the included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) and fixed- or random-effects models. We pooled adverse event data if the trials were sufficiently similar in their adverse event definitions. Main results We included seven trials, enrolling 1147 participants, conducted between 1994 and 2011 in different locations (Africa, Southeast Asia, America and Europe). In trials comparing ivermectin with albendazole, parasitological cure was higher with ivermectin (RR 1.79, 95% CI 1.55 to 2.08; 478 participants, four trials, moderate quality evidence). There were no statistically significant differences in adverse events (RR 0.80, 95% CI 0.59 to 1.09; 518 participants, four trials, low quality evidence). In trials comparing ivermectin with thiabendazole

  3. Efficacy of pharmacokinetic interactions between piperonyl butoxide and albendazole against gastrointestinal nematodiasis in goats.

    PubMed

    Kumbhakar, N K; Sanyal, P K; Rawte, D; Kumar, D; Kerketta, A E; Pal, S

    2016-09-01

    To test the hypothesis that modulation of hepatic microsomal sulphoxidation and sulphonation by the cytochrome P450 inhibitor piperonyl butoxide could increase bioavailability of albendazole, the present study was undertaken to understand the pharmacokinetics of albendazole in goats at a dose of 7.5 mg kg- 1 body weight with and without co-administration with piperonyl butoxide at 63.0 mg kg- 1 body weight. Plasma albendazole sulphoxide metabolite, the anthelmintically active moiety, reached its maximum concentration of 0.322 ± 0.045 μg ml- 1 and 0.384 ± 0.013 μg ml- 1 at 18 h and 24 h after administration of albendazole alone and co-administration of albendazole with piperonyl butoxide, respectively. Analysis of the data revealed statistically increased albendazole sulphoxide levels at 24 (P 0.05) in values of maximum concentration (normal and calculated) could be observed between groups of goats. However, values of time to reach the concentration maximum (normal and calculated), area under the concentration-time curve (0-∞ and calculated), minimum residence time, distribution half-life, elimination half-life and total area under the first movement of plasma drug concentration-time curve were significantly higher (P <  0.05) in plasma levels of albendazole sulphoxide in goats following single oral co-administration of albendazole with piperonyl butoxide. The faecal egg count reduction and lower 95% confidence limit for the group treated with albendazole alone were 97 and 68%, while for co-administration of albendazole and piperonyl butoxide the values were 99 and 97%, respectively. The ED50 for egg hatch was 0.196, indicating suspected resistance to benzimidazole anthelmintics. The drug combination proved efficacious against an albendazole-resistant nematode parasite population in goats. PMID:26566193

  4. Identification of Methionine Sulfoxide Diastereomers in Immunoglobulin Gamma Antibodies Using Methionine Sulfoxide Reductase enzymes

    SciTech Connect

    Khor, Hui K.; Jacoby, Michael E.; Squier, Thomas C.; Chu, Grace C.; Chelius, Dirk

    2010-06-01

    During prolonged periods of storage methionines in antibodies and other proteins are known to become oxidized to form methionine sulfoxides and sulfones. While these post-translational modifications are commonly identified by peptide mapping, it is currently problematic to identify the relative abundances of the S- and R-diastereomers of methionine sulfoxide (Met(O)) due to their identical polarities and masses. Accordingly, we have developed a separation methodology for the rapid and quantitative determination of the relative abundances of Met(O) diastereomers. Identification of these diastereomers takes advantage of the complementary stereospecificities of methionine sulfoxide reductase (Msr) enzymes MsrA and MsrB, which respectively promote the selective reduction of S- and R-diastereomers of Met(O). In addition, an MsrBA fusion protein that contained both Msr enzyme activities permitted the quantitative reduction of all Met(O). Using these Msr enzymes in combination with peptide mapping we are able to detect and differentiate Met-diastereomers in a monoclonal IgG2 and IgG1 antibody. We also monitored the formation of sulfones and studied the rate of oxidation in the different Met residues in our IgG2 antibody. The reported ability to separate and identify diastereomers of Met(O) permits a more complete characterization of Met oxidation products. All the affected Met residues (M251, M427, M396) in this study are conserved in human IgG sequences and therefore offer predictive potential in characterizing oxidative modification.

  5. Ivermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection

    PubMed Central

    Henriquez-Camacho, Cesar; Gotuzzo, Eduardo; Echevarria, Juan; White, A Clinton; Terashima, Angelica; Samalvides, Frine; Pérez-Molina, José A; Plana, Maria N

    2016-01-01

    Background Strongyloidiasis is a gut infection with Strongyloides stercoralis which is common world wide. Chronic infection usually causes a skin rash, vomiting, diarrhoea or constipation, and respiratory problems, and it can be fatal in people with immune deficiency. It may be treated with ivermectin or albendazole or thiabendazole. Objectives To assess the effects of ivermectin versus benzimidazoles (albendazole and thiabendazole) for treating chronic strongyloides infection. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register (24 August 2015); the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE (January 1966 to August 2015); EMBASE (January 1980 to August 2015); LILACS (August 2015); and reference lists of articles. We also searched the metaRegister of Controlled Trials (mRCT) using 'strongyloid*' as a search term, reference lists, and conference abstracts. Selection criteria Randomized controlled trials of ivermectin versus albendazole or thiabendazole for treating chronic strongyloides infection. Data collection and analysis Two review authors independently extracted data and assessed risk of bias in the included trials. We used risk ratios (RRs) with 95% confidence intervals (CIs) and fixed- or random-effects models. We pooled adverse event data if the trials were sufficiently similar in their adverse event definitions. Main results We included seven trials, enrolling 1147 participants, conducted between 1994 and 2011 in different locations (Africa, Southeast Asia, America and Europe). In trials comparing ivermectin with albendazole, parasitological cure was higher with ivermectin (RR 1.79, 95% CI 1.55 to 2.08; 478 participants, four trials, moderate quality evidence). There were no statistically significant differences in adverse events (RR 0.80, 95% CI 0.59 to 1.09; 518 participants, four trials, low quality evidence). In trials comparing ivermectin with thiabendazole

  6. The use of albendazole for the treatment of trematodiasis in two tree shrews (Tupala glis)

    USGS Publications Warehouse

    Beehler, B.A.; Tuggle, B.N.

    1983-01-01

    Albendazole is a broad-spectrum anthelmintic of the benzimidazole group which has been tested in several rodents and domestic animals. Albendazole has been used effectively to treat trematodes in sheep, cattle, dogs, and cats. The use of this anthelmintic in exotic small mammals has not been reported to the authors' knowledge.

  7. Dimethyl sulfoxide: history, chemistry, and clinical utility in dermatology.

    PubMed

    Capriotti, Kara; Capriotti, Joseph A

    2012-09-01

    Dimethyl sulfoxide is a colorless liquid derived as a by-product from wood pulp in the production of paper. This colorless liquid found immediate application as a polar, aprotic solvent miscible with water and able to dissolve an enormous catalog of polar and nonpolar small molecules. It is presently scarcely used in dermatology, but given its useful properties as a penetration-enhancing solvent excipient and active anti-inflammatory pharmaceutical agent, dimethyl sulfoxide has the potential to be used in a much broader capacity. The authors review the history, chemistry, and clinical utility of dimethyl sulfoxide as it pertains to dermatology.

  8. Enantioselective Syntheses of Both Enantiomers of Noranabasamine

    PubMed Central

    Miao, Lei; DiMaggio, Stassi C.; Shu, Hong

    2009-01-01

    Both the R and S enantiomers of the amphibian alkaloid noranabasamine were prepared in > 30% overall yield with 80% ee and 86% ee, respectively. An enantioselective iridium catalyzed N-heterocyclization reaction with either (R)- or (S)-1-phenylethylamine and 1-(5-methoxypyridin-3-yl)-1,5-pentanediol was employed to generate the 2-(pyridin-3-yl)-piperidine ring system in 69–72% yield. PMID:19320505

  9. Nondipole Photoemission from Chiral Enantiomers of Camphor

    NASA Astrophysics Data System (ADS)

    Bowen, K. P.; Stolte, W. C.; Young, J. A.; Demchenko, I. N.; Guillemin, R.; Hemmers, O.; Piancastelli, M. N.; Lindle, D. W.

    2010-03-01

    K-shell photoemission from the carbonyl carbon in the chiral molecule camphor has been studied in the region just above the core-shell ionization threshold. Differences between angular distributions of emitted photoelectrons from the two enantiomers are attributed to the influence of chirality combined with nondipole effects in the photoemission process, despite the fact the measurements were taken using linearly polarized x-rays. The results suggest the possibility of a new form of linear dichroism.

  10. Bioactivity, toxicity and dissipation of hexaconazole enantiomers.

    PubMed

    Han, Jiajun; Jiang, Jiazhen; Su, Hang; Sun, Mingjing; Wang, Peng; Liu, Donghui; Zhou, Zhiqiang

    2013-11-01

    In this study, the bioactivity, acute toxicity and dissipation in vegetables of the individual enantiomers of the fungicide hexaconazole had been investigated. The optical pure single enantiomers were prepared and the bioactivity of (+)-, (-)- and rac-hexaconazole was tested using four target fungi including Colletotrichum gloeosporioides Penz, Alternaria solani, Alternaria mali Roberts and Monilinia fructicola. The results showed (-)-hexaconazole was always more active than (+)-hexaconazole with the fungicidal activity 11–13-fold higher to A. solani, A. mali Roberts and Monilinia fructicola, and 1.26-fold higher to C. gloeosporioides Penz. (-)-Hexaconazole also showed 1.3-fold higher acute toxicity to aquatic species Daphnia magna based on the 48 h EC50 values. There was obvious enantioselectivity in the dissipation in tomato with (-)-hexaconazole degraded faster resulting an enrichment of (+)-form, and the half-lives of (-)-hexaconazole and (+)-hexaconazole in tomato were 2.96 d and 3.38 d respectively, while it was not enantioselective in green pepper, in which the both enantiomers had the half-lives about 4.36 d. The findings are helpful for better environmental and ecological risk assessment of hexaconazole on an enantiomeric level. PMID:24206830

  11. Development of chiral sulfoxide ligands for asymmetric catalysis.

    PubMed

    Trost, Barry M; Rao, Meera

    2015-04-20

    Nitrogen-, phosphorus-, and oxygen-based ligands with chiral backbones have been the historic workhorses of asymmetric transition-metal-catalyzed reactions. On the contrary, sulfoxides containing chirality at the sulfur atom have mainly been used as chiral auxiliaries for diastereoselective reactions. Despite several distinct advantages over traditional ligand scaffolds, such as the proximity of the chiral information to the metal center and the ability to switch between S and O coordination, these compounds have only recently emerged as a versatile class of chiral ligands. In this Review, we detail the history of the development of chiral sulfoxide ligands for asymmetric catalysis. We also provide brief descriptions of metal-sulfoxide bonding and strategies for the synthesis of enantiopure sulfoxides. Finally, insights into the future development of this underutilized ligand class are discussed.

  12. Acyclic Cucurbit[n]uril-Type Molecular Container Enables Systemic Delivery of Effective Doses of Albendazole for Treatment of SK-OV-3 Xenograft Tumors.

    PubMed

    Hettiarachchi, Gaya; Samanta, Soumen K; Falcinelli, Shane; Zhang, Ben; Moncelet, Damien; Isaacs, Lyle; Briken, Volker

    2016-03-01

    Approximately, 40-70% of active pharmaceutical ingredients (API) are severely limited by their extremely poor aqueous solubility, and consequently, there is a high demand for excipients that can be used to formulate clinically relevant doses of these drug candidates. Here, proof-of-concept studies demonstrate the potential of our recently discovered acyclic cucurbit[n]uril-type molecular container Motor1 (M1) as a solubilizing agent for insoluble drugs. M1 did not induce significant rates of mutations in various Salmonella typhimurium test strains during the Ames test, suggesting low genotoxicity. M1 also has low risk of causing cardiac toxicity in humans since it did not inhibit the human Ether-à-go-go-Related Gene channel as tested on transfected CHO cell lines via patch clamp analysis. Albendazole (ABZ) is a widely used antihelminthic agent but that has also shown promising efficacy against cancerous cells in vitro. However, due to its low aqueous solubility (2.7 μM) and poor pharmacokinetics, ABZ is clinically limited as an anticancer agent. Here we investigated the potential of M1 as a solubilizing excipient for ABZ formulation. A pharmacokinetic study indicated that ABZ escapes the peritoneal cavity resulting in 78% absolute bioavailability, while its active intermediate metabolite, albendazole sulfoxide, achieved 43% absolute bioavailability. The daily dosing of 681 mg/kg M1 complexed with 3.2 mg/kg of ABZ for 14 days did not result in significant weight loss or pathology in Swiss Webster mice. In vivo efficacy studies using this M1·ABZ inclusion complex showed significant decreases in tumor growth rates and increases in survival of mice bearing SK-OV-3 xenograft tumors. In conclusion, we provide substantial new evidence demonstrating that M1 is a safe and efficient excipient that enables in vivo parenteral delivery of poorly water-soluble APIs.

  13. Acyclic Cucurbit[n]uril-Type Molecular Container Enables Systemic Delivery of Effective Doses of Albendazole for Treatment of SK-OV-3 Xenograft Tumors.

    PubMed

    Hettiarachchi, Gaya; Samanta, Soumen K; Falcinelli, Shane; Zhang, Ben; Moncelet, Damien; Isaacs, Lyle; Briken, Volker

    2016-03-01

    Approximately, 40-70% of active pharmaceutical ingredients (API) are severely limited by their extremely poor aqueous solubility, and consequently, there is a high demand for excipients that can be used to formulate clinically relevant doses of these drug candidates. Here, proof-of-concept studies demonstrate the potential of our recently discovered acyclic cucurbit[n]uril-type molecular container Motor1 (M1) as a solubilizing agent for insoluble drugs. M1 did not induce significant rates of mutations in various Salmonella typhimurium test strains during the Ames test, suggesting low genotoxicity. M1 also has low risk of causing cardiac toxicity in humans since it did not inhibit the human Ether-à-go-go-Related Gene channel as tested on transfected CHO cell lines via patch clamp analysis. Albendazole (ABZ) is a widely used antihelminthic agent but that has also shown promising efficacy against cancerous cells in vitro. However, due to its low aqueous solubility (2.7 μM) and poor pharmacokinetics, ABZ is clinically limited as an anticancer agent. Here we investigated the potential of M1 as a solubilizing excipient for ABZ formulation. A pharmacokinetic study indicated that ABZ escapes the peritoneal cavity resulting in 78% absolute bioavailability, while its active intermediate metabolite, albendazole sulfoxide, achieved 43% absolute bioavailability. The daily dosing of 681 mg/kg M1 complexed with 3.2 mg/kg of ABZ for 14 days did not result in significant weight loss or pathology in Swiss Webster mice. In vivo efficacy studies using this M1·ABZ inclusion complex showed significant decreases in tumor growth rates and increases in survival of mice bearing SK-OV-3 xenograft tumors. In conclusion, we provide substantial new evidence demonstrating that M1 is a safe and efficient excipient that enables in vivo parenteral delivery of poorly water-soluble APIs. PMID:26756920

  14. Glass transition dynamics of enantiomer (+)-ibuprofen

    NASA Astrophysics Data System (ADS)

    Kim, Tae Hyun; Ko, Jae-Hyeon; Takayama, Haruki; Shibata, Tomohiko; Kojima, Seiji

    2013-02-01

    The acoustic properties and dynamic heat capacity of enantiomer (+)-Ibuprofen were investigated in a wide temperature including glassy and supercooled liquid and equilibrium liquid states. The Brillouin frequency shift and the full width at half maximum of the longitudinal acoustic waves of glassy ibuprofen exhibited clear changes at the glass transition temperature of 223 K. The fragility of (+)-Ibuprofen was determined to be 68 using the temperature dependence of relaxation time obtained from the imaginary part of the complex dynamic heat capacity. The sound velocity, the attenuation coefficient, and the thermal expansion coefficient were determined in the liquid (+)-Ibuprofen based on the measurements of the refractive index.

  15. Residue depletion of albendazole and its metabolites in aquacultured yellow perch (Perca flavescens).

    PubMed

    Yu, D; Evans, E R; Hasbrouck, N; Reimschuessel, R; Shaikh, B

    2012-12-01

    Metabolism and residue depletion studies are conducted to determine the marker residue (MR) of a drug in a target tissue of food animals. The MR is used to monitor potential unauthorized use of drugs. The current work is a continuation of our efforts to study metabolism and depletion profiles of albendazole in multiple finfish species to determine a common MR. The results of this study suggest that albendazole sulfone metabolite could potentially serve as MR for albendazole in yellow perch muscle, similar to channel catfish and hybrid striped bass as reported previously by us. PMID:22150530

  16. Comparative Plasma Exposure of Albendazole after Administration of Rapidly Disintegrating Tablets in Dogs

    PubMed Central

    Castro, Silvina G.; Dib, Alicia; Suarez, Gonzalo; Allemandi, Daniel; Lanusse, Carlos; Sanchez Bruni, Sergio; Palma, Santiago D.

    2013-01-01

    The main objectives of this study were (a) to evaluate the in vitro performance of the rapid disintegration tablets as a way to improve the solid dispersions and (b) to study the in vivo pharmacokinetics of the albendazole modified formulation in dogs. Rapid disintegration of tablets seems to be a key factor for efficiency of solid dispersions with regard to improvement of the albendazole bioavailability. The in vivo assays performed on dogs showed a marked increase in drug plasma exposure when albendazole was given in solid dispersions incorporated into rapid disintegration tablets compared with conventional solid dosage form. PMID:24063016

  17. Albendazole therapy of hydatid disease: 2-year follow-up of 40 cases.

    PubMed

    el-Mufti, M; Kamag, A; Ibrahim, H; Taktuk, S; Swaisi, I; Zaidan, A; Sameen, A; Shimbish, F; Bouzghaiba, W; Haasi, S

    1993-06-01

    Forty patients with 63 Echinococcus granulosus cysts affecting different sites were treated with albendazole and have been followed up for at least 24 months from completion of therapy. Twenty-one patients (53%) with 37 cysts (59%) showed evidence of healing. The criteria and pattern of healing are outlined. The most serious complication of albendazole therapy was hepatoxic jaundice, which occurred in 5% of patients. Recurrence during the observation period was encountered in 9.5% of patients with a positive response. It is suggested that patients suffering from uncomplicated hydatid disease should be given the benefit of a trial course of albendazole therapy, before surgery is undertaken.

  18. The Methionine Sulfoxide Reduction System: Selenium Utilization and Methionine Sulfoxide Reductase Enzymes and Their Functions

    PubMed Central

    2013-01-01

    Abstract Significance: Selenium is utilized in the methionine sulfoxide reduction system that occurs in most organisms. Methionine sulfoxide reductases (Msrs), MsrA and MsrB, are the enzymes responsible for this system. Msrs repair oxidatively damaged proteins, protect against oxidative stress, and regulate protein function, and have also been implicated in the aging process. Selenoprotein forms of Msrs containing selenocysteine (Sec) at the catalytic site are found in bacteria, algae, and animals. Recent Advances: A selenoprotein MsrB1 knockout mouse has been developed. Significant progress in the biochemistry of Msrs has been made, which includes findings of a novel reducing system for Msrs and of an interesting reason for the use of Sec in the Msr system. The effects of mammalian MsrBs, including selenoprotein MsrB1 on fruit fly aging, have been investigated. Furthermore, it is evident that Msrs are involved in methionine metabolism and regulation of the trans-sulfuration pathway. Critical Issues: This article presents recent progress in the Msr field while focusing on the physiological roles of mammalian Msrs, functions of selenoprotein forms of Msrs, and their biochemistry. Future Directions: A deeper understanding of the roles of Msrs in redox signaling, the aging process, and metabolism will be achieved. The identity of selenoproteome of Msrs will be sought along with characterization of the identified selenoprotein forms. Exploring new cellular targets and new functions of Msrs is also warranted. Antioxid. Redox Signal. 19, 958–969. PMID:23198996

  19. Enantioselective toxic effects of cyproconazole enantiomers against Chlorella pyrenoidosa.

    PubMed

    Zhang, Wenjun; Cheng, Cheng; Chen, Li; Di, Shanshan; Liu, Chunxiao; Diao, Jinling; Zhou, Zhiqiang

    2016-09-01

    Enantioselectivity in ecotoxicity, digestion and uptake of chiral pesticide cyproconazole to Chlorella pyrenoidosa was studied. The 96h-EC50 values of rac- and the four enantiomers were 9.005, 6.616, 8.311, 4.290 and 9.410 mg/L, respectively. At the concentrations of 8 mg/L and 14 mg/L, the contents of pigments exposed in rac-, enantiomer-2 and 4 were higher than that exposed in enantiomer-1 and 3. The superoxide dismutase (SOD) and catalase (CAT) activity of algae exposed to enantiomer-1 and 3 was higher than that exposed to the rac-, enantiomer-2 and 4 at three levels. In addition, the malondialdehyde (MDA) concentrations in algae disposed with enantiomer-1 and 3 were increased remarkably at three levels. For the digestion experiment, the half-lives of four enantiomers in algae suspension were 28.06, 19.10, 21.13, 15.17 days, respectively. During the uptake experiment, the order of the concentrations of cyproconazole in algae cells was enantiomer-4, 2, 3 and 1. Based on these data, we concluded that ecotoxicity, digestion and uptake of chiral pesticide cyproconazole to C. pyrenoidosa were enantioselective, and such enantiomeric differences must be taken into consideration when assessing the risk of cyproconazole to environment. PMID:27268794

  20. Differentiation of enantiomers by capillary electrophoresis.

    PubMed

    Scriba, Gerhard K E

    2013-01-01

    Capillary electrophoresis (CE) has matured to one of the major liquid phase enantiodifferentiation techniques since the first report in 1985. This can be primarily attributed to the flexibility as well as the various modes available including electrokinetic chromatography (EKC), micellar electrokinetic chromatography (MEKC), and microemulsion electrokinetic chromatography (MEEKC). In contrast to chromatographic techniques, the chiral selector is mobile in the background electrolyte. Furthermore, a large variety of chiral selectors are available that can be easily combined in the same separation system. In addition, the migration order of the enantiomers can be adjusted by a number of approaches. In CE enantiodifferentiations the separation principle is comparable to chromatography while the principle of the movement of the analytes in the capillary is based on electrophoretic phenomena. The present chapter will focus on mechanistic aspects of CE enantioseparations including enantiomer migration order and the current understanding of selector-selectand structures. Selected examples of the basic enantioseparation modes EKC, MEKC, and MEEKC will be discussed. PMID:23666080

  1. Efficacy of intraruminal albendazole boluses against Dicrocoelium dendriticum in sheep.

    PubMed

    Corba, J; Krupicer, I

    1992-01-01

    The anthelmintic potential of albendazole (ABZ) in intraruminal boluses (Proftril-Captec) was investigated in sheep harbouring naturally acquired Dicrocoelium infection. The anthelmintic efficacy was assessed by coprological testing during the autumn pasture and comparison of worm counts in 22 necropsied animals (11 treated and 11 untreated) at the end of the experiment. The mean faecal egg count (EPG) in treated animals dropped significantly during week 2, and between the 4th and the 12th week the faecal samples were almost negative. The health status of treated animals improved significantly during the first 2 weeks. Helminthological dissection of livers and small intestines revealed 91.8% efficacy, but a small number of live adult flukes were found in all treated animals.

  2. The role of empirical albendazole treatment in idiopathic hypereosinophilia – a case series

    PubMed Central

    Vaisben, Eleonora; Brand, Ronen; Kadakh, Anas; Nassar, Faris

    2015-01-01

    Hypereosinophilia is usually defined as a blood eosinophil count >1500/μL. A broad variety of conditions are associated with hypereosinophilia. The present report describes three cases of hypereosinophilia, in which a thorough history, physical examination, laboratory and imaging investigations were unable to detect any abnormalities. Albendazole was empirically administered in all three cases, with complete normalization of eosinophil counts thereafter. Empirical treatment with albendazole for patients presenting with hypereosinophilia should be strongly considered. PMID:26744590

  3. Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization.

    PubMed

    Trost, Barry M; Ryan, Michael C; Rao, Meera

    2016-01-01

    A full account of our efforts toward an asymmetric redox bicycloisomerization reaction is presented in this article. Cyclopentadienylruthenium (CpRu) complexes containing tethered chiral sulfoxides were synthesized via an oxidative [3 + 2] cycloaddition reaction between an alkyne and an allylruthenium complex. Sulfoxide complex 1 containing a p-anisole moiety on its sulfoxide proved to be the most efficient and selective catalyst for the asymmetric redox bicycloisomerization of 1,6- and 1,7-enynes. This complex was used to synthesize a broad array of [3.1.0] and [4.1.0] bicycles. Sulfonamide- and phosphoramidate-containing products could be deprotected under reducing conditions. Catalysis performed with enantiomerically enriched propargyl alcohols revealed a matched/mismatched effect that was strongly dependent on the nature of the solvent. PMID:27559366

  4. Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

    PubMed Central

    Ryan, Michael C; Rao, Meera

    2016-01-01

    Summary A full account of our efforts toward an asymmetric redox bicycloisomerization reaction is presented in this article. Cyclopentadienylruthenium (CpRu) complexes containing tethered chiral sulfoxides were synthesized via an oxidative [3 + 2] cycloaddition reaction between an alkyne and an allylruthenium complex. Sulfoxide complex 1 containing a p-anisole moiety on its sulfoxide proved to be the most efficient and selective catalyst for the asymmetric redox bicycloisomerization of 1,6- and 1,7-enynes. This complex was used to synthesize a broad array of [3.1.0] and [4.1.0] bicycles. Sulfonamide- and phosphoramidate-containing products could be deprotected under reducing conditions. Catalysis performed with enantiomerically enriched propargyl alcohols revealed a matched/mismatched effect that was strongly dependent on the nature of the solvent. PMID:27559366

  5. Excited state dynamics and isomerization in ruthenium sulfoxide complexes.

    PubMed

    King, Albert W; Wang, Lei; Rack, Jeffrey J

    2015-04-21

    Molecular photochromic compounds are those that interconvert between two isomeric forms with light. The two isomeric forms display distinct electronic and molecular structures and must not be in equilibrium with one another. These light-activated molecular switch compounds have found wide application in areas of study ranging from chemical biology to materials science, where conversion from one isomeric form to another by light prompts a response in the environment (e.g., protein or polymeric material). Certain ruthenium and osmium polypyridine sulfoxide complexes are photochromic. The mode of action is a phototriggered isomerization of the sulfoxide from S- to O-bonded. The change in ligation drastically alters both the spectroscopic and electrochemical properties of the metal complex. Our laboratory has pioneered the preparation and study of these complexes. In particular, we have applied femtosecond pump-probe spectroscopy to reveal excited state details of the isomerization mechanism. The data from numerous complexes allowed us to predict that the isomerization was nonadiabatic in nature, defined as occurring from a S-bonded triplet excited state (primarily metal-to-ligand charge transfer in character) to an O-bonded singlet ground state potential energy surface. This prediction was corroborated by high-level density functional theory calculations. An intriguing aspect of this reactivity is the coupling of nuclear motion to the electronic wave function and how this coupling affects motions productive for isomerization. In an effort to learn more about this coupling, we designed a project to examine phototriggered isomerization in bis-sulfoxide complexes. The goal of these studies was to determine whether certain complexes could be designed in which a single photon excitation event would prompt two sulfoxide isomerizations. We employed chelating sulfoxides in this study and found that both the nature of the chelate ring and the R group on the sulfoxide affect

  6. Spin crossover properties of enantiomers, co-enantiomers, racemates, and co-racemates.

    PubMed

    Qin, Long-Fang; Pang, Chun-Yan; Han, Wang-Kang; Zhang, Feng-Li; Tian, Lei; Gu, Zhi-Guo; Ren, Xuehong; Li, Zaijun

    2016-04-25

    Through multi-component self-assembly of chiral phenylethylamine, 1-alkyl-2-imidazolecarboxaldehyde and iron(ii) ions, two couples of enantiomeric iron(ii) complexes , , and with the formula of fac-Λ or Δ-[Fe(L)3](2+)(L = R or S-1-phenyl-N-(1-alkyl-1H-imidazol-2-ylmethylene)ethanamine) have been designed and synthesized as building blocks. Further binary cocrystallization of the prefabricated enantiomers enabled us to construct spin crossover co-enantiomers and , racemates and , and co-racemate . Compared with in a high spin state and with spin crossover at 291 K, the co-enantiomers exhibited gradual spin crossover at a higher temperature of 301 K, and the racemic alloys showed hysteresis loops induced by desolvation above room temperature. It was demonstrated that molecular chirality could be used effectively for stereochemical engineering of spin crossover materials. In addition, crystal packing, intramolecular π-π stacking, intermolecular C-Hπ interactions and solvent effects were elucidated to be responsible for the distinct spin crossover properties. This collective structural and magnetic study not only enriched the spin crossover library, but also provided a full comparison of optically pure, homochiral, and racemic materials with similar molecular structures. PMID:27021212

  7. The cytotoxicity study of praziquantel enantiomers.

    PubMed

    Sun, Qian; Mao, Ruifeng; Wang, Dongling; Hu, Changyan; Zheng, Yang; Sun, Dequn

    2016-01-01

    Praziquantel (PZQ) is prescribed as a racemic mixture (racemic-PZQ, rac-PZQ), which is composed of (R)-PZQ and (S)-PZQ. In this work, the cytotoxicity of rac-PZQ and its two enantiomers (R)-PZQ and (S)-PZQ on eight cell lines (L-02, HepG2, prf-plc-5, SH-SY5Y, HUVEC, A549, HCT-15, Raw264.7) was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphe-nyltetrazolium bromide and lactate dehydrogenase assays. The morphology of apoptotic cells was studied by fluorescence microscope using Hoechst 33342 staining, and the cytotoxicity of the compounds was also tested by lactate dehydrogenase assay. Results revealed that (R)-PZQ had negligible cytotoxicity against L-02, SH-SY5Y, HUVEC, A549, HCT-15, and Raw264.7 cells but selectively inhibited tumor cell lines (prf-plc-5 and HepG2). However, in contrast to (R)-PZQ, the (S)-isomer showed higher cytotoxicity against L-02 cells and lower inhibition on prf-plc-5 and HepG2 cells. Besides, (R)-PZQ showed lower cytotoxicity on SH-SY5Y cells than (S)-PZQ. Meanwhile, (R)-PZQ at <80 μM concentration could promote proliferation of macrophage cells (Raw264.7). Our research revealed that (R)-PZQ has lower cytotoxicity than (S)-PZQ and has similar cytotoxicity with rac-PZQ. (S)-PZQ is the principal enantiomer to cause side effects on human definitive hosts. These findings gave the reasonable reasons for World Health Organization to produce (R)-PZQ as a replacement for rac-PZQ for the treatment of schistosomiasis. PMID:27445457

  8. Possible selective adsorption of enantiomers by Na-montmorillonite

    NASA Technical Reports Server (NTRS)

    Friebele, E.; Shimoyama, A.; Ponnamperuma, C.

    1981-01-01

    Racemic amino acids including (D,L) alpha-alamine, (D,L) alpha-aminobutyric acid, (D,L) valine, and (D,L) norvaline were incubated with Na-montmorillonite at 100% CEC at three hydrogen ion concentrations, and amino acid adsorption was determined by ion exchange chromatography. Enantiomers were analyzed by gas chromatography. Differences in the quantities of D and L enantiomers in any of the fractions was no larger than a few percent. Although a large difference in the adsorption of the amino acid enantiomers was not observed, the analysis may indicate a small preferential adsorption (0.5-2%) of L-amino acids by Na-montmorillonite.

  9. Demonstration of Enantiomer Specificity of Proteins and Drugs

    ERIC Educational Resources Information Center

    Anderson, Gretchen L.; Page, Shallee T.

    2004-01-01

    Classroom demonstrations and activities are used to illustrate the properties of enantiomer. During this activity, in a relatively short time students develop a working knowledge of the importance of stereochemistry in biochemistry and its effect on drug design and metabolism.

  10. Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: a double-blind, randomised controlled trial

    PubMed Central

    Garcia, Hector H; Gonzales, Isidro; Lescano, Andres G; Bustos, Javier A; Zimic, Mirko; Escalante, Diego; Saavedra, Herbert; Gavidia, Martin; Rodriguez, Lourdes; Najar, Enrique; Umeres, Hugo; Pretell, E Javier

    2014-01-01

    Summary Background Neurocysticercosis causes a substantial burden of seizure disorders worldwide. Treatment with either praziquantel or albendazole has suboptimum efficacy. We aimed to establish whether combination of these drugs would increase cysticidal efficacy and whether complete cyst resolution results in fewer seizures. We added an increased dose albendazole group to establish a potential effect of increased albendazole concentrations. Methods In this double-blind, placebo-controlled, phase 3 trial, patients with viable intraparenchymal neurocysticercosis were randomly assigned to receive 10 days of combined albendazole (15 mg/kg per day) plus praziquantel (50 mg/kg per day), standard albendazole (15 mg/kg per day), or increased dose albendazole (22·5 mg/kg per day). Randomisation was done with a computer generated schedule balanced within four strata based on number of cysts and concomitant antiepileptic drug. Patients and investigators were masked to group assignment. The primary outcome was complete cyst resolution on 6-month MRI. Enrolment was stopped after interim analysis because of parasiticidal superiority of one treatment group. Analysis excluded patients lost to follow-up before the 6-month MRI. This trial is registered with ClinicalTrials.gov, number NCT00441285. Findings Between March 3, 2010 and Nov 14, 2011, 124 patients were randomly assigned to study groups (41 to receive combined albendazole plus praziquantel [39 analysed], 43 standard albendazole [41 analysed], and 40 increased albendazole [38 analysed]). 25 (64%) of 39 patients in the combined treatment group had complete resolution of brain cysts compared with 15 (37%) of 41 patients in the standard albendazole group (rate ratio [RR] 1·75, 95% CI 1·10–2·79, p=0·014). 20 (53%) of 38 patients in the increased albendazole group had complete cyst resolution at 6-month MRI compared with 15 (37%) of 41 patients in the standard albendazole group (RR 1·44, 95% CI 0·87–2·38, p=0·151

  11. Synthesis, characterization, and metabolism studies of fluspidine enantiomers.

    PubMed

    Holl, Katharina; Falck, Evamaria; Köhler, Jens; Schepmann, Dirk; Humpf, Hans-Ulrich; Brust, Peter; Wünsch, Bernhard

    2013-12-01

    The enantiomers of the potent σ1 ligand fluspidine (1) were prepared by using chiral preparative HPLC. Synthesis of racemic tosylate 2 and subsequent separation of enantiomers yielded (R)-2 and (S)-2 in excellent enantiomeric purities. The fluspidine enantiomers (R)-1 and (S)-1 were synthesized from (R)-2 and (S)-2 by nucleophilic substitution with tetra-n-butylammonium fluoride, affording (R)-1 with 99.6 % ee and (S)-1 with 96.4 % ee. Tosylates (R)-2 and (S)-2 can also serve as precursors for the radiosynthesis of enantiomerically pure radiotracers [(18) F](R)-1 and [(18) F](S)-1. The absolute configuration of the pure enantiomers was elucidated by comparison of their CD spectra with a calculated CD spectrum of a simplified model compound. In receptor binding studies, both enantiomers displayed very high σ1 receptor affinity and selectivity against the σ2 receptor. (R)-Fluspidine ((R)-1) is the eutomer, with a Ki value of 0.57 nM and a eudysmic ratio of 4. Incubation of (R)-1 and (S)-1 with rat liver microsomes led to the identification of seven and eight metabolites, respectively. Although the S-configured enantiomer formed additional metabolite (S)-1-3, it is metabolically more stable than (R)-1.

  12. Investigating albendazole desmotropes by solid-state NMR spectroscopy.

    PubMed

    Chattah, Ana K; Zhang, Rongchun; Mroue, Kamal H; Pfund, Laura Y; Longhi, Marcela R; Ramamoorthy, Ayyalusamy; Garnero, Claudia

    2015-03-01

    Characterization of the molecular structure and physicochemical solid-state properties of the solid forms of pharmaceutical compounds is a key requirement for successful commercialization as potential active ingredients in drug products. These properties can ultimately have a critical effect on the solubility and bioavailability of the final drug product. Here, the desmotropy of Albendazole forms I and II was investigated at the atomic level. Ultrafast magic angle spinning (MAS) solid-state nuclear magnetic resonance (NMR) spectroscopy, together with powder X-ray diffraction, thermal analysis, and Fourier transform infrared spectroscopy, were performed on polycrystalline samples of the two solids in order to fully characterize and distinguish the two forms. High-resolution one-dimensional (1)H, (13)C, and (15)N together with two-dimensional (1)H/(1)H single quantum-single quantum, (1)H/(1)H single quantum-double quantum, and (1)H/(13)C chemical shift correlation solid-state NMR experiments under MAS conditions were extensively used to decipher the intramolecular and intermolecular hydrogen bonding interactions present in both solid forms. These experiments enabled the unequivocal identification of the tautomers of each desmotrope. Our results also revealed that both solid forms may be described as dimeric structures, with different intermolecular hydrogen bonds connecting the tautomers in each dimer. PMID:25584993

  13. Enantiomer-specific selection of amino acids.

    PubMed

    Ren, Xueying; Tellez, Luis A; de Araujo, Ivan E

    2013-12-01

    Dietary intake of L-amino acids impacts on several physiological functions, including the control of gastrointestinal motility, pancreatic secretion, and appetite. However, the biological mechanisms regulating behavioral predilections for certain amino acid types remain poorly understood. We tested the hypothesis that, in mice, the potency with which a given glucogenic amino acid increases glucose utilization reflects its rewarding properties. We have found that: (1) during long-, but not short-, term preference tests, L-alanine and L-serine were preferred over their D-enantiomer counterparts, while no such effect was observed for L-threonine vs. D-threonine; (2) these behavioral patterns were closely associated with the ability of L-amino acids to promote increases in respiratory exchange ratios such that those, and only those, L-amino acids able to promote increases in respiratory exchange ratios were preferred over their D-isomers; (3) these behavioral preferences were independent of gustatory influences, since taste-deficient Trpm5 knockout mice displayed ingestive responses very similar to those of their wild-type counterparts. We conclude that the ability to promote increases in respiratory exchange ratios enhances the reward value of nutritionally relevant amino acids and suggest a mechanistic link between substrate utilization and amino acid preferences.

  14. Safety of the Combined Use of Praziquantel and Albendazole in the Treatment of Human Hydatid Disease

    PubMed Central

    Alvela-Suárez, Lucía; Velasco-Tirado, Virginia; Belhassen-Garcia, Moncef; Novo-Veleiro, Ignacio; Pardo-Lledías, Javier; Romero-Alegría, Angela; Pérez del Villar, Luis; Valverde-Merino, María Paz; Cordero-Sánchez, Miguel

    2014-01-01

    There is still no well-established consensus about the clinical management of hydatidosis. Currently, surgery continues to be the first therapeutic option, although treatment with anti-parasitic drugs is indicated as an adjuvant to surgery to decrease the number of relapses and hydatid cyst size. When surgery is not possible, medical treatment is indicated. Traditionally, albendazole was used in monotherapy as the standard treatment. However, combined therapy with albendazole plus praziquantel appears to improve anti-parasitic effectiveness. To date, no safety studies focusing on such combined therapy have been published for the treatment of hydatidosis. In this work, we analyze the adverse effects seen in 57 patients diagnosed with hydatidosis who were treated with praziquantel plus albendazole combined therapy between 2006 and 2010. PMID:24615131

  15. An insect growth inhibitor--lufenuron--enhances albendazole activity against hydatid cyst.

    PubMed

    Breijo, Martín; Isnardi, Fernanda; Brauer, Mónica; Schenker, Rudolf; Ferrari, Mariana; Ferreira, Ana M

    2011-09-27

    The aim of this work was to evaluate the potential of lufenuron, a benzylphenylurea with ability to interfere with the formation of insect exoskeleton, as a therapeutic drug for larval echinococcosis (hydatid disease). For this purpose lufenuron, alone or in combination with albendazole, was administered to CD1 mice bearing Echinococcus granulosus hydatid cysts in the peritoneal cavity. Neither of the drugs alone was able to exert parasiticidal effects. However, in combination with albendazole, lufenuron reduced the growth of cysts (30-40% in cyst diameter respect to control, p<0.05). This effect was associated with ultrastructural alterations of the hydatid cyst wall and a reduction of the content of myo-inositol-hexakisphosphate, the major component of the electron dense granules of the laminated layer. Overall, this work provides evidence that lufenuron could represent a useful compound for the use in chemotherapy against larval echinococcosis, by enhancing albendazole parasiticidal activity. PMID:21592667

  16. Safety of the combined use of praziquantel and albendazole in the treatment of human hydatid disease.

    PubMed

    Alvela-Suárez, Lucía; Velasco-Tirado, Virginia; Belhassen-Garcia, Moncef; Novo-Veleiro, Ignacio; Pardo-Lledías, Javier; Romero-Alegría, Angela; Pérez del Villar, Luis; Valverde-Merino, María Paz; Cordero-Sánchez, Miguel

    2014-05-01

    There is still no well-established consensus about the clinical management of hydatidosis. Currently, surgery continues to be the first therapeutic option, although treatment with anti-parasitic drugs is indicated as an adjuvant to surgery to decrease the number of relapses and hydatid cyst size. When surgery is not possible, medical treatment is indicated. Traditionally, albendazole was used in monotherapy as the standard treatment. However, combined therapy with albendazole plus praziquantel appears to improve anti-parasitic effectiveness. To date, no safety studies focusing on such combined therapy have been published for the treatment of hydatidosis. In this work, we analyze the adverse effects seen in 57 patients diagnosed with hydatidosis who were treated with praziquantel plus albendazole combined therapy between 2006 and 2010. PMID:24615131

  17. [Ascariasis: comparison of the therapeutic efficacy between paico and albendazole in children from Huaraz].

    PubMed

    López De Guimaraes, D; Neyra Llanos, R S; Romero Acevedo, J H

    2001-01-01

    A therapeutical clinical trial was designed to study the effectiveness of Paico and Albendazole, for the treatment of ascariasis in a group of 60 children, between 3 and 14 years old, from a rural community in Huaraz. It was carried out between May and August, 2000. The sample was randomly divided into 30 cases for Paico and 30 for Albendazole, the criteria for entering the trial being a positive examination for Ascaris lumbricoides in feces. The treatment consisted in Paico juice: 1 ml/Kg for less than 10 Kg, and 2 ml/Kg in larger children, one dose before breakfast, for three consecutive days. The Albendazole was administered in a single dose of 400 mg in those over five years of age, and 200 mg in younger children. The effectiveness was evaluated qualitatively (the disappearance of the ascaris eggs from the feces) and quantitatively (decrease in the parasitic burden); in the stool examinations carried out in all cases on entering the study and 15 days after the treatment. All the stool samples were processed in the Referential Laboratory of the Regional Health Authority in Ancash. The qualitative effectiveness between Paico and Albendazole for the eradication of ascariasis was similar at 86.7%. The quantitative effectiveness was 59.5% for Paico and 58.3% for Albendazole. However, it was observed that, unlike Albedazole, Paico is 100% effective in the treatment of Hymenolepsis nana. Adverse effects were presented in 23.3% of the cases for both drugs. It is concluded that, although Paico and Albendazole have a similar effectiveness against Ascaris lumbricoides, Paico has the additional benefit of being effective against Hymenolepsis nana.

  18. [Ascariasis: comparison of the therapeutic efficacy between paico and albendazole in children from Huaraz].

    PubMed

    López De Guimaraes, D; Neyra Llanos, R S; Romero Acevedo, J H

    2001-01-01

    A therapeutical clinical trial was designed to study the effectiveness of Paico and Albendazole, for the treatment of ascariasis in a group of 60 children, between 3 and 14 years old, from a rural community in Huaraz. It was carried out between May and August, 2000. The sample was randomly divided into 30 cases for Paico and 30 for Albendazole, the criteria for entering the trial being a positive examination for Ascaris lumbricoides in feces. The treatment consisted in Paico juice: 1 ml/Kg for less than 10 Kg, and 2 ml/Kg in larger children, one dose before breakfast, for three consecutive days. The Albendazole was administered in a single dose of 400 mg in those over five years of age, and 200 mg in younger children. The effectiveness was evaluated qualitatively (the disappearance of the ascaris eggs from the feces) and quantitatively (decrease in the parasitic burden); in the stool examinations carried out in all cases on entering the study and 15 days after the treatment. All the stool samples were processed in the Referential Laboratory of the Regional Health Authority in Ancash. The qualitative effectiveness between Paico and Albendazole for the eradication of ascariasis was similar at 86.7%. The quantitative effectiveness was 59.5% for Paico and 58.3% for Albendazole. However, it was observed that, unlike Albedazole, Paico is 100% effective in the treatment of Hymenolepsis nana. Adverse effects were presented in 23.3% of the cases for both drugs. It is concluded that, although Paico and Albendazole have a similar effectiveness against Ascaris lumbricoides, Paico has the additional benefit of being effective against Hymenolepsis nana. PMID:11818981

  19. Monitoring methionine sulfoxide with stereospecific mechanism-based fluorescent sensors.

    PubMed

    Tarrago, Lionel; Péterfi, Zalán; Lee, Byung Cheon; Michel, Thomas; Gladyshev, Vadim N

    2015-05-01

    Methionine can be reversibly oxidized to methionine sulfoxide (MetO) under physiological and pathophysiological conditions, but its use as a redox marker suffers from the lack of tools to detect and quantify MetO within cells. In this work, we created a pair of complementary stereospecific genetically encoded mechanism-based ratiometric fluorescent sensors of MetO by inserting a circularly permuted yellow fluorescent protein between yeast methionine sulfoxide reductases and thioredoxins. The two sensors, respectively named MetSOx and MetROx for their ability to detect S and R forms of MetO, were used for targeted analysis of protein oxidation, regulation and repair as well as for monitoring MetO in bacterial and mammalian cells, analyzing compartment-specific changes in MetO and examining responses to physiological stimuli.

  20. Aryne 1,2,3-Trifunctionalization with Aryl Allyl Sulfoxides.

    PubMed

    Li, Yuanyuan; Qiu, Dachuan; Gu, Rongrong; Wang, Junli; Shi, Jiarong; Li, Yang

    2016-08-31

    An aryne 1,2,3-trisubstitution with aryl allyl sulfoxides is accomplished, featuring an incorporation of C-S, C-O, and C-C bonds on the consecutive positions of a benzene ring. The reaction condition is mild with broad substrate scope. Preliminary mechanistic study suggests a cascade formal [2 + 2] reaction of aryne with S═O bond, an allyl S → O migration, and a Claisen rearrangement. PMID:27527334

  1. Odour character differences for enantiomers correlate with molecular flexibility

    PubMed Central

    Brookes, Jennifer C; Horsfield, A.P; Stoneham, A.M

    2008-01-01

    The olfactory system sensitively discerns scents from many small molecules as the brain analyses signals from nasal receptors. These receptors are selective to some degree, though the mechanism for selectivity is still controversial. Enantiomers, chiral pairs of left- and right-handed structures, are an important class of molecules in assessing proposed mechanisms. We show that there is a correlation between molecular (structural) flexibility and whether or not the left- and right-handed enantiomers smell the same. In particular, for the fairly extensive class of enantiomers with six-membered ring flexibility, enantiomers do not smell the same. There are, of course, significant experimental uncertainties, which we discuss here. We discuss models of receptor selectivity, both those based on shape and those where discrimination is based on other factors, such as electron affinity, proton affinity or vibration frequencies. The differences in scent of these enantiomers appear to be consistent with simple generalizations of a ‘swipe card’ model in which, while the shape must be good enough, critical information for actuation is a separate factor. PMID:18595834

  2. Albendazole and its metabolites in the breast milk of lactating women following a single oral dose of albendazole

    PubMed Central

    Abdel-tawab, Ahmed M; Bradley, Mark; Ghazaly, Essam A; Horton, John; El-Setouhy, Maged

    2009-01-01

    AIMS Albendazole (ABZ) is used in several anthelminthic drug programmws. ABZ side-effects are generally mild, but ABZ-induced pancytopenia may be serious. In filariasis programmes, it may be necessary to administer ABZ to breastfeeding women. Few data are available on safety of ABZ for breastfed infants. In addition, the pharmacokinetics of ABZ and its metabolites in human milk is insufficiently investigated. The aim was to study pharmacokinetics of ABZ and its metabolites [ABZ sulphoxide (ABSX) and ABZ sulphone] in the breast milk lactating women after one single oral dose of ABZ. METHODS Thirty-three lactating women (age 18–40 years) participated in the study. They received a single oral 400-mg dose of ABZ. Five milk samples were taken at 0, 6, 12, 24 and 36 h. One serum sample was taken after 6 h. Samples were analysed using high-performance liquid chromatography and pharmacokinetic analysis was performed. RESULTS ABZ was detectable in milk samples 6 h after the oral dose. The mean concentration of serum ABZ was 63.7 ± 11.9 ng ml−1. The pharmacokinetic parameters for ABSX were calculated as follows: 351.9 ± 32.4 ng ml−1, 6.9 ± 0.5 h, 12.4 ± 2.2 h and 5190.3 ± 482.8 ng*h ml−1 for Cmax, Tmax, t½ and AUC0–36, respectively. The milk-to-serum ratios (range) for ABZ and ABSX were 0.9 (0.2–6.5) and 0.6 (0.1–1.5), respectively. CONCLUSIONS After an oral dose of 400 mg, ABZ and ABSX attain low concentrations in breast milk that are unlikely to be considered harmful for the breastfed infant. PMID:19916998

  3. Stereoselective interaction between the R enantiomer of warfarin and cimetidine.

    PubMed Central

    Choonara, I A; Cholerton, S; Haynes, B P; Breckenridge, A M; Park, B K

    1986-01-01

    The stereoselectivity of the pharmacokinetic interaction between warfarin and cimetidine was investigated in eight healthy volunteers. The warfarin enantiomers were given separately as single doses (15 mg) alone and during chronic administration of cimetidine (1 g day-1). Cimetidine did not interact with S warfarin but there was an interaction with the R enantiomer of warfarin. Cimetidine caused a significant increase in the mean plasma half-life of R warfarin (from 47.8 h to 57.8 h) and a significant decrease in its mean plasma clearance (from 2.3 to 1.7 ml h-1 kg-1) (P less than 0.02). Administration of a pharmacological dose of vitamin K1 together with the enantiomers of warfarin was necessary clinically and resulted in elevation of vitamin K1 2,3-epoxide concentrations, which were similar in each case. PMID:2938614

  4. Influence of glutamic acid enantiomers on C-mineralization.

    PubMed

    Formánek, Pavel; Vranová, Valerie; Lojková, Lea

    2015-02-01

    Seasonal dynamics in the mineralization of glutamic acid enantiomers in soils from selected ecosystems was determined and subjected to a range of treatments: ambient x elevated CO2 level and meadow x dense x thinned forest environment. Mineralization of glutamic acid was determined by incubation of the soil with 2 mg L- or D-glutamic acid g(-1) of dry soil to induce the maximum respiration rate. Mineralization of glutamic acid enantiomers in soils fluctuates over the course of a vegetation season, following a similar trend across a range of ecosystems. Mineralization is affected by environmental changes and management practices, including elevated CO2 level and thinning intensity. L-glutamic acid metabolism is more dependent on soil type as compared to metabolism of its D-enantiomer. The results support the hypothesis that the slower rate of D- compared to L- amino acid mineralization is due to different roles in anabolism and catabolism of the soil microbial community.

  5. C-H Coupling Reactions Directed by Sulfoxides: Teaching an Old Functional Group New Tricks.

    PubMed

    Pulis, Alexander P; Procter, David J

    2016-08-16

    Sulfoxides are classical functional groups for directing the stoichiometric metalation and functionalization of C-H bonds. In recent times, sulfoxides have been given a new lease on life owing to the development of modern synthetic methods that have arisen because of their unique reactivity. They have recently been used in catalytic C-H activation proceeding via coordination of an internal sulfoxide to a metal or through the action of an external sulfoxide ligand. Furthermore, sulfoxides are able to capture nucleophiles and electrophiles to give sulfonium salts, which subsequently enable the formation of C-C bonds at the expense of C-H bonds. This Review summarizes a renaissance period in the application of sulfoxides arising from their versatility in directing C-H functionalization. PMID:27409984

  6. Enantiomers resolution in capillary zone electrophoresis by using cyclodextrins.

    PubMed

    Schutzner, W; Fanali, S

    1992-01-01

    Cyclodextrins added to the background electrolyte are shown to be useful for the resolution of racemic compounds in their enantiomers. Several parameters have to be controlled in order to achieve resolution, e.g., cyclodextrin type, concentration, analyte shape, as well as column temperature. The resolution of nor-epinephrine, epinephrine and isoproterenol in their enantiomers decreased by increasing the column temperature. Octopamine and ketamine have been resolved by supporting the background electrolyte with 2, 6-di-O-methyl-beta-cyclodextrin. In spite of the stronger inclusion-complex of ketamine than octopamine with the modified cyclodextrin its resolution was not satisfactory.

  7. Simplified Production of Organic Compounds Containing High Enantiomer Excesses

    NASA Technical Reports Server (NTRS)

    Cooper, George W. (Inventor)

    2015-01-01

    The present invention is directed to a method for making an enantiomeric organic compound having a high amount of enantiomer excesses including the steps of a) providing an aqueous solution including an initial reactant and a catalyst; and b) subjecting said aqueous solution simultaneously to a magnetic field and photolysis radiation such that said photolysis radiation produces light rays that run substantially parallel or anti-parallel to the magnetic field passing through said aqueous solution, wherein said catalyst reacts with said initial reactant to form the enantiomeric organic compound having a high amount of enantiomer excesses.

  8. Interconversion of stereochemically labile enantiomers (enantiomerization).

    PubMed

    Trapp, Oliver

    2013-01-01

    The investigation of the molecular dynamics of stereoisomers is of fundamental interest in chemistry, biochemistry, medicine, and related areas. In recent years enantioselective dynamic chromatography and enantioselective dynamic capillary electrophoresis (DCE) have been established as versatile tools to investigate the kinetics of interconversions of stereoisomers. The term dynamic chromatography and dynamic electrophoresis, following the term dynamic NMR (DNMR) (Grathwohl and Wüthrich, Biopolymers 20:2623-2633, 1981; Wüthrich, Angew Chem Int Ed 42:3340-3363, 2003; Binsch et al., Angew Chem Int Ed 10:570-572, 1971), stresses the dynamic (Herschbach, Angew Chem Int Ed 26:1221-1243, 1987) behavior of analytes to interconvert between two stereoisomeric forms during the separation process. If the interconversion process is slow compared to the separation of the enantiomers, which can be achieved by accelerating the separation process or lowering the temperature, partial separation with characteristic plateau formation or peak broadening is observed.This chapter gives an overview of recent advances in the study of stereodynamics of molecules by dynamic chromatography (Trapp et al., Chirality 13:403-414, 2001; D'Acquarica et al., J Sep Sci 29:1508-1516, 2006; Wolf, Chem Soc Rev 34:595-608, 2005; Wolf, Dynamic stereochemistry of chiral compounds - principles and applications. RSC Publishing, Cambridge, 2008) and capillary electrophoresis. Models and algorithms to evaluate interconversion profiles obtained by separation techniques are discussed with respect to the challenging demands of high separation efficiencies typical of modern separation techniques. Models used for evaluation are based on iterative computer simulation algorithms using the theoretical plate model (TPM) or stochastic model of chromatography, empirical calculation methods, derived from equations used in chemical engineering, namely Damköhler analysis, and direct access using the approximation

  9. Chromatographic Separations of Enantiomers and Underivatized Oligosaccharides

    SciTech Connect

    Liu, Ying

    2004-01-01

    My graduate research has focused on separation science and bioanalytical analysis, which emphasized in method development. It includes three major areas: enantiomeric separations using high performance liquid chromatography (HPLC), Super/subcritical fluid chromatography (SFC), and capillary electrophoresis (CE); drug-protein binding behavior studies using CE; and carbohydrate analysis using liquid chromatograph-electrospray ionization mass spectrometry (LC-ESI-MS). Enantiomeric separations continue to be extremely important in the pharmaceutical industry. An in-depth evaluation of the enantiomeric separation capabilities of macrocyclic glycopeptides CSPs with SFC mobile phases was investigated using a set of over 100 chiral compounds. It was found that the macrocyclic based CSPs were able to separate enantiomers of various compounds with different polarities and functionalities. Seventy percent of all separations were achieved in less than 4 min due to the high flow rate (4.0 ml/min) that can be used in SFC. Drug-protein binding is an important process in determining the activity and fate of a drug once it enters the body. Two drug/protein systems have been studied using frontal analysis CE method. More sensitive fluorescence detection was introduced in this assay, which overcame the problem of low sensitivity that is common when using UV detection for drug-protein studies. In addition, the first usage of an argon ion laser with 257 nm beam coupled with CCD camera as a frontal analysis detection method enabled the simultaneous observation of drug fluorescence as well as the protein fluorescence. LC-ESI-MS was used for the separation and characterization of underivatized oligosaccharide mixtures. With the limits of detection as low as 50 picograms, all individual components of oligosaccharide mixtures (up to 11 glucose-units long) were baseline resolved on a Cyclobond I 2000 column and detected using ESI-MS. This system is characterized by high chromatographic

  10. Albendazole and colchicine modulate LPS-induced secretion of inflammatory mediators by liver macrophages.

    PubMed

    Viktorov, A V; Yurkiv, V A

    2011-10-01

    Colchicine and albendazole inhibited LPS-induced secretion of TNF-α and NO in a primary culture of rat Kupffer cells. Both agents potentiated the stimulating effect of this toxin on prostaglandin E2 secretion. The amount of prostaglandin D2 remained unchanged under these conditions. PMID:22485207

  11. Successful Treatment of Disseminated Anncaliia algerae Microsporidial Infection With Combination Fumagillin and Albendazole

    PubMed Central

    Boileau, Mélissa; Ferreira, José; Ahmad, Imran; Lavallée, Christian; Qvarnstrom, Yvonne; Dufresne, Simon F.

    2016-01-01

    Anncaliia algerae myositis is a life-threatening, emerging microsporidiosis among immunocompromised hosts. We report a case of disseminated A algerae infection in a man previously treated with alemtuzumab. Due to failure of albendazole-based therapy, fumagillin was added as a novel approach to management, with a good clinical response and patient survival. PMID:27704013

  12. Assessments of pharmacokinetic drug interactions and tolerability of albendazole, praziquantel and ivermectin combinations.

    PubMed

    Na-Bangchang, K; Kietinun, S; Pawa, K K; Hanpitakpong, W; Na-Bangchang, C; Lazdins, J

    2006-04-01

    The pharmacokinetic interactions and tolerability of albendazole, praziquantel and ivermectin combinations were assessed in 23 healthy Thai volunteers (12 males and 11 females). The study was an open, randomised, three-way crossover design in which each subject attended the study on three separate occasions (Phases I, II and III), of 4 d or 8 d each, with at least 1 or 2 weeks (but not longer than 2 months) between each phase. All subjects received the three study drug regimens as follows: regimen I, oral praziquantel (40 mg/kg body weight); regimen II, oral ivermectin (200 microg/kg body weight) given concurrently with an oral dose of albendazole (400 mg); and regimen III, oral ivermectin given concurrently with albendazole and praziquantel. All treatment regimens showed acceptable tolerability profiles. The incidence of overall drug-related adverse events was significantly higher following regimens I (12/23) and III (7/23) compared with that following regimen II (0/23). Six statistically significant changes in the pharmacokinetic parameters of albendazole sulphoxide (Cmax, AUC0-infinity, Vz/F, CL/F), praziquantel (Vz/F) and ivermectin (AUC0-infinity) were observed when the three drugs were given concurrently. However, based on US Food and Drug Administration criteria, these changes were not considered of clinical relevance. PMID:16271272

  13. Comparative trials using albendazole and mebendazole in the treatment of soil-transmitted helminths in schoolchildren on Penang, Malaysia.

    PubMed

    Rahman, W A

    1996-12-01

    Trials using albendazole and mebendazole, as single 400 mg dose treatments, against soil-transmitted helminths, were carried out in 7-9 and 10-12 years-old schoolchildren living in urban and rural environments in Penang, Malaysia. Both drugs were equally effective in treating trichuriasis and ascariasis in both age groups and environments. However, mebendazole is not so effective in the treatment for hookworms when compared to albendazole. It is suggested that albendazole should be considered the drug of choice for mass chemotherapy for Penang.

  14. Comparison of dissolution profiles for albendazole tablets using USP apparatus 2 and 4.

    PubMed

    Hurtado y de la Peña, Marcela; Vargas Alvarado, Yolanda; Domínguez-Ramírez, Adriana Miriam; Cortés Arroyo, Alma Rosa

    2003-08-01

    The in vitro dissolution of albendazole from three different commercially available products (200 mg tablets) was studied using U.S. Pharmacopeia (USP) Apparatus 2 and USP Apparatus 4 in order to compare the release performance of the drug in two essentially different dissolution systems. For both cases, 0.1 N HCl was used as dissolution medium. Only the reference product and one of the generic products studied met the 80% USP 24 specification for albendazole dissolved at 30 min, using USP Apparatus 2. Although the reference product reached 80% of albendazole dissolved at 30 min when Apparatus 4 was used, the generic products' dissolution performance was markedly reduced in this system. Though dissolution rate was slower using Apparatus 4, the total quantity of albendazole dissolved from the reference product, represented by area under the dissolution profile, was practically the same regardless of the system used. Dissolution kinetics of albendazole was adequately described by Weibull's function for all the products. The dissolution time (t(d)) derived from data fitting to this function showed significant differences among the products studied. Data analysis based on analysis of variance (ANOVA) showed nonequivalence among the dissolution profiles of generic products compared with the reference product either with the dissolution vessel system or the flow-through cell, as well as nonequivalence among the dissolution profiles using both apparatuses with the same product. Though differences in the dissolution profiles for generic products against the reference product in both systems were found, USP Apparatus 4 showed higher discriminative capacity in differentiating the release characteristics of the products tested. PMID:12906335

  15. A Review of Use of Enantiomers in Homeopathy

    PubMed Central

    Kuzeff, R. M.

    2012-01-01

    This paper reviews publications of laboratory experiments using pairs of enantiomers in homeopathy. Many molecules in nature have geometry which enables them to exist as nonsuperimposable mirror images or enantiomers. Modulation of toxicity of such molecules provides possibility for therapeutics, since they target multiple points in biochemical pathways. It was hypothesized that toxicity of a chemical agent could be counteracted by a homeopathic preparation of the enantiomer of the chemical agent (patents applied for: PCT/AU2003/000219-PCT/AU2008/001611). A diverse body of data, including controlled laboratory studies, supports the conclusion that toxicity of optical isomers may be inhibited by homeopathic enantiomer preparations. These data were obtained with minimal or no pretesting to determine optimal test solutions. Inhibition of the excitotoxic neurotransmitter L-glutamic acid with homeopathic preparations of D-glutamic acid indicates the latter may be of use for amelioration of symptoms of disturbances of mood. Similarly, homeopathic preparation of (+)-nicotine may be of use for inhibition of effects of nicotine in tobacco. PMID:23724294

  16. Plasma pharmacokinetics of warfarin enantiomers in cats.

    PubMed

    Smith, S A; Kraft, S L; Lewis, D C; Freeman, L C

    2000-12-01

    The purpose of this study was to determine the dispositions of S-warfarin and R-warfarin in normal cats following intravenous and oral administrations of racemic warfarin. Citrated blood samples were collected from 10 cats prior to and at times 5, 15, and 30 min, 1, 2, 3, 4, 5, 6, 12, 24, 36, 48, 72, 96, and 120 h following a single intravenous bolus of 0.5 mg/kg of racemic warfarin. After a 21-day washout period, samples were then similarly collected in three groups of four cats for 120 h following oral administration of 0.1, 0.25, and 0.5 mg/kg racemic warfarin. S-warfarin and R-warfarin were detected using a high-performance liquid chromatography assay validated for cat plasma. Drug concentration-time curves were subjected to non-compartmental analysis. Median pharmacokinetic parameters associated with the intravenous administration of 0.5 mg/kg racemic warfarin were as follows: t1/2 (S:28.2, R:18.3 h), area under the plasma concentration-time curve (AUC; S:33.0, R:24.6 h*microg/mL), area under the moment curve (AUMC; S:1889, R:527.8 h*h*microg/mL), and mean residence time (MRT; S:38.7, R:20.9 h). For each parameter, S-warfarin was significantly different from R-warfarin (P<0.05). Warfarin was absorbed rapidly after oral administration, and the dosage did not affect the time to maximum concentration (S:0.87, R:0.75 h). Oral dosage significantly influenced maximum plasma concentration (ng/mL, S:1267, R:1355 at 0.5 mg/kg; S:614.9, R:679.4 at 0.25 mg/kg; S:250.5, R:367.6 at 0.1 mg/kg), AUC (h*microg/mL, S:45.12, R:30.91 at 0.5 mg/kg; S:22.98:, R:18.99 at 0.25 mg/kg; S:3.922, R:3.570 at 0.1 mg/kg) and AUMC (h*h*microg/mL, S:2135, R:1062 at 0.5 mg/kg; S:943.1, R:599.9 at 0.25 mg/kg; S:132.2, R:59.03 at 0.1 mg/kg), but not t1/2 (S:23.5, R:11.6 h) nor MRT (S:26.3, R:13.5 h). Both warfarin enantiomers were highly (>96.5%) protein-bound. Quantitation of the warfarin content in commercially available tablets indicated an unequal distribution of the drug throughout the

  17. Acidity of Strong Acids in Water and Dimethyl Sulfoxide.

    PubMed

    Trummal, Aleksander; Lipping, Lauri; Kaljurand, Ivari; Koppel, Ilmar A; Leito, Ivo

    2016-05-26

    Careful analysis and comparison of the available acidity data of HCl, HBr, HI, HClO4, and CF3SO3H in water, dimethyl sulfoxide (DMSO), and gas-phase has been carried out. The data include experimental and computational pKa and gas-phase acidity data from the literature, as well as high-level computations using different approaches (including the W1 theory) carried out in this work. As a result of the analysis, for every acid in every medium, a recommended acidity value is presented. In some cases, the currently accepted pKa values were revised by more than 10 orders of magnitude. PMID:27115918

  18. Enantioselective DNA condensation induced by heptameric lanthanum helical supramolecular enantiomers.

    PubMed

    Bao, Fei-Fei; Xu, Xin-Xin; Zhou, Wen; Pang, Chun-Yan; Li, Zaijun; Gu, Zhi-Guo

    2014-09-01

    DNA condensation induced by a pair of heptameric La(III) helical enantiomers M-[La7(S-L)6(CO3)(NO3)6(OCH3)(CH3OH)7]·2CH3OH·5H2O and P-[La7(R-L)6(CO3)(NO3)6(OCH3)(CH3OH)5(H2O)2]·2CH3OH·4H2O (M-La and P-La, L=2-(2-hydroxybenzylamino)-3-carbamoylpropanoic acid) has been investigated by UV/vis spectroscopy, fluorescence spectroscopy, CD spectroscopy, EMSA, RALS, DLS, and SEM. The enantiomers M-La and P-La could induce CT-DNA condensation at a low concentration as observed in UV/vis spectroscopy. DNA condensates possessed globular nanoparticles with nearly homogeneous sizes in solid state determined by SEM (ca. 250 nm for M-La and ca. 200 nm for P-La). The enantiomers bound to DNA through electrostatic attraction and hydrogen bond interactions in a major groove, and rapidly condensed free DNA into its compact state. DNA decompaction has been acquired by using EDTA as disassembly agent, and analyzed by UV/vis spectroscopy, CD spectroscopy and EMSA. Moreover, the enantiomers M-La and P-La displayed discernible discrimination in DNA interaction and DNA condensation, as well as DNA decondensation. Our study suggested that lanthanum(III) enantiomers M-La and P-La were efficient DNA packaging agents with potential applications in gene delivery.

  19. Evaluation of the Impact of Excipients and an Albendazole Salt on Albendazole Concentrations in Upper Small Intestine Using an In Vitro Biorelevant Gastrointestinal Transfer (BioGIT) System.

    PubMed

    Kourentas, Alexandros; Vertzoni, Maria; Khadra, Ibrahim; Symillides, Mira; Clark, Hugh; Halbert, Gavin; Butler, James; Reppas, Christos

    2016-09-01

    An in vitro biorelevant gastrointestinal transfer (BioGIT) system was assessed for its ability to mimic recently reported albendazole concentrations in human upper small intestine after administration of free base suspensions to fasted adults in absence and in presence of supersaturation promoting excipients (hydroxypropylmethylcellulose and lipid self-emulsifying vehicles). The in vitro method was also used to evaluate the likely impact of using the sulfate salt on albendazole concentrations in upper small intestine. In addition, BioGIT data were compared with equilibrium solubility data of the salt and the free base in human aspirates and biorelevant media. The BioGIT system adequately simulated the average albendazole gastrointestinal transfer process and concentrations in upper small intestine after administration of the free base suspensions to fasted adults. However, the degree of supersaturation observed in the duodenal compartment was greater than in vivo. Albendazole sulfate resulted in minimal increase of albendazole concentrations in the duodenal compartment of the BioGIT, despite improved equilibrium solubility observed in human aspirates and biorelevant media, indicating that the use of a salt is unlikely to lead to any significant oral absorption advantage for albendazole. PMID:27372549

  20. Evaluation of the Impact of Excipients and an Albendazole Salt on Albendazole Concentrations in Upper Small Intestine Using an In Vitro Biorelevant Gastrointestinal Transfer (BioGIT) System.

    PubMed

    Kourentas, Alexandros; Vertzoni, Maria; Khadra, Ibrahim; Symillides, Mira; Clark, Hugh; Halbert, Gavin; Butler, James; Reppas, Christos

    2016-09-01

    An in vitro biorelevant gastrointestinal transfer (BioGIT) system was assessed for its ability to mimic recently reported albendazole concentrations in human upper small intestine after administration of free base suspensions to fasted adults in absence and in presence of supersaturation promoting excipients (hydroxypropylmethylcellulose and lipid self-emulsifying vehicles). The in vitro method was also used to evaluate the likely impact of using the sulfate salt on albendazole concentrations in upper small intestine. In addition, BioGIT data were compared with equilibrium solubility data of the salt and the free base in human aspirates and biorelevant media. The BioGIT system adequately simulated the average albendazole gastrointestinal transfer process and concentrations in upper small intestine after administration of the free base suspensions to fasted adults. However, the degree of supersaturation observed in the duodenal compartment was greater than in vivo. Albendazole sulfate resulted in minimal increase of albendazole concentrations in the duodenal compartment of the BioGIT, despite improved equilibrium solubility observed in human aspirates and biorelevant media, indicating that the use of a salt is unlikely to lead to any significant oral absorption advantage for albendazole.

  1. SWELLING OF PEATS IN LIQUID METHYL, TETRAMETHYLENE AND PROPYL SULFOXIDES AND IN LIQUID PROPYL SULFONE

    EPA Science Inventory

    The interactions of methyl, tetramethylene, and propyl sulfoxides and propyl sulfone during sorption onto four de-waxed, acid-form peats have been studied by means of swelling measurements. The results for sulfoxides are displayed as het-eromolecular sorption isotherms, which plo...

  2. Trifluoromethyl sulfoxides from allylic alcohols and electrophilic SCF3 donor by [2,3]-sigmatropic rearrangement.

    PubMed

    Maeno, Mayaka; Shibata, Norio; Cahard, Dominique

    2015-04-17

    An electrophilic trifluoromethylthiolation of allylic alcohols produces the corresponding allylic trifluoromethanesulfenates, which spontaneously rearrange into trifluoromethyl sulfoxides via a [2,3]-sigmatropic rearrangement. The reaction is straightforward and proceeds in good to high yields for the preparation of various allylic trifluoromethyl sulfoxides.

  3. FT-IR SOLUTION SPECTRA OF PROPYL SULFIDE, PROPYL SULFOXIDE, AND PROPYL SULFONE

    EPA Science Inventory

    FT-IR spectra were obtained of 0.5% volumetric solutions of propyl sulfide, propyl sulfoxide, and propyl sulfone in hexane, CCl4, CS2, and CHCl3 to assist in the assignment of FT-IR-PAS spectra of propyl sulfoxide sorbed within the structure of several peats and onto cellulose. T...

  4. Determination of the specific activities of methionine sulfoxide reductase A and B by capillary electrophoresis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A capillary electrophoresis (CE) method for the determination of methionine sulfoxide reductase A and methionine sulfoxide reductase B activities in mouse liver is described. The method is based on detection of the 4-(dimethylamino)azobenzene-4’-sulfonyl derivative of L-methionine (dabsyl Met), the ...

  5. tert-Butyl Sulfoxide as a Starting Point for the Synthesis of Sulfinyl Containing Compounds.

    PubMed

    Wei, Juhong; Sun, Zhihua

    2015-11-01

    Sulfoxides bearing a tert-butyl group can be activated using N-bromosuccinimide (NBS) under acidic conditions and then subsequently treated with a variety of nitrogen, carbon, or oxygen nucleophiles to afford a wide range of the corresponding sulfinic acid amides, new sulfoxides, and sulfinic acid esters. PMID:26502058

  6. Lithium solvation in dimethyl sulfoxide-acetonitrile mixtures

    SciTech Connect

    Semino, Rocío; Zaldívar, Gervasio; Calvo, Ernesto J.; Laria, Daniel

    2014-12-07

    We present molecular dynamics simulation results pertaining to the solvation of Li{sup +} in dimethyl sulfoxide-acetonitrile binary mixtures. The results are potentially relevant in the design of Li-air batteries that rely on aprotic mixtures as solvent media. To analyze effects derived from differences in ionic size and charge sign, the solvation of Li{sup +} is compared to the ones observed for infinitely diluted K{sup +} and Cl{sup −} species, in similar solutions. At all compositions, the cations are preferentially solvated by dimethyl sulfoxide. Contrasting, the first solvation shell of Cl{sup −} shows a gradual modification in its composition, which varies linearly with the global concentrations of the two solvents in the mixtures. Moreover, the energetics of the solvation, described in terms of the corresponding solute-solvent coupling, presents a clear non-ideal concentration dependence. Similar nonlinear trends were found for the stabilization of different ionic species in solution, compared to the ones exhibited by their electrically neutral counterparts. These tendencies account for the characteristics of the free energy associated to the stabilization of Li{sup +}Cl{sup −}, contact-ion-pairs in these solutions. Ionic transport is also analyzed. Dynamical results show concentration trends similar to those recently obtained from direct experimental measurements.

  7. In-vitro susceptibility of Giardia lamblia to albendazole, mebendazole and other chemotherapeutic agents.

    PubMed

    Cedillo-Rivera, R; Muñoz, O

    1992-09-01

    The susceptibility of a strain of Giardia lamblia to benzimidazole carbamates, 5-nitroimidazoles, nitrofurans and other drugs was studied in vitro. Albendazole was the most active compound, with a 50% inhibitory concentration (IC50) of 0.01 mg/L and a minimal lethal concentration (MLC) of less than 0.04 mg/L; the IC50 of mebendazole was 0.06 mg/L and the MLC less than 0.5 mg/L. Among the 5-nitroimidazoles tested, ornidazole was the most effective (IC50 0.12 mg/L); tinidazole, metronidazole, secnidazole and hemezole were less active. Nifuroxazide, etofamide and nalidixic acid exhibited modest anti-giardial activity; quinfamide did not inhibit the growth of the parasite at a concentration of 200 mg/L. Albendazole and mebendazole are promising candidates for clinical use and should be further evaluated.

  8. Influence of diet on the pattern of gastrointestinal biotransformation of netobimin and albendazole sulphoxide in sheep.

    PubMed

    Virkel, G; Lifschitz, A; Pis, A; Lanusse, C

    1999-01-01

    The in vitro biotransformation of the anthelmintic compounds, netobimin (NTB) pro-drug and albendazole sulphoxide (ABZSO), by ruminal fluid obtained from sheep fed either hay or concentrate-based diets was investigated. No metabolic activity was observed in boiled samples of ruminal fluid, which confirms the importance of ruminal microflora in the metabolism of the xenobiotics under investigation. NTB pro-drug was efficiently biotransformed by ruminal fluid in vitro. Albendazole (ABZ) and its sulphoxide derivative were the metabolic products recovered. The thioether ABZ was formed by sulphoreduction of ABZSO by ruminal fluid in vitro. A more efficient nitroreduction of NTB and sulphoreduction of ABZSO were observed for ruminal fluid collected from sheep fed the concentrate diet. The type of diet determines the composition and distribution of the microbial population in the rumen; this affects the pattern of drug biotransformation in the gastrointestinal tract, which may impact on drug therapy.

  9. Rationale for the coadministration of albendazole and ivermectin to humans for malaria parasite transmission control.

    PubMed

    Kobylinski, Kevin C; Alout, Haoues; Foy, Brian D; Clements, Archie; Adisakwattana, Poom; Swierczewski, Brett E; Richardson, Jason H

    2014-10-01

    Recently there have been calls for the eradication of malaria and the elimination of soil-transmitted helminths (STHs). Malaria and STHs overlap in distribution, and STH infections are associated with increased risk for malaria. Indeed, there is evidence that suggests that STH infection may facilitate malaria transmission. Malaria and STH coinfection may exacerbate anemia, especially in pregnant women, leading to worsened child development and more adverse pregnancy outcomes than these diseases would cause on their own. Ivermectin mass drug administration (MDA) to humans for malaria parasite transmission suppression is being investigated as a potential malaria elimination tool. Adding albendazole to ivermectin MDAs would maximize effects against STHs. A proactive, integrated control platform that targets malaria and STHs would be extremely cost-effective and simultaneously reduce human suffering caused by multiple diseases. This paper outlines the benefits of adding albendazole to ivermectin MDAs for malaria parasite transmission suppression.

  10. In-vitro susceptibility of Giardia lamblia to albendazole, mebendazole and other chemotherapeutic agents.

    PubMed

    Cedillo-Rivera, R; Muñoz, O

    1992-09-01

    The susceptibility of a strain of Giardia lamblia to benzimidazole carbamates, 5-nitroimidazoles, nitrofurans and other drugs was studied in vitro. Albendazole was the most active compound, with a 50% inhibitory concentration (IC50) of 0.01 mg/L and a minimal lethal concentration (MLC) of less than 0.04 mg/L; the IC50 of mebendazole was 0.06 mg/L and the MLC less than 0.5 mg/L. Among the 5-nitroimidazoles tested, ornidazole was the most effective (IC50 0.12 mg/L); tinidazole, metronidazole, secnidazole and hemezole were less active. Nifuroxazide, etofamide and nalidixic acid exhibited modest anti-giardial activity; quinfamide did not inhibit the growth of the parasite at a concentration of 200 mg/L. Albendazole and mebendazole are promising candidates for clinical use and should be further evaluated. PMID:1518040

  11. Effect of albendazole and mebendazole on soil-transmitted helminth eggs.

    PubMed

    Maipanich, W; Pubampen, S; Sa-nguankiat, S; Nontasut, P; Waikagul, J

    1997-06-01

    Primary school children from Nakhon Si Thammarat Province, Thailand, on endemic area of soil-transmitted helminths, were selected for study. The infected children were divided into two groups and pair-matched according to intensity of infections: group I were given albendazole (400mg) single dose and group II were given mebendazole (100mg) twice daily for 3 days. On the day following treatment, the number of Trichuris eggs in the stool markedly increased and the egg shape was also altered. These phenomena did not occur in Ascaris infections since 100% cure rate were obtained using both drugs. Incomplete ovicidal effect of the drugs to Trichuris and Ascaris eggs were demonstrated, embryos were observed to develop within the treated eggs and they hatched after feeding them to experimental animals. In hookworm infection, albendazole stimulated the females to release more eggs after medication, but both drugs showed complete ovicidal effect upon examining the eggs from the second bowel movement.

  12. A comparison of the efficacy of single doses of albendazole, ivermectin, and diethylcarbamazine alone or in combinations against Ascaris and Trichuris spp.

    PubMed Central

    Belizario, V. Y.; Amarillo, M. E.; de Leon, W. U.; de los Reyes, A. E.; Bugayong, M. G.; Macatangay, B. J. C.

    2003-01-01

    OBJECTIVE: To determine the efficacy of single doses of albendazole, ivermectin and diethylcarbamazine, and of the combinations albendazole + ivermectin and albendazole + diethylcarbamazine against common intestinal helminthiases caused by Ascaris and Trichuris spp. METHODS: In a randomized, placebo-controlled trial, infected children were randomly assigned to treatment with albendazole + placebo, ivermectin + placebo, diethylcarbamazine + placebo, albendazole + ivermectin, or albendazole + diethylcarbamazine. The Kato-Katz method was used for qualitative and quantitative parasitological diagnosis. The chi2 test was used to determine the significance of cure rates, repeated measures analysis of variance for the comparison of mean log egg counts, the Newman-Keuls procedure for multiple comparison tests, and logistic regression for the comparison of infection rates at days 180 and 360 after treatment. FINDINGS: Albendazole, ivermectin and the drug combinations gave significantly higher cure and egg reduction rates for ascariasis than diethylcarbamazine. For trichuriasis, albendazole + ivermectin gave significantly higher cure and egg reduction rates than the other treatments: the infection rates were lower 180 and 360 days after treatment. CONCLUSION: Because of the superiority of albendazole + ivermectin against both lymphatic filariasis and trichuriasis, this combination appears to be a suitable tool for the integrated or combined control of both public health problems. PMID:12640474

  13. Chiral Recognition Mechanisms in Enantiomers Separations: A General View

    NASA Astrophysics Data System (ADS)

    Berthod, Alain

    In 1858, Louis Pasteur, the first to accomplish the separation of two enantiomers wrote: “Most natural organic products, the essential products of life, are asymmetric and possess such asymmetry that they are not superimposable on their image. This establishes perhaps the only well-marked line of demarcation that can at present be drawn between the chemistry of dead matter and the chemistry of living matter.” Enantiomers have exactly the same properties in isotropic conditions. They behave differently only in anisotropic conditions. Chiral-chiral interactions are needed for enantiomeric separations. The fundamental mechanisms for chiral separations are listed along with the commercially available chiral selectors. Two chemometric examples are commented: one on quantitative structure enantioselectivity relationship and the second one on linear solvation energy relationships. It is shown that the solvents used in the mobile phase may play the most critical role in the chiral mechanism.

  14. Resolving enantiomers using the optical angular momentum of twisted light.

    PubMed

    Brullot, Ward; Vanbel, Maarten K; Swusten, Tom; Verbiest, Thierry

    2016-03-01

    Circular dichroism and optical rotation are crucial for the characterization of chiral molecules and are of importance to the study of pharmaceutical drugs, proteins, DNA, and many others. These techniques are based on the different interactions of enantiomers with circularly polarized components of plane wave light that carries spin angular momentum (SAM). For light carrying orbital angular momentum (OAM), for example, twisted or helical light, the consensus is that it cannot engage with the chirality of a molecular system as previous studies failed to demonstrate an interaction between optical OAM and chiral molecules. Using unique nanoparticle aggregates, we prove that optical OAM can engage with materials' chirality and discriminate between enantiomers. Further, theoretical results show that compared to circular dichroism, mainly based on magnetic dipole contributions, the OAM analog helical dichroism (HD) is critically dependent on fundamentally different chiral electric quadrupole contributions. Our work opens new venues to study chirality and can find application in sensing and chiral spectroscopy.

  15. Enantiomers of warfarin and vitamin K1 metabolism.

    PubMed Central

    Choonara, I A; Haynes, B P; Cholerton, S; Breckenridge, A M; Park, B K

    1986-01-01

    The effect of the individual enantiomers of warfarin at steady state (1 mg daily) was investigated in five healthy volunteers. Both enantiomers produced a significant increase in prothrombin time, but the increase with S warfarin (1.8 +/- 0.8 s, mean +/- s.d.) was greater than with R warfarin (1.0 +/- 0.3 s), despite lower steady state plasma concentrations of S warfarin, due to its more rapid clearance. Following the administration of vitamin K1, the maximum plasma concentration and area under the plasma concentration time curve values for the metabolite vitamin K1 2,3-epoxide were greater after S warfarin than after R warfarin. The greater anticoagulant potency of S warfarin is reflected by a greater degree of inhibition of vitamin K1 epoxide reductase. PMID:3567019

  16. Resolving enantiomers using the optical angular momentum of twisted light

    PubMed Central

    Brullot, Ward; Vanbel, Maarten K.; Swusten, Tom; Verbiest, Thierry

    2016-01-01

    Circular dichroism and optical rotation are crucial for the characterization of chiral molecules and are of importance to the study of pharmaceutical drugs, proteins, DNA, and many others. These techniques are based on the different interactions of enantiomers with circularly polarized components of plane wave light that carries spin angular momentum (SAM). For light carrying orbital angular momentum (OAM), for example, twisted or helical light, the consensus is that it cannot engage with the chirality of a molecular system as previous studies failed to demonstrate an interaction between optical OAM and chiral molecules. Using unique nanoparticle aggregates, we prove that optical OAM can engage with materials’ chirality and discriminate between enantiomers. Further, theoretical results show that compared to circular dichroism, mainly based on magnetic dipole contributions, the OAM analog helical dichroism (HD) is critically dependent on fundamentally different chiral electric quadrupole contributions. Our work opens new venues to study chirality and can find application in sensing and chiral spectroscopy. PMID:26998517

  17. Can enantiomers be separated in achiral chromatographic systems?

    NASA Astrophysics Data System (ADS)

    Davankov, V. A.

    2016-10-01

    Consideration of chromatography of a nonracemic mixture on an achiral sorbent from a stereochemical point of view allows the claim that partial separation of the excess enantiomer zone from the racemate zone is possible only with analytes capable of self-associating under the conditions of the chromatographic column. It is from these positions that features of this process can be explained and conditions for its maximal proceeding formulated.

  18. On the asymmetric adsorption of phenylalanine enantiomers by kaolin.

    NASA Technical Reports Server (NTRS)

    Bonner, W. A.; Flores, J.

    1973-01-01

    The attempt is described to verify a recent report that kaolin adsorbs D- and L-phenylalanine enantiomers to different extents from aqueous solutions at both pH 5.8 and pH 2. No evidence whatsoever could be found for the differential adsorption of D- versus L-phenylalanine by kaolin from either pH 6 or pH 2 solutions.

  19. Enantiomer Identification in Chiral Mixtures with Broadband Microwave Spectroscopy

    NASA Astrophysics Data System (ADS)

    Shubert, V. Alvin; Schmitz, David; Medcraft, Chris; Patterson, David; Doyle, John M.; Schnell, Melanie

    2014-06-01

    In nature and as products of chemical syntheses, chiral molecules often exist in mixtures with other chiral molecules. The analysis of these complex mixtures to identify the components, determine which enantiomers are present, and to measure the enantiomeric excesses (ee) is still one of the challenging but very important tasks of analytical chemistry. These analyses are required at every step of modern drug development, from candidate searches to production and regulation. We present here a new method of identifying individual enantiomers in mixtures of chiral molecules in the gas phase. It is based on broadband rotational spectroscopy and employs a sum or difference frequency generation three-wave mixing process that involves a closed cycle of three rotational transitions. The phase of the acquired signal bares the signature of the enantiomer (see figure), as it depends upon the combined quantity, μaμbμc, which is of opposite sign between members of an enantiomeric pair. Furthermore, because the signal amplitude is proportional to the ee, this technique allows for both determining which enantiomer is in excess and by how much. The high resolution of our technique allows us to perform molecule specific measurements of mixtures of chiral molecules with μaμbμc ≠ 0, even when the molecules are very similar (e.g. conformational isomers). We introduce the technique and present results on the analysis of mixtures of the terpenes, carvone, menthone, and carvomenthenol. D. Patterson, M. Schnell, J. M. Doyle, Nature. 497, 475-477, 2013 V. A. Shubert, D. Schmitz, D. Patterson, J. M. Doyle, M. Schnell, Ang. Chem. Int. Ed. 53, 1152-1155,2014

  20. Prevalence of intestinal protozoa infection among school-aged children on Pemba Island, Tanzania, and effect of single-dose albendazole, nitazoxanide and albendazole-nitazoxanide

    PubMed Central

    2013-01-01

    Background Pathogenic intestinal protozoa infections are common in school-aged children in the developing world and they are frequently associated with malabsorption syndromes and gastrointestinal morbidity. Since diagnosis of these parasites is difficult, prevalence data on intestinal protozoa is scarce. Methods We collected two stool samples from school-aged children on Pemba Island, Tanzania, as part of a randomized controlled trial before and 3 weeks after treatment with (i) single-dose albendazole (400 mg); (ii) single-dose nitazoxanide (1,000 mg); (iii) nitazoxanide-albendazole combination (1,000 mg–400 mg), with each drug given separately on two consecutive days; and (iv) placebo. Formalin-fixed stool samples were examined for the presence of intestinal protozoa using an ether-concentration method to determine the prevalence and estimate cure rates (CRs). Results Almost half (48.7%) of the children were diagnosed with at least one of the (potentially) pathogenic protozoa Giardia intestinalis, Entamoeba histolytica/E. dispar and Blastocystis hominis. Observed CRs were high for all treatment arms, including placebo. Nitazoxanide showed a significant effect compared to placebo against the non-pathogenic protozoon Entamoeba coli. Conclusions Intestinal protozoa infections might be of substantial health relevance even in settings where they are not considered as a health problem. Examination of a single stool sample with the ether-concentration method lacks sensitivity for the diagnosis of intestinal protozoa, and hence, care is indicated when interpreting prevalence estimates and treatment effects. PMID:23289920

  1. Supported oligomethionine sulfoxide and Ellman's reagent for cysteine bridges formation.

    PubMed

    Ronga, Luisa; Verdié, Pascal; Sanchez, Pierre; Enjabal, Christine; Maurras, Amélie; Jullian, Magalie; Puget, Karine; Martinez, Jean; Subra, Gilles

    2013-02-01

    A large number of bioactive peptides are cyclized through a disulfide bridge. This structural feature is very important for both bioactivity and stability. The oxidation of cysteine side chains is challenging not only to avoid intermolecular reaction leading to oligomers and oxidation of other residues but also to remove solvents and oxidant such as dimethyl sulfoxide. Supported reagents advantageously simplify the work-up of such disulfide bond formation, but may lead to a significant decrease in yield of the oxidized product. In this study, two resins working through different mechanisms were evaluated: Clear-Ox, a supported version of Ellman's reagent and Oxyfold, consisting in a series of oxidized methionine residues. The choice of the supported reagent is discussed on the light of reaction speed, side-products formation and yield considerations.

  2. Effects of dimethyl sulfoxide on lipid membrane electroporation.

    PubMed

    Fernández, M Laura; Reigada, Ramon

    2014-08-01

    Pores can be generated in lipid membranes by the application of an external electric field or by the addition of particular chemicals such as dimethyl sulfoxide (DMSO). Molecular dynamics (MD) has been shown to be a useful tool for unveiling many aspects of pore formation in lipid membranes in both situations. By means of MD simulations, we address the formation of electropores in cholesterol-containing lipid bilayers under the influence of DMSO. We show how a combination of physical and chemical mechanisms leads to more favorable conditions for generating membrane pores and, in particular, how the addition of DMSO to the medium significantly reduces the minimum electric field required to electroporate a lipid membrane. The strong alteration of membrane transversal properties and the energetic stabilization of the hydrophobic pore stage by DMSO provide the physicochemical mechanisms that explain this effect.

  3. Solubility properties of racemic praziquantel and its enantiomers.

    PubMed

    el-Arini, S K; Giron, D; Leuenberger, H

    1998-11-01

    The purpose of this study was to characterize the solubility and thermodynamic properties of the optical isomers of the anti-schistosomal drug, praziquantel (PZQ) and to compare these properties to those of the racemic product used in commercial preparations (Biltricide, generic drugs). The crystalline enantiomers of PZQ exhibited different thermal properties than the racemic drug. The melting points and the enthalpies of fusion obtained from the differential scanning calorimetry (DSC) scans were nearly identical between the isomers and were substantially lower than those of racemic PZQ [(+/-)-PZQ]. The DSC results indicate that (+/-)-PZQ is a racemic compound and not a racemic mixture. This was confirmed by powder x-ray diffraction analysis and the IR spectra. The 30 degrees decrease in the melting point was reflected in increased solubility of the enantiomers, which amounted to twice that of the racemic PZQ. The behavior of the isomers in the presence of beta-cyclodextrin (beta-CD) was studied in water at 37 degrees C. The solubility data (phase solubility diagrams) were linear for up to the highest concentration of added beta-CD investigated. The apparent stability constants determined from the phase solubility diagrams showed that both the (+) and (-) enantiomers as well as (+/-)-PZQ exhibited moderate affinity to form a 1:1 complex in solution with beta-CD. The findings of this study may be of importance when efforts are considered to improve pharmaceutical formulation of this anti-schistosomal drug. PMID:9834959

  4. Toxicity and bioaccumulation of ethofumesate enantiomers in earthworm Eisenia fetida.

    PubMed

    Xu, Peng; Wang, Yinghuan; Zhang, Yanfeng; Li, Jianzhong; Wang, Huili

    2014-10-01

    Earthworms represent an important food source for many vertebrates and as a result, predators may encounter toxic effects via the food chain from consumption of contaminated worms. Therefore, including an assessment of xenobiotic to worms in risk assessment procedures is advisable. Here we studied the acute toxicity, bioaccumulation and elimination of ethofumesate enantiomers in earthworm, Eisenia fetida, in a soil. A slight difference in toxicity to earthworm between two enantiomers was found, and the calculated LC50 values for (+)-, rac- and (-)-ethofumesate were 4.51, 5.93 and 7.98 μg/cm(2), respectively, indicating that the acute toxicity of ethofumesate enantiomers was enantioselective. Earthworm can uptake ethofumesate but the bioaccumulation curve did not reach the steady state. In the elimination experiment, the concentrations of ethofumesate in earthworm declined following a first-order decay model with a short half life of 1.8d. The bioaccumulation and elimination of ethofumesate in earthworm were both nonenantioselective. In combination with other studies, a linear relationship between Log BSAFs and Log Kow was observed, and the Log BSAFs increased with increasing Log Kow. But the elimination rate did not show any correlation with the Kow value.

  5. Stereoselective metabolism of tetrahydropalmatine enantiomers in rat liver microsomes.

    PubMed

    Zhao, Ming; Li, Li-Ping; Sun, Dong-Li; Sun, Si-Yuan; Huang, Shan-Ding; Zeng, Su; Jiang, Hui-Di

    2012-05-01

    Tetrahydropalmatine (THP), with one chiral center, is an active alkaloid ingredient in Rhizoma Corydalis. The aim of the present paper is to study whether THP enantiomers are metabolized stereoselectively in rat, mouse, dog, and monkey liver microsomes, and then, to elucidate which Cytochrome P450 (CYP) isoforms are predominately responsible for the stereoselective metabolism of THP enantiomers in rat liver microsomes (RLM). The results demonstrated that (+)-THP was preferentially metabolized by liver microsomes from rats, mice, dogs, and monkeys, and the intrinsic clearance (Cl(int)) ratios of (+)-THP to (-)-THP were 2.66, 2.85, 4.24, and 1.67, respectively. Compared with the metabolism in untreated RLM, the metabolism of (-)-THP and (+)-THP was significantly increased in dexamethasone (Dex)-induced and β-naphthoflavone (β-NF)-induced RLM; meanwhile, the Cl(int) ratios of (+)-THP to (-)-THP in Dex-induced and β-NF-induced RLM were 5.74 and 0.81, respectively. Ketoconazole had stronger inhibitory effect on (+)-THP than (-)-THP, whereas fluvoxamine had stronger effect on (-)-THP in untreated and Dex-induced or β-NF-induced RLM. The results suggested that THP enantiomers were predominately metabolized by CYP3A1/2 and CYP1A2 in RLM, and CYP3A1/2 preferred to metabolize (+)-THP, whereas CYP1A2 preferred (-)-THP.

  6. Utilization of alternate chirality enantiomers in microbial communities

    NASA Astrophysics Data System (ADS)

    Pikuta, Elena V.; Hoover, Richard B.

    2010-09-01

    Our previous study of chirality led to interesting findings for some anaerobic extremophiles: the ability to metabolize substrates with alternate chirality enantiomers of amino acids and sugars. We have subsequently found that not just separate microbial species or strains but entire microbial communities have this ability. The functional division within a microbial community on proteo- and sugarlytic links was also reflected in a microbial diet with L-sugars and D-amino acids. Several questions are addressed in this paper. Why and when was this feature developed in a microbial world? Was it a secondary de novo adaptation in a bacterial world? Or is this a piece of genetic information that has been left in modern genomes as an atavism? Is it limited exclusively to prokaryotes, or does this ability also occur in eukaryotes? In this article, we have used a broader approach to study this phenomenon using anaerobic extremophilic strains from our laboratory collection. A series of experiments were performed on physiologically different groups of extremophilic anaerobes (pure and enrichment cultures). The following characteristics were studied: 1) the ability to grow on alternate chirality enantiomers - L-sugars and D- amino acids; 2) Growthinhibitory effect of alternate chirality enantiomers; 3) Stickland reaction with alternate chirality amino acids. The results of this research are presented in this paper.

  7. Utilization of Alternate Chirality Enantiomers in Microbial Communities

    NASA Technical Reports Server (NTRS)

    Pikuta, Elena V.; Hoover, Richard B.

    2010-01-01

    Our previous study of chirality led to interesting findings for some anaerobic extremophiles: the ability to metabolize substrates with alternate chirality enantiomers of amino acids and sugars. We have subsequently found that not just separate microbial species or strains but entire microbial communities have this ability. The functional division within a microbial community on proteo- and sugarlytic links was also reflected in a microbial diet with L-sugars and D-amino acids. Several questions are addressed in this paper. Why and when was this feature developed in a microbial world? Was it a secondary de novo adaptation in a bacterial world? Or is this a piece of genetic information that has been left in modern genomes as an atavism? Is it limited exclusively to prokaryotes, or does this ability also occur in eukaryotes? In this article, we have used a broader approach to study this phenomenon using anaerobic extremophilic strains from our laboratory collection. A series of experiments were performed on physiologically different groups of extremophilic anaerobes (pure and enrichment cultures). The following characteristics were studied: 1) the ability to grow on alternate chirality enantiomers -- L-sugars and D- amino acids; 2) Growth-inhibitory effect of alternate chirality enantiomers; 3) Stickland reaction with alternate chirality amino acids. The results of this research are presented in this paper.

  8. Use of cyclodextrins in capillary electrophoresis: resolution of tramadol enantiomers.

    PubMed

    Rudaz, S; Veuthey, J L; Desiderio, C; Fanali, S

    1998-11-01

    Capillary zone electrophoresis was successfully applied to the enantiomeric resolution of racemic tramadol. Both uncoated and polyacrylamide-coated capillaries were tested for method optimization using either negatively charged or native cyclodextrins (CD) added to the background electrolyte (BGE). The resolution was strongly influenced by the CD type and concentration as well as by the pH and the concentration of the BGE. Among the CDs tested, carboxymethylated-beta-cyclodextrin allowed the baseline separation of tramadol enantiomers. After the method was optimized, it was validated in a coated capillary for enantiomeric analysis of tramadol enantiomers in pharmaceutical formulation, including specificity and elution order, linearity, accuracy and precision, determination of limit of detection (LOD) and quantification (LOQ), enantiomeric purity linearity, freedom from interference, and stability of sample solutions. Precision at the target concentration was less than 2%, with an accuracy higher than 99%. Furthermore, the method was able to detect 0.3% and to quantify 1% of the minor enantiomer in the presence of the major one at the target value.

  9. Bacterial dioxygenase- and monooxygenase-catalysed sulfoxidation of benzo[b]thiophenes.

    PubMed

    Boyd, Derek R; Sharma, Narain D; McMurray, Brian; Haughey, Simon A; Allen, Christopher C R; Hamilton, John T G; McRoberts, W Colin; O'Ferrall, Rory A More; Nikodinovic-Runic, Jasmina; Coulombel, Lydie A; O'Connor, Kevin E

    2012-01-28

    Asymmetric heteroatom oxidation of benzo[b]thiophenes to yield the corresponding sulfoxides was catalysed by toluene dioxygenase (TDO), naphthalene dioxygenase (NDO) and styrene monooxygenase (SMO) enzymes present in P. putida mutant and E. coli recombinant whole cells. TDO-catalysed oxidation yielded the relatively unstable benzo[b]thiophene sulfoxide; its dimerization, followed by dehydrogenation, resulted in the isolation of stable tetracyclic sulfoxides as minor products with cis-dihydrodiols being the dominant metabolites. SMO mainly catalysed the formation of enantioenriched benzo[b]thiophene sulfoxide and 2-methyl benzo[b]thiophene sulfoxides which racemized at ambient temperature. The barriers to pyramidal sulfur inversion of 2- and 3-methyl benzo[b]thiophene sulfoxide metabolites, obtained using TDO and NDO as biocatalysts, were found to be ca.: 25-27 kcal mol(-1). The absolute configurations of the benzo[b]thiophene sulfoxides were determined by ECD spectroscopy, X-ray crystallography and stereochemical correlation. A site-directed mutant E. coli strain containing an engineered form of NDO, was found to change the regioselectivity toward preferential oxidation of the thiophene ring rather than the benzene ring. PMID:22134441

  10. Transformation and adsorption of Fenamiphos, f. sulfoxide and f. sulfone in molokai soil and simulated movement with irrigation

    NASA Astrophysics Data System (ADS)

    Lee, Chee-Chow; Green, Richard E.; Apt, Walter J.

    1986-02-01

    The ban of commonly used soil fumigants, DBCP and EDB, for control of nematodes in pineapple fields has prompted investigations into a non-fumigant nematicide, fenamiphos (Nemacur ®). The transformation and adsorption in soil of fenamiphos and its transformation products, f. sulfoxide and f. sulfone were studied in the laboratory. Fenamiphos adsorption on soil exceeded that of f. sulfoxide and f. sulfone. F. sulfoxide, however, was the most persistent. A one-dimensional simulation model was used to assess the impact of transformation and adsorption on the mobility and distribution of fenamiphos and f. sulfoxide in soil. Simulated results showed that fenamiphos stayed in the topsoil and transformed rapidly to f. sulfoxide. Because of the persistence and mobility of f. sulfoxide, this metabolite leached rapidly and significant amounts remained in the soil. This suggests that for times exceeding three weeks, f. sulfoxide may be the dominant compound providing nematode control in drip-irrigated pineapple.

  11. Enhanced efficacy of sequential administration of Albendazole for the clearance of Wuchereria bancrofti infection: Double blind RCT.

    PubMed

    De Britto, R L; Vanamail, P; Sankari, T; Vijayalakshmi, G; Das, L K; Pani, S P

    2015-06-01

    Till today, there is no effective treatment protocol for the complete clearance of Wuchereria bancrofti (W.b) infection that causes secondary lymphoedema. In a double blind randomized control trial (RCT), 146 asymptomatic W. b infected individuals were randomly assigned to one of the four regimens for 12 days, DEC 300 mg + Doxycycline 100 mg coadministration or DEC 300 mg + Albendazole 400 mg co-administration or DEC 300 mg + Albendazole 400 mg sequential administration or control regimen DEC 300 mg and were followed up at 13, 26 and 52 weeks post-treatment for the clearance of infection. At intake, there was no significant variation in mf counts (F(3,137)=0.044; P=0.988) and antigen levels (F(3,137)=1.433; P=0.236) between the regimens. Primary outcome analysis showed that DEC + Albendazole sequential administration has an enhanced efficacy over DEC + Albendazole co-administration (80.6 Vs 64.7%), and this regimen is significantly different when compared to DEC + doxycycline co-administration and control (P<0.05), in clearing microfilaria in 13 weeks. Secondary outcome analysis showed that, all the trial regimens were comparable to control regimen in clearing antigen (F(3, 109)=0.405; P=0.750). Therefore, DEC + Albendazole sequential administration appears to be a better option for rapid clearance of W. b microfilariae in 13 weeks time. (Clinical trials.gov identifier - NCT02005653). PMID:26691247

  12. Does dimethyl sulfoxide increase protein immunomarking efficiency for dispersal and predation studies?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marking biological control agents facilitates studies of dispersal and predation. This study examines the effect of a biological solvent, dimethyl sulfoxide (DMSO), on retention of immunoglobulin G (IgG) protein solutions applied to Diorhabda carinulata (Desbrochers) (Coleoptera: Chrysomelidae) eit...

  13. Enantiomerization of Allylic Trifluoromethyl Sulfoxides Studied by HPLC Analysis and DFT Calculations.

    PubMed

    Bailly, Laetitia; Petit, Emilie; Maeno, Mayaka; Shibata, Norio; Trapp, Oliver; Cardinael, Pascal; Chataigner, Isabelle; Cahard, Dominique

    2016-02-01

    Enantiomerization of allylic trifluoromethyl sulfoxides occurs spontaneously at room temperature through the corresponding allylic trifluoromethanesulfenates via a [2,3]-sigmatropic rearrangement. Dynamic enantioselective high-performance liquid chromatography (HPLC) analysis revealed the stereodynamics of these sulfoxides ranging from chromatographic resolution to peak coalescence at temperatures between 5 and 53 °C. The rate constant of enantiomerization and activation parameters were determined and compared with Density Functional Theory (DFT) calculations.

  14. Chiral Separation of Indapamide Enantiomers by Capillary Electrophoresis

    PubMed Central

    Tero-Vescan, Amelia; Hancu, Gabriel; Oroian, Mihaela; Cârje, Anca

    2014-01-01

    Purpose: Indapamide is probably the most frequently prescribed diuretic drug, generally being used for the treatment of hypertension. It contains a chiral center in its molecule; is marketed as a racemic mixture; but there are rather few studies regarding the pharmacokinetic and the pharmacological effect differences of the two enantiomers. Our aim was the development of a simple, rapid and precise analytical procedure for the chiral separation of indapamide enantiomers. Methods: In this study capillary zone electrophoresis was used for the enantiomeric separation of indapamide using a systematic screening approach involving different native and derivatized; neutral and charged cyclodextrines as chiral selectors. The effects of pH value and composition of the background electrolyte, capillary temperature, running voltage and injection parameters have been investigated. Results: After preliminary analysis a charged derivatized CD, sulfobuthyl ether- β-CD, proved to be the optimum chiral selector for the enantioseparation. Using a buffer solution containing 25 mM disodium hydrogenophosphate – 25 mM sodium didydrogenophosphate and 5 mM sulfobuthyl ether- β-CD as chiral selector at a pH - 7, a voltage of + 25 kV, temperature 15°C and UV detection at 242 nm, we succeeded in the separation of the two enantiomers in approximately 6 minutes, with a resolution of 4.30 and a separation factor of 1.08. Conclusion: Capillary zone electrophoresis using cyclodextrines as chiral selectors proved to be a suitable method for the enantioseparation of indapamide. Our method is rapid, specific, reliable, and cost-effective and can be proposed for laboratories performing indapamide routine analysis. PMID:24754011

  15. Population pharmacokinetic analysis of Ibuprofen enantiomers in preterm newborn infants.

    PubMed

    Gregoire, Nicolas; Desfrere, Luc; Roze, Jean-Christophe; Kibleur, Yves; Koehne, Petra

    2008-12-01

    The aim of this pharmacokinetic analysis was to develop and validate a population pharmacokinetic model for R- and S-ibuprofen from samples obtained after 3 successive administrations of ibuprofen (10-5-5 mg/kg) at 24-hour intervals to preterm newborn infants aged from <6 hours to 8 days of life. A model including unilateral bioconversion of R-ibuprofen into S-ibuprofen was developed using the software NONMEM. R- and S-ibuprofen plasma concentrations were adequately fitted by this model. Estimated clearance and volume of distribution were 3.5 mL/h/kg and 173 mL/kg, respectively, with a calculated half-life (t((1/2))) of 34.3 hours for S-ibuprofen. Estimated clearance at birth and volume of distribution were 25.5 mL/h/kg and 306 mL/kg with a t((1/2)) at birth of 8.3 hours for R-ibuprofen. R-ibuprofen elimination increased during the first week of life, whereas S-ibuprofen pharmacokinetics were weakly modified. Therefore, because the activity of the 2 enantiomers differs, it is important that subsequent studies consider R- and S-enantiomers separately. Mean simulated ibuprofen concentrations at various dose regimens were in agreement with observed concentrations. The present analysis allows a more accurate estimation of the ibuprofen pharmacokinetics as parameters could be estimated separately for each enantiomer and the effect of postnatal age on the elimination of R-ibuprofen was elicited. PMID:18796580

  16. The discovery of methionine sulfoxide reductase enzymes: An historical account and future perspectives.

    PubMed

    Achilli, Cesare; Ciana, Annarita; Minetti, Giampaolo

    2015-05-01

    L-Methionine (L-Met) is the only sulphur-containing proteinogenic amino acid together with cysteine. Its importance is highlighted by it being the initiator amino acid for protein synthesis in all known living organisms. L-Met, free or inserted into proteins, is sensitive to oxidation of its sulfide moiety, with formation of L-Met sulfoxide. The sulfoxide could not be inserted into proteins, and the oxidation of L-Met in proteins often leads to the loss of biological activity of the affected molecule. Key discoveries revealed the existence, in rats, of a metabolic pathway for the reduction of free L-Met sulfoxide and, later, in Escherichia coli, of the enzymatic reduction of L-Met sulfoxide inserted in proteins. Upon oxidation, the sulphur atom becomes a new stereogenic center, and two stable diastereoisomers of L-Met sulfoxide exist. A fundamental discovery revealed the existence of two unrelated families of enzymes, MsrA and MsrB, whose members display opposite stereospecificity of reduction for the two sulfoxides. The importance of Msrs is additionally emphasized by the discovery that one of the only 25 selenoproteins expressed in humans is a Msr. The milestones on the road that led to the discovery and characterization of this group of antioxidant enzymes are recounted in this review.

  17. Effect of sulfoxides on the thermal denaturation of hen lysozyme: A calorimetric and Raman study

    NASA Astrophysics Data System (ADS)

    Torreggiani, A.; Di Foggia, M.; Manco, I.; De Maio, A.; Markarian, S. A.; Bonora, S.

    2008-11-01

    A multidisciplinary study of the thermal denaturation of lysozyme in the presence of three sulfoxides with different length in hydrocarbon chain (DMSO, DESO, and DPSO) was carried out by means of DSC, Raman spectroscopy, and SDS-PAGE techniques. In particular, the Td and Δ H values obtained from the calorimetric measurements showed that lysozyme is partially unfolded by sulfoxides but most of the conformation holds native state. The sulfoxide denaturing ability increases in the order DPSO > DESO > DMSO. Moreover, only DMSO and DESO have a real effect in preventing the heat-induced inactivation of the protein and their maximum heat-protective ability is reached when the DMSO and DESO amount is ⩾25% w/w. The sulfoxide ability to act as effective protective agents against the heat-induced inactivation was confirmed by the protein analysis. The enzymatic activity, as well as the SDS-PAGE analysis, suggested that DESO, having a low hydrophobic character and a great ability to stabilise the three-dimensional water structure, is the most heat-protective sulfoxide. An accurate evaluation of the heat-induced conformational changes of the lysozyme structure before and after sulfoxide addition was obtained by the analysis of the Raman spectra. The addition of DMSO or DESO in low concentration resulted to sensitively decrease the heat-induced structural modifications of the protein.

  18. Albendazole inhibits endothelial cell migration, tube formation, vasopermeability, VEGF receptor-2 expression and suppresses retinal neovascularization in ROP model of angiogenesis

    SciTech Connect

    Pourgholami, Mohammad H.; Khachigian, Levon M.; Fahmy, Roger G.; Badar, Samina; Wang, Lisa; Chu, Stephanie Wai Ling; Morris, David Lawson

    2010-07-09

    The angiogenic process begins with the cell proliferation and migration into the primary vascular network, and leads to vascularization of previously avascular tissues and organs as well to growth and remodeling of the initially homogeneous capillary plexus to form a new microcirculation. Additionally, an increase in microvascular permeability is a crucial step in angiogenesis. Vascular endothelial growth factor (VEGF) plays a central role in angiogenesis. We have previously reported that albendazole suppresses VEGF levels and inhibits malignant ascites formation, suggesting a possible effect on angiogenesis. This study was therefore designed to investigate the antiangiogenic effect of albendazole in non-cancerous models of angiogenesis. In vitro, treatment of human umbilical vein endothelial cells (HUVECs) with albendazole led to inhibition of tube formation, migration, permeability and down-regulation of the VEGF type 2 receptor (VEGFR-2). In vivo albendazole profoundly inhibited hyperoxia-induced retinal angiogenesis in mice. These results provide new insights into the antiangiogenic effects of albendazole.

  19. Albendazole and Corticosteroids for the Treatment of Solitary Cysticercus Granuloma: A Network Meta-analysis

    PubMed Central

    Nakajima, Hideaki; Huang, Tong-Yi; Sun, Kai-Yu; Chen, Shu-Ling; Chen, Ke-Bing

    2016-01-01

    Background Solitary cysticercus granuloma (SCG) is the commonest form of neurocysticercosis in the Indian subcontinent and in travelers. Several different treatment options exist for SCG. We conducted a Bayesian network meta-analysis of randomized clinical trials (RCTs) to identify the best treatment option to prevent seizure recurrence and promote lesion resolution for patients with SCG. Methods and Principal Findings PubMed, EMBASE and the Cochrane Library databases (up to June 1, 2015) were searched for RCTs that compared any anthelmintics or corticosteroids, alone or in combination, with placebo or head to head and reported on seizure recurrence and lesion resolution in patients with SCG. A total of 14 RCTs (1277 patients) were included in the quantitative analysis focusing on four different treatment options. A Bayesian network model computing odds ratios (OR) with 95% credible intervals (CrI) and probability of being best (Pbest) was used to compare all interventions simultaneously. Albendazole and corticosteroids combination therapy was the only regimen that significantly decreased the risk of seizure recurrence compared with conservative treatment (OR 0.32, 95% CrI 0.10–0.93, Pbest 73.3%). Albendazole and corticosteroids alone or in combination were all efficacious in hastening granuloma resolution, but the combined therapy remained the best option based on probability analysis (OR 3.05, 95% CrI 1.24–7.95, Pbest 53.9%). The superiority of the combination therapy changed little in RCTs with different follow-up durations and in sensitivity analyses. The limitations of this study include high risk of bias and short follow-up duration in most studies. Conclusions Dual therapy of albendazole and corticosteroids was the most efficacious regimen that could prevent seizure recurrence and promote lesion resolution in a follow-up period of around one year. It should be recommended for the management of SCG until more high-quality evidence is available. PMID

  20. Treatment of Bifocal Cyst Hydatid Involvement in Right Femur with Teicoplanin Added Bone Cement and Albendazole

    PubMed Central

    Pazarci, Ozhan; Oztemur, Zekeriya; Bulut, Okay

    2015-01-01

    Although bone involvement associated with cyst hydatid is rarely seen, it can cause unintended results such as high recurrence rate, infection, sepsis, or amputation of relevant extremity. Because of this reason, its treatment is difficult and disputed. In the case of bifocal bone cyst hydatid in right femur, along with albendazole treatment, result of resecting cyst surgically and its treatment with teicoplanin with added bone cement is given. In conclusion, since the offered treatment method both supports bone in terms of mechanical aspect and also can prevent secondary infection, the method is thought to be a good and safe treatment approach. PMID:26236523

  1. Supersensitive detection and discrimination of enantiomers by dorsal olfactory receptors: evidence for hierarchical odour coding.

    PubMed

    Sato, Takaaki; Kobayakawa, Reiko; Kobayakawa, Ko; Emura, Makoto; Itohara, Shigeyoshi; Kizumi, Miwako; Hamana, Hiroshi; Tsuboi, Akio; Hirono, Junzo

    2015-09-11

    Enantiomeric pairs of mirror-image molecular structures are difficult to resolve by instrumental analyses. The human olfactory system, however, discriminates (-)-wine lactone from its (+)-form rapidly within seconds. To gain insight into receptor coding of enantiomers, we compared behavioural detection and discrimination thresholds of wild-type mice with those of ΔD mice in which all dorsal olfactory receptors are genetically ablated. Surprisingly, wild-type mice displayed an exquisite "supersensitivity" to enantiomeric pairs of wine lactones and carvones. They were capable of supersensitive discrimination of enantiomers, consistent with their high detection sensitivity. In contrast, ΔD mice showed selective major loss of sensitivity to the (+)-enantiomers. The resulting 10(8)-fold differential sensitivity of ΔD mice to (-)- vs. (+)-wine lactone matched that observed in humans. This suggests that humans lack highly sensitive orthologous dorsal receptors for the (+)-enantiomer, similarly to ΔD mice. Moreover, ΔD mice showed >10(10)-fold reductions in enantiomer discrimination sensitivity compared to wild-type mice. ΔD mice detected one or both of the (-)- and (+)-enantiomers over a wide concentration range, but were unable to discriminate them. This "enantiomer odour discrimination paradox" indicates that the most sensitive dorsal receptors play a critical role in hierarchical odour coding for enantiomer identification.

  2. Disposition of enantiomers of sultopride in a human, rats and rabbits.

    PubMed

    Kamizono, A; Inotsume, N; Fukushima, S; Nakano, M

    1993-11-01

    Pharmacokinetics of sultopride enantiomers was examined following a single dose in a human, rabbits and rats. Pharmacokinetic profiles were similar between (+)- and (-)-enantiomers of sultopride in human, whereas the serum concentrations of (-)-sultopride were slightly higher than those of (+)-sultopride after i.v. administration of 50 mg/kg of racemic sultopride to rats and rabbits.

  3. Pure enantiomers of 2-arylpropionic acids: tools in pain research and improved drugs in rheumatology.

    PubMed

    Brune, K; Geisslinger, G; Menzel-Soglowek, S

    1992-10-01

    The mode of action of aspirinlike drugs in pain is widely referred to as inhibition of prostaglandin synthesis. Salicylic acid, however, at low doses, is an analgesic but not a potent anti-inflammatory agent. This "enigma" may be resolved by recent findings employing 2-arylpropionic acids. Pure enantiomers of these chiral drugs show a different pharmacodynamic and pharmacokinetic profile. Using pure enantiomers of flurbiprofen, ibuprofen, and ketoprofen, we could show that (1) R-enantiomers of these drugs are inverted to S-enantiomers to a different degree in different species, including humans, (2) the pharmacokinetic parameters of both pure enantiomers differ in a drug- and a species-specific manner, and (3) both enantiomers exert differential analgesic effects. It appears particularly interesting that R-flurbiprofen, for instance, which is not or only to a small extent inverted in humans and rats, is practically devoid of prostaglandin synthesis inhibition in vitro. Consequently, in line with current thinking, R-flurbiprofen is not toxic to the gastrointestinal tract and shows no anti-inflammatory effects. In contrast to current concepts, however, this enantiomer does exert analgesic activity in different models of pain and nociception. It is concluded that R-flurbiprofen and, possibly, other R-enantiomers of 2-arylpropionic acids may exert novel analgesic effects independently of peripheral prostaglandin synthesis inhibition in inflamed tissue.

  4. Enantiomer-specific toxicity and bioaccumulation of alpha-cypermethrin to earthworm Eisenia fetida.

    PubMed

    Diao, Jinling; Xu, Peng; Liu, Donghui; Lu, Yule; Zhou, Zhiqiang

    2011-09-15

    Alpha-cypermethrin, a synthetic pyrethroid, is highly effective against a wide range of chewing and sucking insects in crops, and it is a racemic mixture of two enantiomers ((+)-1R-cis-αS+(-)-1S-cis-αR). Studies about the toxicity of alpha-cypermethrin to non-target organisms are mainly focused on aquatic organisms, whereas information regarding terrestrial organisms is relatively much less. Very little report about its enantioselective toxicity is known, so the present study tested the enantiomer-specific acute toxicity to earthworm Eisenia fetida. Experiment about bioaccumulation of two enantiomers in soil was conducted, peak-shaped accumulation curves were observed for both enantiomers, and the calculated biota to soil accumulations factor (BSAF) have significant difference between the two enantiomers. It was obvious that earthworm can uptake alpha-cypermethrin enantioselectively, preferentially accumulating (-)-(1S-cis-αR)-enantiomer. Great difference in toxicity to earthworm between two enantiomers was found, and the calculated LC(50) values for (+)-(1R-cis-αS)-, (-)-(1S-cis-αR)-, and rac-alpha-cypermethrin were 49.53, 1663.87 and 165.61 ng/cm(2), respectively. The acute toxicity of alpha-cypermethrin enantiomers was enantioselective.

  5. Quantitative analysis of three chiral pesticide enantiomers by high-performance column liquid chromatography.

    PubMed

    Wang, Peng; Liu, Donghui; Gu, Xu; Jiang, Shuren; Zhou, Zhiqiang

    2008-01-01

    Methods for the enantiomeric quantitative determination of 3 chiral pesticides, paclobutrazol, myclobutanil, and uniconazole, and their residues in soil and water are reported. An effective chiral high-performance liquid chromatographic (HPLC)-UV method using an amylose-tris(3,5-dimethylphenylcarbamate; AD) column was developed for resolving the enantiomers and quantitative determination. The enantiomers were identified by a circular dichroism detector. Validation involved complete resolution of each of the 2 enantiomers, plus determination of linearity, precision, and limit of detection (LOD). The pesticide enantiomers were isolated by solvent extraction from soil and C18 solid-phase extraction from water. The 2 enantiomers of the 3 pesticides could be completely separated on the AD column using n-hexane isopropanol mobile phase. The linearity and precision results indicated that the method was reliable for the quantitative analysis of the enantiomers. LODs were 0.025, 0.05, and 0.05 mg/kg for each enantiomer of paclobutrazol, myclobutanil, and uniconazole, respectively. Recovery and precision data showed that the pretreatment procedures were satisfactory for enantiomer extraction and cleanup. This method can be used for optical purity determination of technical material and analysis of environmental residues.

  6. The impact of baseline faecal egg counts on the efficacy of single-dose albendazole against Trichuris trichiura.

    PubMed

    Levecke, B; Mekonnen, Z; Albonico, M; Vercruysse, J

    2012-02-01

    There is considerable variation in the efficacy of single-dose albendazole (400mg) against Trichuris trichiura across human trials. Factors contributing to this variation have not yet been identified. We assessed the impact of mean baseline faecal egg counts (FEC) on the efficacy of single-dose albendazole against T. trichiura in five previously conducted trials. Our results suggest that efficacy measured by reduction in mean FECs decreased significantly (p<0.0001) when mean baseline FECs increased, highlighting that this parameter should be considered as an important confounding factor for drug efficacy.

  7. Enantiomer resolution by using capillary zone electrophoresis: resolution of racemic tryptophan and determination of the enantiomer composition of commercial pharmaceutical epinephrine.

    PubMed

    Fanali, S; Bocek, P

    1990-09-01

    The enantiomers of D- and L-tryptophan were separated by capillary electrophoresis, using alpha-cyclodextrin as a chiral active component in the background electrolyte. The separation of (-) and (+) epinephrine was achieved by supplementing the background electrolyte with Heptakis (2,6-di-O-methyl-beta-cyclodextrin). As a practical application of the method, the quantitative analysis of (-) and (+) enantiomers in commercial pharmaceutical solutions of adrenaline is shown.

  8. A consideration of the patentability of enantiomers in the pharmaceutical industry in the United States.

    PubMed

    Miller, Chris P; Ullrich, John W

    2008-06-01

    During the last thirty years, concern over stereoselectivity of drug action has drawn a great deal of interest within the pharmaceutical field due to an improved understanding of the pharmacology and pharmacokinetics of enantiomers. Developing single enantiomers versus racemates or introducing a single enantiomer following the development of the racemic mixture appears to be the new trend. The intellectual property status of single enantiomers from racemates may be unclear. Drug discoverers and patent attorneys must examine the examples of the past to establish an appropriate pathway towards the development and intellectual property protection of chiral drugs. The review will focus on the patenting of an enantiomer in view of the prior art disclosure for the racemic mixture.

  9. Comparative Performances of Flubendazole and Albendazole in Cystic Echinococcosis: Ex Vivo Activity, Plasma/Cyst Disposition, and Efficacy in Infected Mice ▿

    PubMed Central

    Ceballos, Laura; Elissondo, Celina; Sánchez Bruni, Sergio; Denegri, Guillermo; Lanusse, Carlos; Alvarez, Luis

    2011-01-01

    The need to identify improved therapy against cystic echinococcosis (CE) has motivated pharmacology-based research. The comparative pharmacological performances of the benzimidazole compounds flubendazole (FLBZ) and albendazole (ABZ) were addressed here. The goals of the work were as follows: (i) to evaluate the ex vivo activities of FLBZ, ABZ, and their respective metabolites against Echinococcus granulosus protoscoleces, (ii) to compare the plasma and cyst disposition kinetics for the two drugs in infected mice, and (iii) to compare the clinical efficacies of FLBZ and ABZ against CE in mice. For the ex vivo study, E. granulosus protoscoleces were incubated with FLBZ, reduced FLBZ (R-FLBZ), ABZ, and ABZ-sulfoxide (ABZSO) (10 nmol/ml). Protoscolex viability was monitored by the methylene blue exclusion test and scanning electron microscopy (SEM). For the pharmacokinetic study, BALB/c mice with CE were allocated to two different groups and orally treated with either FLBZ or ABZ (5 mg/kg of body weight), both formulated as a cyclodextrin-based solution. Blood and cyst samples were taken up to 12 h posttreatment and analyzed by high-performance liquid chromatography (HPLC). For the efficacy study, CE-infected BALB/c mice were divided into three groups: the unmedicated control group and the FLBZ- and ABZ-treated groups. Oral treatments were performed twice a day during 25 days. After treatment, all animals were killed and the weight of the cysts was recorded. Loss of protoscolex viability was observed after drug incubation. FLBZ was detected in plasma (area under the concentration-versus-time curve [AUC] = 1.8 μg·h/ml) and cysts (AUC = 0.3 μg·h/g) collected from treated infected animals. Conversely, ABZSO was the only active molecule measured in plasma (AUC = 4.4 μg·h/ml) and cysts (AUC = 1.5 μg·h/g) after ABZ treatment. FLBZ induced a 90% reduction in cyst weight in comparison to those collected from untreated control mice (P < 0.05). However, no differences

  10. Human tyrosinase is able to oxidize both enantiomers of rhododendrol.

    PubMed

    Ito, Shosuke; Gerwat, Wolfram; Kolbe, Ludger; Yamashita, Toshiharu; Ojika, Makoto; Wakamatsu, Kazumasa

    2014-11-01

    Racemic RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol, RD) was used as a topical skin-whitening agent until it was recently reported to induce leukoderma. We then showed that oxidation of RD with mushroom tyrosinase rapidly produces RD-quinone, which is quickly converted to RD-cyclic quinone and RD-hydroxy-p-quinone. In this study, we examined whether either or both of the enantiomers of RD can be oxidized by human tyrosinase. Using a chiral HPLC column, racemic RD was resolved optically to R(-)-RD and S(+)-RD enantiomers. In the presence of a catalytic amount of l-dopa, human tyrosinase, which can oxidize l-tyrosine but not d-tyrosine, was found to oxidize both R(-)- and S(+)-RD to give RD-catechol and its oxidation products. S(+)-RD was more effectively oxidized than l-tyrosine, while R(-)-RD was less effective. These results support the notion that the melanocyte toxicity of RD depends on its tyrosinase-catalyzed conversion to toxic quinones and the concomitant production of reactive oxygen species.

  11. Photosensitized oxidation of aryl benzyl sulfoxides. Evidence for nucleophilic assistance to the C-s bond cleavage of aryl benzyl sulfoxide radical cations.

    PubMed

    Del Giacco, Tiziana; Lanzalunga, Osvaldo; Lapi, Andrea; Mazzonna, Marco; Mencarelli, Paolo

    2015-02-20

    The radical cations of a series of aryl benzyl sulfoxides (4-X-C6H4CH2SOC6H4Y(+•)) have been generated by photochemical oxidation of the parent sulfoxides sensitized by 3-cyano-N-methylquinolinium perchlorate (3-CN-NMQ(+)ClO4(-)). Steady-state photolysis experiments showed the prevailing formation of benzylic products deriving from the C-S fragmentation in the radical cations, together with sulfur-containing products. Formation of sulfoxide radical cations was unequivocally established by laser flash photolysis experiments showing the absorption bands of 3-CN-NMQ(•) (λmax = 390 nm) and of the radical cations (λmax = 500-620 nm). The decay rate constants of radical cations, determined by LFP experiments, decrease by increasing the electron-donating power of the arylsulfinyl Y substituent and to a smaller extent by increasing the electron-withdrawing power of the benzylic X substituent. A solvent nucleophilic assistance to the C-S bond cleavage has been suggested, supported by the comparison of substituent effects on the same process occurring in aryl tert-butyl sulfoxide radical cations. DFT calculations, performed to determine the bond dissociation free energy in the radical cations, the transition state energies associated with the unimolecular C-S bond cleavage, and the charge and spin delocalized on their structures, were also useful to endorse the nucleophilic assistance to the C-S scission.

  12. A new reliable method for dimethyl sulfoxide analysis in wastewater: dimethyl sulfoxide in Philadelphia's three water pollution control plants.

    PubMed

    Cheng, Xianhao; Peterkin, Earl

    2007-05-01

    A simple but reliable procedure was developed to analyze dimethyl sulfoxide (DMSO) in wastewater. The isotope DMSO_d6 was used as the internal standard to ensure accuracy. The DMSO was reduced with stannous chloride and measured as dimethyl sulfide (DMS) with purge-and-trap gas chromatography/mass spectrometry. The method detection limit was at the sub-microgram-per-milliliter level; precision, as measured by standard deviation, was better than +/- 0.5%; and the recoveries were between 95 and 105% at the level of 2 microg/mL. The procedure could use standard analytical instrumentation used for volatile organic compound analysis. A field study was conducted to validate the method and quantify DMSO concentration range in the three water pollution control plants (WPCPs) in the city of Philadelphia, Pennsylvania. Results showed that, when a local chemical facility discharged, DMSO concentration could be as high as 12 mg/L in the influent to a WPCP. This would lead to the formation of a toxic "canned corn" DMS odor during the treatment processes. PMID:17571849

  13. The anthelmintic efficacy of albendazole against gastrointestinal roundworms, tapeworms, lungworms and liverflukes in sheep.

    PubMed

    van Schalkwyk, P C; Geyser, T L; Récio, M; Erasmus, F P

    1979-03-01

    Anthelmintic trials were carried out to evaluate the efficacy of albendazole against helmi of 2,5 to 3,8 mg/kg administered orally, resulted in a 98,8 to 100% reduction of adult parasites of the genera Haemonchus, Ostertagia, Trichostrongylus, Nematodirus, Gaigeria, Oesophagostomum, Chabertia, Marshallagia and Cooperia. Against the immature stages of these genera, except for Marshallagia and Cooperia, which were not tested, a dose level of 2,5 to 3,8 mg/kg was 83,9-100% effective. Albendazole at 2,5 mg/kg was 99,0% effective against adult stages of Dictyocaulus; its activity at a dose of 3,8 mg/kg against the immature stages of D. filaria was 89,3%. In sheep naturally infested with Moniezia, 100% elimination was obtained at a dose level of 2,5 mg/kg. Dose levels of 3,8 mg/kg and higher were more than 76% effective against adult Fasciola hepatica, while a dose of 4,8 mg/kg was 63% effective against adult Fasciola gigantica.

  14. The anthelmintic efficacy of albendazole against gastrointestinal roundworms, tapeworms, lungworms and liverflukes in sheep.

    PubMed

    van Schalkwyk, P C; Geyser, T L; Récio, M; Erasmus, F P

    1979-03-01

    Anthelmintic trials were carried out to evaluate the efficacy of albendazole against helmi of 2,5 to 3,8 mg/kg administered orally, resulted in a 98,8 to 100% reduction of adult parasites of the genera Haemonchus, Ostertagia, Trichostrongylus, Nematodirus, Gaigeria, Oesophagostomum, Chabertia, Marshallagia and Cooperia. Against the immature stages of these genera, except for Marshallagia and Cooperia, which were not tested, a dose level of 2,5 to 3,8 mg/kg was 83,9-100% effective. Albendazole at 2,5 mg/kg was 99,0% effective against adult stages of Dictyocaulus; its activity at a dose of 3,8 mg/kg against the immature stages of D. filaria was 89,3%. In sheep naturally infested with Moniezia, 100% elimination was obtained at a dose level of 2,5 mg/kg. Dose levels of 3,8 mg/kg and higher were more than 76% effective against adult Fasciola hepatica, while a dose of 4,8 mg/kg was 63% effective against adult Fasciola gigantica. PMID:551183

  15. Mansonella perstans: safety and efficacy of ivermectin alone, albendazole alone and the two drugs in combination.

    PubMed

    Asio, S M; Simonsen, P E; Onapa, A W

    2009-01-01

    The safety and efficacy of a single dose of ivermectin alone (150-200 microg/kg bodyweight), albendazole alone (400 mg) or the combination of these two drugs was assessed, in Uganda, in three groups of individuals infected with Mansonella perstans (with 15, 13 and 15 subjects in each group, respectively). No side-effects were observed or reported during the first 7 days post-treatment and every subject remained microfilaraemic during the 12 months of follow-up. In the subjects given ivermectin alone or albendazole alone, the microfilarial intensities consistently remained close to their pre-treatment levels. In the subjects given both drugs, however, the microfilarial intensities decreased slightly after treatment and at 1 and 3 months post-treatment (but not at 6, 9 or 12 months) they were significantly lower than in the two other groups combined. The three single-dose drug regimens investigated were thus well tolerated but had disappointingly low efficacies in the treatment of M. perstans microfilaraemias. PMID:19173774

  16. Evaluation of albendazole, pyrantel, bephenium, pyrantel-praziquantel and pyrantel-bephenium for single-dose mass treatment of necatoriasis.

    PubMed

    Nahmias, J; Kennet, R; Goldsmith, R; Greenberg, Z

    1989-12-01

    An effective drug for single-dose mass treatment of necatoriasis was sought by testing three drugs and two drug combinations in Ethiopian immigrants to Israel found to have light infections. The drugs tested sequentially in single-doses were pyrantel pamoate (20 mg kg-1, 81 subjects); bephenium hydroxynaphthoate (2.5-5 g, 65 subjects); combined pyrantel and bephenium (25 subjects); combined pyrantel (20 mg kg-1) and praziquantel (40 mg kg-1) (16 subjects); and albendazole (400 mg, 77 subjects). Follow-up under conditions without likelihood of reinfection was by one stool examination. Cure rates with albendazole, pyrantel-bephenium and pyrantel-praziquantel were 84, 80 and 81% respectively; these rates were significantly higher than the 49% found for bephenium and the 51% for pyrantel (P less than 0.05). Egg reductions in those not cured were pyrantel (22%), bephenium (6%), pyrantel-bephenium (34%), pyrantel-praziquantel (3%) and albendazole (6%). Albendazole was the most promising single drug treatment; unexpected was the high effectiveness of pyrantel-praziquantel in combination. PMID:2619378

  17. Probing the stereochemistry of successive sulfoxidation of the insecticide fenamiphos in soils.

    PubMed

    Cai, Xiyun; Xiong, Weina; Xia, Tingting; Chen, Jingwen

    2014-10-01

    Successive sulfoxidation is widely recognized as a general characteristic of the metabolism of chiral or prochiral thioethers, producing sulfoxides, and sulfones. However, information related to the stereochemistry of this process in soils is rare. In this study, the biotic transformation of the insecticide fenamiphos (a model thioether) was followed over two months in three soils, through separate incubations with fenamiphos parent, the sulfoxide intermediate (FSO), the sulfone intermediate (FSO2), and their respective stereoisomers. The results showed that the successive sulfoxidation involved oxidation of fenamiphos to FSO and subsequently to FSO2 as well as diastereomerization/enantiomerization of FSO, all of which were primarily biotic and stereoselective. The concomitant hydrolysis of fenamiphos, FSO, and FSO2 to phenols that occurred at lower rates was biotically favorable, but not stereoselective. The stereochemistry of this successive sulfoxidation transferred principally through two parallel systems, R(+)-fenamiphos → SRPR(+)-/SSPR(-)-FSO → R(+)-FSO2 and S(-)-fenamiphos → SRPS(+)-/SSPS(-)-FSO → S(-)-FSO2, between which unidirectional intersystem crossing occurred at FSO via isomeric conversions and created a system of S(-)-fenamiphos → SRPR(+)-/SSPR(-)-FSO → R(+)-FSO2. This pattern accounts for the enrichment of the intermediates SSPR(-)-/SSPS(-)-FSO and R(+)-FSO2 that are toxicologically close to the highly toxic S(-)-fenamiphos, associated with soil application of fenamiphos. Selective formation/depletion of these intermediate stereoisomers leads to dramatic variations in the ecotoxicological effects of the thioether insecticide.

  18. Pharmacokinetics of the individual enantiomers of vigabatrin in neonates with uncontrolled seizures

    PubMed Central

    VAUZELLE-KERVROËDAN, F.; REY, E.; PONS, G.; d'ATHIS, Ph.; CHIRON, C.; DULAC, O.; DUMAS, C.; OLIVE, G.

    1996-01-01

    The antiepileptic drug vigabatrin (VGB) is a selective irreversible inhibitor of GABA-transaminase. It is administered as a racemic R(−), S(+) mixture, but the pharmacological activity of vigabatrin resides in the S(+) enantiomer and the R(−) enantiomer is inactive. The pharmacokinetic parameters of the two enantiomers have been studied after administration of a single oral 125 mg dose of the racemate to six neonates. The mean values of Cmax and AUC of the S(+) enantiomer were significantly lower (Cmax : 14.0±4.3 mg l−1; AUC: 143±44 mg l−1 h) than those of the R(−) enantiomer (Cmax: 34.1±9.5 mg l−1; AUC: 231±88 mg l−1 h), whereas no significant difference in the time to reach Cmax (S(+): 2.1±1.1 h; R(−): 2.2±1 h) was observed between the two enantiomers. During chronic administration (125 mg twice daily over 4 days), there was no evidence of accumulation of either enantiomer. PMID:8971436

  19. Differentiation of antiinflammatory and antitumorigenic properties of stabilized enantiomers of thalidomide analogs.

    PubMed

    Jacques, Vincent; Czarnik, Anthony W; Judge, Thomas M; Van der Ploeg, Lex H T; DeWitt, Sheila H

    2015-03-24

    Therapeutics developed and sold as racemates can exhibit a limited therapeutic index because of side effects resulting from the undesired enantiomer (distomer) and/or its metabolites, which at times, forces researchers to abandon valuable scaffolds. Therefore, most chiral drugs are developed as single enantiomers. Unfortunately, the development of some chirally pure drug molecules is hampered by rapid in vivo racemization. The class of compounds known as immunomodulatory drugs derived from thalidomide is developed and sold as racemates because of racemization at the chiral center of the 3-aminoglutarimide moiety. Herein, we show that replacement of the exchangeable hydrogen at the chiral center with deuterium allows the stabilization and testing of individual enantiomers for two thalidomide analogs, including CC-122, a compound currently in human clinical trials for hematological cancers and solid tumors. Using "deuterium-enabled chiral switching" (DECS), in vitro antiinflammatory differences of up to 20-fold are observed between the deuterium-stabilized enantiomers. In vivo, the exposure is dramatically increased for each enantiomer while they retain similar pharmacokinetics. Furthermore, the single deuterated enantiomers related to CC-122 exhibit profoundly different in vivo responses in an NCI-H929 myeloma xenograft model. The (-)-deuterated enantiomer is antitumorigenic, whereas the (+)-deuterated enantiomer has little to no effect on tumor growth. The ability to stabilize and differentiate enantiomers by DECS opens up a vast window of opportunity to characterize the class effects of thalidomide analogs and improve on the therapeutic promise of other racemic compounds, including the development of safer therapeutics and the discovery of new mechanisms and clinical applications for existing therapeutics.

  20. Differentiation of antiinflammatory and antitumorigenic properties of stabilized enantiomers of thalidomide analogs.

    PubMed

    Jacques, Vincent; Czarnik, Anthony W; Judge, Thomas M; Van der Ploeg, Lex H T; DeWitt, Sheila H

    2015-03-24

    Therapeutics developed and sold as racemates can exhibit a limited therapeutic index because of side effects resulting from the undesired enantiomer (distomer) and/or its metabolites, which at times, forces researchers to abandon valuable scaffolds. Therefore, most chiral drugs are developed as single enantiomers. Unfortunately, the development of some chirally pure drug molecules is hampered by rapid in vivo racemization. The class of compounds known as immunomodulatory drugs derived from thalidomide is developed and sold as racemates because of racemization at the chiral center of the 3-aminoglutarimide moiety. Herein, we show that replacement of the exchangeable hydrogen at the chiral center with deuterium allows the stabilization and testing of individual enantiomers for two thalidomide analogs, including CC-122, a compound currently in human clinical trials for hematological cancers and solid tumors. Using "deuterium-enabled chiral switching" (DECS), in vitro antiinflammatory differences of up to 20-fold are observed between the deuterium-stabilized enantiomers. In vivo, the exposure is dramatically increased for each enantiomer while they retain similar pharmacokinetics. Furthermore, the single deuterated enantiomers related to CC-122 exhibit profoundly different in vivo responses in an NCI-H929 myeloma xenograft model. The (-)-deuterated enantiomer is antitumorigenic, whereas the (+)-deuterated enantiomer has little to no effect on tumor growth. The ability to stabilize and differentiate enantiomers by DECS opens up a vast window of opportunity to characterize the class effects of thalidomide analogs and improve on the therapeutic promise of other racemic compounds, including the development of safer therapeutics and the discovery of new mechanisms and clinical applications for existing therapeutics. PMID:25775521

  1. Enantioselective HPLC determination and pharmacokinetic study of secnidazole enantiomers in rats.

    PubMed

    Du, Jiangbo; Zhang, Yifan; Chen, Yao; Liu, Dongqin; Chen, Xiaoyan; Zhong, Dafang

    2014-08-15

    Secnidazole is a long-lasting nitroimidazole antimicrobial agent that is used as racemic mixture in clinical settings. We developed and validated an enantioselective high-performance liquid chromatography method to determine secnidazole enantiomers in rat plasma. Secnidazole enantiomers and S-(-)-ornidazole (internal standard) were extracted from 50 μL of rat plasma using diethyl ether-dichloromethane (3:2, v/v). Baseline resolution (Rs=2.45) was achieved within 7.0 min on a Chiral-AGP column (150 mm × 4.0mm, 5 μm) at 20°C. The mobile phase consisted of 10mM ammonium acetate-methanol (96:4, v/v) and was delivered at a flow rate of 0.5 mL/min with ultraviolet detection at 318 nm. The method was linear over the concentration range 0.500-100 μg/mL for both enantiomers. The lower limit of quantification was 0.500 μg/mL for both enantiomers. The relative standard deviation values for intra- and inter-day precision were 0.8-8.6 and 1.8-8.2% for S-(+)-secnidazole and R-(-)-secnidazole, respectively. The relative error values of accuracy ranged from -7.8 to 1.1% for S-(+)-secnidazole and from -7.3 to -0.1% for R-(-)-secnidazole. The method was successfully used to determine the pharmacokinetic properties of secnidazole enantiomers in rats after administration of the racemate and individual enantiomers. The pharmacokinetic results indicate that the disposition of secnidazole enantiomers is not stereoselective and chiral inversion and enantiomer-enantiomer interaction do not occur in rats. PMID:25049211

  2. Phenylalanine-based polyarylacetylenes as enantiomer-differentiating alignment media.

    PubMed

    Krupp, Alexis; Reggelin, Michael

    2012-12-01

    Lyotropic liquid crystalline phases of a phenylalanine-based polyacetylene are introduced as new enantiodifferentiating alignment media. Based on the unusual temperature dependence of the quadrupolar splitting of the (2)H-signal of the solvent (CDCl(3)), three distinct states of the phase with different orientational properties can be identified. This offers the opportunity to measure multiple alignment data sets without changing the sample. Unexpectedly, the largest difference in the orientation of the enantiomers of isopinocampheol was found in the high temperature domain of the phase. This is even more astonishing because the helical structure of the polymer backbone seems to break down at temperatures above approximately 10 °C, leaving the stereogenic centers of the amino acid moieties in the repeating units as the only reason for the enantiodifferentiation.

  3. Efficacy of albendazole against nematode parasites isolated from a goat farm in Ethiopia: relationship between dose and efficacy in goats.

    PubMed

    Eguale, Tadesse; Chaka, Hassen; Gizaw, Daniel

    2009-10-01

    A suspected case of albendazole resistance in a goat farm of Hawassa University was examined using faecal egg count reduction test (FECRT), controlled anthelmintic efficacy test and egg hatch assay (EHA) to verify the development of resistance and/or the need for higher doses of the drug in goats than in sheep. The experiment was conducted in 12 sheep (2 groups: treatment versus control) and 24 goats (4 groups: 3 treatments versus control, n = 6; per group) following artificial infection with infective larvae of Haemonchus contortus and Oesophagostomum columbianum. The first group of sheep and goats were treated orally with albendazole at the dose rate of 3.8 mg/kg body weight (i.e. manufacturer's recommended dose for sheep) while the second group of sheep and the fourth group of goats were left untreated. The second and the third group of goats were treated with albendazole at 5.7 and 7.6 mg/kg respectively. The FECRT showed an efficacy of albendazole in goats to be 65.5, 81.4 and 84.1% at the dose rate of 3.8, 5.7 and 7.6 mg/kg body weight respectively while in sheep it was 62% at the dose rate of 3.8 mg/kg. Increasing the dose to 1.5 the sheep recommended dose induced minor improvement of efficacy in goats; however the efficacy was almost the same at 1.5 and twice the dose recommended for sheep. Worm counts at day 15 post-treatment revealed that H. contortus has developed resistance to albendazole. EHA results also supported these findings. On the other hand, O. columbianum was 100% susceptible at all dose levels tested.

  4. In vitro and in vivo effects of 2-methoxyestradiol, either alone or combined with albendazole, against Echinococcus metacestodes.

    PubMed

    Spicher, Martin; Naguleswaran, Arunasalam; Ortega-Mora, Luis M; Müller, Joachim; Gottstein, Bruno; Hemphill, Andrew

    2008-08-01

    The metacestode (larval) stage of the tapeworm Echinococcus multilocularis causes alveolar echinococcosis (AE), a mainly hepatic disease characterized by continuous asexual proliferation of metacestodes by exogenous budding, resulting in the tumor-like, infiltrative growth of the parasite lesion. Current chemotherapeutical treatment of AE relies on the use of benzimidazoles (albendazole, mebendazole), but these drugs act parasitostatic rather than parasitocidal, and in case of side effects such as liver toxicity, patients are left without valuable alternatives. 2-ME2 is a natural metabolite of estradiol, with a documented anti-angiogenic and broad spectrum anti-tumour activity. Treatments of in vitro cultured E. multilocularis metacestodes with 2-ME2 (2-10 microM) showed that the drug has an adverse effect on parasite viability. First, 2-ME in vitro treatment downscaled the transcription of the 14-3-3-pro-tumorogenic zeta-isoform in E. multilocularis metacestodes. Second, scanning and transmission electron microscopy showed that the germinal layer of E. multilocularis metacestodes was dramatically damaged following 2-ME2-treatment, and the effect was dose-dependent. Similar results were obtained with E. granulosus metacestodes. Bioassays were performed in mice injected with 2-ME2-treated and albendazole-treated metacestodes, or parasites-treated with both 2-ME and albendazole in combination. These assays indicated that, despite inducing considerable damage in vitro, neither of the drugs was capable of exerting a true parasiticidal effect, but best results were achieved with a combination of both compounds. In vivo treatment in E. multilocularis-infected mice for a period of 6 weeks showed that a combined 2-ME2/albendazole based treatment lead to a reduction in parasite weight, but the results did not show statistical difference from the application of albendazole alone.

  5. Therapeutic effects of Sophora moorcroftiana alkaloids in combination with albendazole in mice experimentally infected with protoscolices of Echinococcus granulosus.

    PubMed

    Ma, X M; Bao, G Sh; Wan, J M; Liao, D J; Yin, Sh F; Meng, X Q; Zhou, G K; Lu, X M; Li, H Y

    2007-10-01

    The objective of the present study was to determine if the combination of alkaloids from Sophora moorcroftiana seeds and albendazole might be effective in the treatment of experimental echinococcosisin female NIH mice (6 weeks old and weighing 18-20 g, N = 8 in each group) infected withprotoscolices of Echinococcus granulosus. Viable protoscolices (N = 6 x 10(3)) were cultured in vitro in 1640 medium and mortality was calculated daily. To determine the in vivo efficacy, mice were inoculated intraperitoneally with viable protoscolices and then treated once daily by gavage for three months with the alkaloids (50 mg kg-1 day-1) and albendazole (50 mg kg-1 day-1), separately and in combination (both alkaloids at 25 mg kg-1 day-1 and albendazole at 25 mg kg-1 day-1). Next, the hydatid cysts collected from the peritoneal cavity of the animals were weighed and serum IL-4, IL-2, and IgE levels were analyzed. Administration of alkaloids to cultured protoscolices showed significant dose- and time-dependent killing effects. The weight of hydatid cysts was significantly decreased upon treatment with each drug (P < 0.01), but the decrease was more prominent and the rate of hydatid cyst growth inhibition was much higher (76.1%) in the group receiving the combined treatments (18.3 +/- 4.6 mg). IL-4 and total IgE were decreased (939 +/- 447 pg/mL and 2.03 +/- 0.42 IU/mL, respectively) in serum from mice treated with alkaloids and albendazole compared with the untreated control (1481 +/- 619 pg/mL and 3.31 +/- 0.37 IU/mL; P < 0.01). These results indicate that S. moorcroftiana alkaloids have protoscolicidal effects and the combination of alkaloids and albendazole has significant additive effects.

  6. Separation of Betti Reaction Product Enantiomers: Absolute Configuration and Inhibition of Botulinum Neurotoxin A

    PubMed Central

    2011-01-01

    The racemic product of the Betti reaction of 5-chloro-8-hydroxyquinoline, benzaldehyde, and 2-aminopyridine was separated by chiral HPLC to determine which enantiomer inhibited botulinum neurotoxin serotype A. When the enantiomers unexpectedly proved to have comparable activity, the absolute structures of (+)-(R)-1 and (−)-(S)-1 were determined by comparison of calculated and observed circular dichroism spectra. Molecular modeling studies were undertaken in an effort to understand the observed bioactivity and revealed different ensembles of binding modes, with roughly equal binding energies, for the two enantiomers. PMID:22102940

  7. [Racemation of the benzodiazepines camazepam and ketazolam and receptor binding of enantiomers].

    PubMed

    Blaschke, G; Kley, H; Müller, W E

    1986-06-01

    The chiral benzodiazepines camazepam (1) and ketazolam (2) were resolved into the enantiomers by chromatography on the optically active adsorbent poly[(S)-N-(1-cyclohexylethyl)-methacrylamide] and fractional crystallisation or repeated chromatography, respectively. The IC50 values of the isomers and of the racemates of both compounds were determined by displacement of radioactively labelled 3H-flunitrazepam and 3H-propyl-beta-carboline-carboxylate from their specific binding sites. (+)-Camazepam exhibits 14fold higher affinity compared to the (-)-enantiomer. In contrast only slight differences in the receptor affinity are observed with the ketazolam enantiomers.

  8. Characterization of Lassa Virus Cell Entry Inhibitors: Determination of the Active Enantiomer by Asymmetric Synthesis

    PubMed Central

    Whitby, Landon R.; Lee, Andrew M.; Kunz, Stefan; Oldstone, Michael B. A.; Boger, Dale L.

    2009-01-01

    The comparative characterization of a series of 4-acyl-1,6-dialkylpiperazin-2-ones as potent cell entry inhibitors of the hemorrhagic fever arenavirus Lassa (LASV) is disclosed. The resolution and examination of the individual enantiomers of the prototypical LASV cell entry inhibitor 3 (16G8) is reported and the more potent (–)-enantiomer was found to be 15-fold more active than the corresponding (+)-enantiomer. The absolute configuration of (–)-3 was established by asymmetric synthesis of the active inhibitor (–)-(S)-3 (lassamycin-1). A limited deletion scan of lassamycin-1 defined key structural features required of the prototypical inhibitors. PMID:19428249

  9. Selective preparation of enantiomers by laser pulses: quantum model simulation for H 2POSH

    NASA Astrophysics Data System (ADS)

    Fujimura, Y.; González, L.; Hoki, K.; Manz, J.; Ohtsuki, Y.

    1999-06-01

    This Letter presents the first quantum model simulation of the selective preparation of enantiomers by means of optimal, elliptically polarized, infrared picosecond laser pulses. The laser-driven molecular dynamics is demonstrated by the time evolution of the representative wavepacket, from the initial state which corresponds to a 50:50% racemate of two equivalent enantiomers with opposite chiralities towards the nearly 100:0% preparation of a single enantiomer. The wavepacket dynamics is based on the quantum ab initio potential energy surface and dipole functions for the torsional vibration of the hydrogen atom around the P-S molecular axis of the model system H 2POSH.

  10. (S)-N-Methyldihydroquinazolinones are the Active Enantiomers of Retro-2 Derived Compounds against Toxins

    PubMed Central

    2013-01-01

    This study reports the synthesis, chromatographic separation, and pharmacological evaluation of the two enantiomers of a new compound, named Retro-2.1, active against toxins by inhibiting intracellular trafficking via the retrograde route. The absolute configuration of the bioactive enantiomer has been assigned from X-ray diffraction to the (S)-enantiomer. To date, (S)-Retro-2.1 is the most potent molecule to counteract the cytotoxic potential of ricin and Shiga toxin, with EC50 values of 23 and 54 nM, respectively. PMID:24900779

  11. Thymosin β4-sulfoxide attenuates inflammatory cell infiltration and promotes cardiac wound healing.

    PubMed

    Evans, Mark A; Smart, Nicola; Dubé, Karina N; Bollini, Sveva; Clark, James E; Evans, Hayley G; Taams, Leonie S; Richardson, Rebecca; Lévesque, Mathieu; Martin, Paul; Mills, Kevin; Riegler, Johannes; Price, Anthony N; Lythgoe, Mark F; Riley, Paul R

    2013-01-01

    The downstream consequences of inflammation in the adult mammalian heart are formation of a non-functional scar, pathological remodelling and heart failure. In zebrafish, hydrogen peroxide released from a wound is the initial instructive chemotactic cue for the infiltration of inflammatory cells, however, the identity of a subsequent resolution signal(s), to attenuate chronic inflammation, remains unknown. Here we reveal that thymosin β4-sulfoxide lies downstream of hydrogen peroxide in the wounded fish and triggers depletion of inflammatory macrophages at the injury site. This function is conserved in the mouse and observed after cardiac injury, where it promotes wound healing and reduced scarring. In human T-cell/CD14+ monocyte co-cultures, thymosin β4-sulfoxide inhibits interferon-γ, and increases monocyte dispersal and cell death, likely by stimulating superoxide production. Thus, thymosin β4-sulfoxide is a putative target for therapeutic modulation of the immune response, resolution of fibrosis and cardiac repair. PMID:23820300

  12. The CGC enantiomer separation of 2-arylcarboxylic acid esters by using β-cyclodextrin derivatives as chiral stationary phases.

    PubMed

    Shi, Xueyan; Liu, Feipeng; Mao, Jianyou

    2016-03-17

    Chiral 2-arylcarboxylic acid esters are important intermediates in preparation of enantioenriched 2-arylpropionic acids type Non-steroidal anti-inflammatory drugs (NSAIDs). Enantiomer separation of 2-arylcarboxylic acid esters is crucial for evaluation of the asymmetric synthesis efficiency and the enantiomer excess of chiral 2-arylcarboxylic acid derivatives. The capillary gas chromatography (CGC) enantiomer separation of 17 pairs of 2-arylcarboxylic acid esters enantiomers was conducted by using seven different β-cyclodextrin derivatives (CDs) as chiral stationary phases. It was found that for the 7 pairs of 2-phenylpropionates enantiomers, CDs with both alkyl and acyl substituents especially 2,6-di-O-pentyl-3-O-butyryl-β-cyclodextrin exhibited better enantiomer separation abilities than the other CDs examined. For the 7 pairs of 2-(4-substituted phenyl)propionates enantiomers, 2,3,6-tri-O-methyl-β-cyclodextrin possessed better enantiomer separation abilities than the other CDs. Among the 3 pairs of 2-phenylbutyrates enantiomers examined, only methyl 2-phenylbutyrate enantiomers could be separated by three CDs among the 7 CDs tested, while enantiomers of ethyl 2-phenylbutyrate and isopropyl 2-phenylbutyrate couldn't be separated by any of the 7 CDs tested. Besides the structures of CDs, the structures of 2-arylcarboxylic acid esters including different ester moieties, substituents of phenyl, and different carboxylic acids moieties in 2-arylcarboxylic acid esters also affected the enantiomer separation results greatly. The CGC enantiomer separation results of 2-arylcarboxylic acid esters on different CDs are useful for solving the enantiomer separation problem of 2-arylcarboxylic acid esters. PMID:26920785

  13. Plasma disposition and faecal excretion of oxfendazole, fenbendazole and albendazole following oral administration to donkeys.

    PubMed

    Gokbulut, Cengiz; Akar, Ferda; McKellar, Quintin A

    2006-07-01

    Fenbendazole (FBZ), oxfendazole (fenbendazole sulphoxide, FBZSO), and albendazole (ABZ) were administered orally to donkeys at 10mg/kg bodyweight. Blood and faecal samples were collected from 1 to 120 h post-treatment. The plasma and faecal samples were analysed by high performance liquid chromatography (HPLC). The parent molecule and its sulphoxide and sulphone (FBZSO(2)) metabolites did not reach detectable concentrations in any plasma samples following FBZ administration. ABZ was also not detected in any plasma samples, but its sulphoxide and sulphone metabolites were detected, demonstrating that ABZ was completely metabolised by first-pass mechanisms in donkeys. Maximum plasma concentrations (C(max)) of FBZSO (0.49microg/mL) and FBZSO(2) (0.60microg/mL) were detected at (t(max)) 5.67 and 8.00h, respectively, following administration of FBZSO. The area under the curve (AUC) of the sulphone metabolite (10.33microg h/mL) was significantly higher than that of the parent drug FBZSO (5.17microg h/mL). C(max) of albendazole sulphoxide (ABZSO) (0.08g/mL) and albendazole sulphone (ABZSO(2)) (0.04microg/mL) were obtained at 5.71 and 8.00h, respectively, following ABZ administration. The AUC of the sulphoxide metabolite (0.84microg h/mL) of ABZ was significantly higher than that of the sulphone metabolite (0.50microg h/mL). The highest dry-faecal concentrations of parent molecules were detected at 32, 34 and 30h for FBZSO, FBZ and ABZ, respectively. The sulphide metabolite was significantly higher than the parent molecule after FBZSO administration. The parent molecule was predominant in the faecal samples following FBZ administration. After ABZ administration, the parent molecule was significantly metabolised, probably by gastrointestinal microflora, to its sulphoxide metabolite (ABZSO) that showed a similar excretion profile to the parent molecule in the faecal samples. The AUC of the parent FBZ was significantly higher than that of FBZSO and ABZ in faeces. It is

  14. Synthesis and spectroscopic behavior of highly luminescent Eu 3+-dibenzoylmethanate (DBM) complexes with sulfoxide ligands

    NASA Astrophysics Data System (ADS)

    Niyama, E.; Brito, H. F.; Cremona, M.; Teotonio, E. E. S.; Reyes, R.; Brito, G. E. S.; Felinto, M. C. F. C.

    2005-09-01

    In this paper the synthesis, characterization and photoluminescent behavior of the [RE(DBM) 3L 2] complexes (RE = Gd and Eu) with a variety of sulfoxide ligands; L = benzyl sulfoxide (DBSO), methyl sulfoxide (DMSO), phenyl sulfoxide (DPSO) and p-tolyl sulfoxide (PTSO) have been investigated in solid state. The emission spectra of the Eu 3+-β-diketonate complexes show characteristics narrow bands arising from the 5D 0 → 7F J ( J = 0-4) transitions, which are split according to the selection rule for C n, C nv or C s site symmetries. The experimental Judd-Ofelt intensity parameters ( Ω2 and Ω4), radiative ( Arad) and non-radiative ( Anrad) decay rates, and R02 for the europium complexes have been determined and compared. The highest value of Ω2 (61.9 × 10 -20 cm 2) was obtained to the complex with PTSO ligand, indicating that Eu 3+ ion is in the highly polarizable chemical environment. The higher values of the experimental quantum yield ( q) and emission quantum efficiency of the emitter 5D 0 level ( η) for the Eu-complexes with DMSO, DBSO and PTSO sulfoxides suggest that these complexes are promising Light Conversion Molecular Devices (LCMDs). The lower value of quantum yield ( q = 1%), for the hydrated complex [Eu(DBM) 3(H 2O)], indicates that the luminescence quenching occurs via multiphonon relaxation by coupling with the OH-oscillators from water molecule coordinated to rare earth ion. The pure red emission of the Eu-complexes has been confirmed by ( x, y) color coordinates.

  15. Synthesis and spectroscopic behavior of highly luminescent Eu(3+)-dibenzoylmethanate (DBM) complexes with sulfoxide ligands.

    PubMed

    Niyama, E; Brito, H F; Cremona, M; Teotonio, E E S; Reyes, R; Brito, G E S; Felinto, M C F C

    2005-09-01

    In this paper the synthesis, characterization and photoluminescent behavior of the [RE(DBM)3L2] complexes (RE=Gd and Eu) with a variety of sulfoxide ligands; L=benzyl sulfoxide (DBSO), methyl sulfoxide (DMSO), phenyl sulfoxide (DPSO) and p-tolyl sulfoxide (PTSO) have been investigated in solid state. The emission spectra of the Eu(3+)-beta-diketonate complexes show characteristics narrow bands arising from the 5D0-->7F(J) (J=0-4) transitions, which are split according to the selection rule for C(n), C(nv) or C(s) site symmetries. The experimental Judd-Ofelt intensity parameters (Omega2 and Omega4), radiative (A(rad)) and non-radiative (A(nrad)) decay rates, and R02 for the europium complexes have been determined and compared. The highest value of Omega2 (61.9x10(-20)cm2) was obtained to the complex with PTSO ligand, indicating that Eu3+ ion is in the highly polarizable chemical environment. The higher values of the experimental quantum yield (q) and emission quantum efficiency of the emitter 5D0 level (eta) for the Eu-complexes with DMSO, DBSO and PTSO sulfoxides suggest that these complexes are promising Light Conversion Molecular Devices (LCMDs). The lower value of quantum yield (q=1%), for the hydrated complex [Eu(DBM)3H2O], indicates that the luminescence quenching occurs via multiphonon relaxation by coupling with the OH-oscillators from water molecule coordinated to rare earth ion. The pure red emission of the Eu-complexes has been confirmed by (x, y) color coordinates.

  16. An efficient asymmetric synthesis of an estrogen receptor modulator by sulfoxide-directed borane reduction.

    PubMed

    Song, Zhiguo J; King, Anthony O; Waters, Marjorie S; Lang, Fengrui; Zewge, Daniel; Bio, Matthew; Leazer, Johnnie L; Javadi, Gary; Kassim, Amude; Tschaen, David M; Reamer, Robert A; Rosner, Thorsten; Chilenski, Jennifer R; Mathre, David J; Volante, R P; Tillyer, Richard

    2004-04-20

    An efficient asymmetric synthesis of a selective estrogen receptor modulator (SERM) that has a dihydrobenzoxathiin core structure bearing two stereogenic centers is reported. The stereogenic centers were established by an unprecedented chiral sulfoxide-directed stereospecific reduction of an alpha,beta-unsaturated sulfoxide to the saturated sulfide in one step. Studies to elucidate the mechanism for this reduction are reported. Highly efficient Cu(I)-mediated ether formation was used to install the ether side chain, and selective debenzylation conditions were developed to remove the benzyl protecting groups on the phenols.

  17. N.m.r. studies of the conformation of analogues of methyl beta-lactoside in methyl sulfoxide-d6.

    PubMed

    Rivera-Sagredo, A; Jiménez-Barbero, J; Martín-Lomas, M

    1991-12-16

    The 1H- and 13C-n.m.r. spectra of solutions of methyl beta-lactoside (1), all of its monodeoxy derivatives (2, 3, 6-10), the 3-O-methyl derivative (4), and methyl 4-O-beta-D-galactopyranosyl-D-xylopyranoside (5) in methyl sulfoxide-d6 have been analysed. The n.O.e.'s and specific desheildings indicate similar distributions of low-energy conformers, comparable to those in aqueous solution. The major conformer has torsion angles phi H and psi H of 49 degrees and 5 degrees, respectively, with contributions of conformers with phi/psi 24 degrees/-59 degrees, 22 degrees/32 degrees, and 6 degrees/44 degrees. PMID:1816924

  18. Self-dispersible nanocrystals of albendazole produced by high pressure homogenization and spray-drying.

    PubMed

    Paredes, Alejandro Javier; Llabot, Juan Manuel; Sánchez Bruni, Sergio; Allemandi, Daniel; Palma, Santiago Daniel

    2016-10-01

    Albendazole (ABZ) is a broad-spectrum antiparasitic drug used in the treatment of human or animal infections. Although ABZ has shown a high efficacy for repeated doses in monogastric mammals, its low aqueous solubility leads to erratic bioavailability. The aim of this work was to optimize a procedure in order to obtain ABZ self-dispersible nanocrystals (SDNC) by combining high pressure homogenization (HPH) and spray-drying (SD). The material thus obtained was characterized and the variables affecting both the HPH and SD processes were studied. As expected, the homogenizing pressure and number of cycles influenced the final particle size, while the stabilizer concentration had a strong impact on SD output and redispersion of powders upon contact with water. ABZ SDNC were successfully obtained with high process yield and redispersibility. The characteristic peaks of ABZ were clearly identified in the X-ray patterns of the processed samples. A noticeable increase in the dissolution rate was observed in the aqueous environment.

  19. Effect of a controlled-release albendazole capsule on parasitism and productivity of sheep.

    PubMed

    Corba, J; Krupicer, I; Legény, J; Juris, P; Veselý, L

    1991-11-01

    The efficacy of intraruminal albendazole (ABZ) capsules (Profitril-Captec) and the effect of treatment on productivity were studied in 300 ewes infected with gastrointestinal nematodes and the trematode Dicrocoelium dendriticum. Coprological tests revealed that treated animals remained negative for 10 weeks after the administration of capsules. Contamination of pasture with nematode larvae was significantly reduced during the whole experiment. Necropsy of 14 animals (seven treated and seven untreated) showed 96.9-99.2% efficacy against the nematodes Nematodirus spp., Oesophagostomum spp., Cooperia spp., Trichostrongylus spp. and Trichuris ovis, while efficacy was 88.5% against D. dendriticum. During the 6 month pasture season (May-October 1989), treated ewes produced on average 2.56 kg cheese and 0.6 kg wool per ewe more than untreated controls. Our study confirms the reliability of the ABZ slow-release capsules over 90 days and the positive effect of treatment on nematode contamination of pasture and ewe productivity.

  20. Recurrent Hemorrhagic Pericardial Effusion and Tamponade due to Filariasis Successfully Treated with Ivermectin and Albendazole.

    PubMed

    Sinha, Santosh Kumar; Goel, Amit; Sachan, Mohit; Saraf, Sameer; Verma, Chandra Mohan

    2015-01-01

    Filariasis presenting with pericardial effusion with tamponade is rare. We report a case of a 30-year-old female who was admitted with severe dyspnea and chest pain since 2 days. Echocardiogram showed massive pericardial effusion with tamponade. Pericardial fluid aspiration drained 1.2 L of hemorrhagic fluid. Cytology examination revealed microfilaria of Wuchereria bancrofti. She was treated with diethyl carbamazine and discharged. Six weeks later, she presented again with massive pericardial effusion with cardiac tamponade. Pericardiocentesis was done. Cytology examination revealed microfilaria of W. bancrofti. This time she was treated with ivermectin and albendazole and cured. Hemorrhagic effusion resolved completely. Though relatively uncommon, tropical diseases must always be considered in the etiological diagnosis of recurrent pericardial effusion. PMID:26240733

  1. Studies on Pidotimod Enantiomers With Chiralpak-IA: Crystal Structure, Thermodynamic Parameters and Molecular Docking.

    PubMed

    Dou, Xiaorui; Su, Xin; Wang, Yue; Chen, Yadong; Shen, Weiyang

    2015-11-01

    Pidotimod, a synthetic dipeptide, has two chiral centers with biological and immunological activity. Its enantiomers were characterized by x-ray crystallographic analysis. A chiral stationary phase (CSP) Chiralpak-IA based on amylose derivatized with tris-(3, 5-dimethylphenyl carbamate) was used to separate pidotimod enantiomers. The mobile phase was prepared in a ratio of 35:65:0.2 of methyl-tert-butyl-ether and acetonitrile trifluoroaceticacid. In addition, thermodynamics and molecular docking methods were used to explain the enantioseparation mechanism by Chiralpak-IA. Thermodynamic studies were carried out from 10 to 45 °C. In general, both retention and enantioselectivity decreased as the temperature increased. Thermodynamic parameters indicate that the interaction force between the pidotimod enantiomer (4S, 2'R) and IA CSP is stronger and their complex model is more stable. According to GOLD molecular docking simulation, Van der Waals force is the leading cause of pidotimod enantiomers separation by IA CSP.

  2. CAPILLARY ELECTROPHORESIS FOR ENANTIOMER SEPARATION AND MEASUREMENT OF ENANTIOSELECTIVITY OF CHIRAL POLLUTANTS IN THE ENVIRONMENT

    EPA Science Inventory

    Chiral pollutants exist as 2 species, -- enantiomers - that have identical physical and chemical properties except when they interact with enzymes or other chiral molecules; then they usually react selectively. This enantioselectivity results in different rates of microbial trans...

  3. ANALYSIS OF THE ENANTIOMERS OF CHIRAL PESTICIDES AND OTHER POLLUTANTS IN ENVIRONMENTAL SAMPLES BY CAPILLARY ELECTROPHORESIS

    EPA Science Inventory

    The generic method described here involves typical capillary electrophoresis (CE) techniques, with the addition of cyclodextrin chiral selectors to the electrolyte for enantiomer separation and also, in the case of neutral analytes, the further addition of a micelle forming comp...

  4. The natural diterpene tonantzitlolone A and its synthetic enantiomer inhibit cell proliferation and kinesin-5 function.

    PubMed

    Pfeffer, Tobias J; Sasse, Florenz; Schmidt, Christoph F; Lakämper, Stefan; Kirschning, Andreas; Scholz, Tim

    2016-04-13

    Tonantzitlolone A, a diterpene isolated from the Mexican plant Stillingia sanguinolenta, shows cytostatic activity. Both the natural product tonantzitlolone A and its synthetic enantiomer induce monoastral spindle formation in cell experiments which indicates inhibitory activity on kinesin-5 mitotic motor molecules. These inhibitory effects on kinesin-5 could be verified in in vitro single-molecule motility assays, where both tonantzitlolones interfered with kinesin-5 binding to its cellular interaction partner microtubules in a concentration-dependent manner, yet with a larger effect of the synthetic enantiomer. In contrast to kinesin-5 inhibition, both tonantzitlolone A enantiomers did not affect conventional kinesin-1 function; hence tonantzitlolones are not unspecific kinesin inhibitors. The observed stronger inhibitory effect of the synthetic enantiomer demonstrates the possibility to enhance the overall moderate anti-proliferative effect of the lead compound tonantzitlolon A by chemical modification.

  5. HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC SEPARATION OF THE ENANTIOMERS OF ORGANOPHOSPHORUS PESTICIDES ON POLYSACCHARIDE CHIRAL STATIONARY PHASES

    EPA Science Inventory

    High-performance liquid chromatographic separation of the individual enantiomers of 12 organophosphorus pesticides (OPs) was obtained on polysaccharide enantioselective HPLC columns using alkane-alcohol mobile phase. The OP pesticides were crotoxyphos, dialifor, fonofos, fenamiph...

  6. Chiral discrimination of ofloxacin enantiomers using DNA double helix regulated by metal ions.

    PubMed

    Fu, Yan; Duan, Xiaoli; Chen, Xiongfei; Zhang, Haixiang; Zhang, Jinli; Li, Wei

    2014-05-01

    DNA-based chiral selectors are constructed to discriminate ofloxacin enantiomers through metal-ion anchoring on a special DNA double helix that contains successive GC pairs. The effects of metal ions involving Mg(2+), Ni(2+), Cu(2+), Ag(+), and Pt(2+) were studied on the regulation of DNA chiral discrimination towards ofloxacin enantiomers. It is shown that DNA-Cu(II) complexes exhibit the highest enantioselectivities at the [Cu(2+)]/base ratio of 0.1. The enantiomeric excess can reach 59% in R-enantiomer after being adsorbed by the RET-Cu(II) complex. Stereoselective recognition of ofloxacin enantiomers on the double helix is tunable via external stimulus, providing a programmable desorption process to regenerate DNA. This DNA-based chiral selector exhibits excellent reusability without apparent loss of enantioselectivity after three cycles of adsorption and desorption.

  7. Capillary electrophoresis to quantitate gossypol enantiomers in cotton flower petals and seed.

    PubMed

    Vshivkov, Sergey; Pshenichnov, Egor; Golubenko, Zamira; Akhunov, Alik; Namazov, Shadman; Stipanovic, Robert D

    2012-11-01

    Gossypol is a toxic compound that occurs as a mixture of enantiomers in cotton plant tissues including seed and flower petals. The (-)-enantiomer is more toxic to non-ruminant animals. Efforts to breed cottonseed with a low percentage of (-)-gossypol requires determination of the (+)- to (-)-gossypol ratio in seed and flower petals. We report a method to quantitatively determine the total gossypol and percent of its enantiomers in cotton tissues using high performance capillary electrophoresis (HPCE). The method utilizes a borate buffer at pH 9.3 using a capillary with internal diameter of 50μm, effective length of 24.5cm, 15kV and cassette temperature of 15°C. This method provides high accuracy and reproducible results with a limit of detection of the individual enantiomers of less than 36ng/mL providing base line separation in less than 6min. PMID:23122406

  8. Enantiomer excesses of rare and common sugar derivatives in carbonaceous meteorites.

    PubMed

    Cooper, George; Rios, Andro C

    2016-06-14

    Biological polymers such as nucleic acids and proteins are constructed of only one-the d or l-of the two possible nonsuperimposable mirror images (enantiomers) of selected organic compounds. However, before the advent of life, it is generally assumed that chemical reactions produced 50:50 (racemic) mixtures of enantiomers, as evidenced by common abiotic laboratory syntheses. Carbonaceous meteorites contain clues to prebiotic chemistry because they preserve a record of some of the Solar System's earliest (∼4.5 Gy) chemical and physical processes. In multiple carbonaceous meteorites, we show that both rare and common sugar monoacids (aldonic acids) contain significant excesses of the d enantiomer, whereas other (comparable) sugar acids and sugar alcohols are racemic. Although the proposed origins of such excesses are still tentative, the findings imply that meteoritic compounds and/or the processes that operated on meteoritic precursors may have played an ancient role in the enantiomer composition of life's carbohydrate-related biopolymers. PMID:27247410

  9. ABSOLUTE CONFIGURATION AND BIOLOGICAL PROPERTIES OF ENANTIOMERS OF CFTR INHIBITOR BPO-27.

    PubMed

    Snyder, David S; Tradtrantip, Lukmanee; Battula, Sailaja; Yao, Chenjuan; Phuan, Puay-Wah; Fettinger, James C; Kurth, Mark J; Verkman, A S

    2013-05-01

    We previously reported benzopyrimido-pyrrolo-oxazinedione (BPO) inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel and showed their efficacy in a model of polycystic kidney disease. Here, we separated the enantiomers of lead compound BPO-27, (1), which contains a single chiral center, and determined their absolute configuration, activity and metabolic stability. Following separation by chiral supercritical fluid chromatography, the R enantiomer, as determined by x-ray crystallography, inhibited CFTR chloride conductance with IC50 ~ 4 nM, while S enantiomer was inactive. In vitro metabolic stability in hepatic microsomes showed both enantiomers as stable, with <5 % metabolism in 4 h. Following bolus interperitoneal administration in mice, serum (R)-1 decayed with t1/2 ~ 1.6 h and gave sustained therapeutic concentrations in kidney.

  10. Studies on Pidotimod Enantiomers With Chiralpak-IA: Crystal Structure, Thermodynamic Parameters and Molecular Docking.

    PubMed

    Dou, Xiaorui; Su, Xin; Wang, Yue; Chen, Yadong; Shen, Weiyang

    2015-11-01

    Pidotimod, a synthetic dipeptide, has two chiral centers with biological and immunological activity. Its enantiomers were characterized by x-ray crystallographic analysis. A chiral stationary phase (CSP) Chiralpak-IA based on amylose derivatized with tris-(3, 5-dimethylphenyl carbamate) was used to separate pidotimod enantiomers. The mobile phase was prepared in a ratio of 35:65:0.2 of methyl-tert-butyl-ether and acetonitrile trifluoroaceticacid. In addition, thermodynamics and molecular docking methods were used to explain the enantioseparation mechanism by Chiralpak-IA. Thermodynamic studies were carried out from 10 to 45 °C. In general, both retention and enantioselectivity decreased as the temperature increased. Thermodynamic parameters indicate that the interaction force between the pidotimod enantiomer (4S, 2'R) and IA CSP is stronger and their complex model is more stable. According to GOLD molecular docking simulation, Van der Waals force is the leading cause of pidotimod enantiomers separation by IA CSP. PMID:26340373

  11. Enantiomer resolution by pressure increase: inferences from experimental and topological results for the binary enantiomer system (R)- and (S)-mandelic acid.

    PubMed

    Rietveld, Ivo B; Barrio, Maria; Tamarit, Josep-Lluis; Do, Bernard; Céolin, René

    2011-12-15

    In pharmacy, racemic compounds are often problematic, because generally only one of the enantiomers possesses therapeutic activity and it is often difficult to separate them. Even though this problem is likely as old as the pharmaceutical industry, one thermodynamically obvious way of separating racemic crystals has never been studied experimentally, which is by using pressure. Data have been obtained on the equilibria of the (R)- and (S)-mandelic acid system as a function of pressure and temperature. With the use of thermodynamic arguments including the Clapeyron, Schröder, and Prigogine-Defay equations, it has been demonstrated that the conglomerate (crystals of separated enantiomers) becomes more stable than the racemic compound at approximately 0.64 GPa and 460 K. Even though this pressure is still higher than at the bottom of the Mariana Trench, there are no technical obstacles to produce such conditions, making pressure a viable option for separating enantiomers.

  12. High-performance liquid chromatographic separation of the enantiomers of organophosphorus pesticides on polysaccharide chiral stationary phases.

    PubMed

    Ellington, J J; Evans, J J; Prickett, K B; Champion, W L

    2001-09-14

    High-performance liquid chromatographic separation of the individual enantiomers of 12 organophosphorus pesticides (OPs) was obtained on polysaccharide enantioselective HPLC columns using alkane-alcohol mobile phase. The OP pesticides were crotoxyphos, dialifor, fonofos, fenamiphos, fensulfothion, isofenphos, malathion, methamidophos, profenofos, crufomate, prothiophos and trichloronate. The enantiomers of fenamiphos, fensulfothion, profenofos and crufomate were separated on CHIRALPAK AD; the enantiomers of fenamiphos were also separated on CHIRALPAK AS; the enantiomers of methamidophos, crufomate and trichloronate were separated on CHIRALCEL OD; the enantiomers of crotoxyphos, dialifor, fonofos, malathion, prothiophos and trichloronate were separated on CHIRALCEL OJ; and the enantiomers of isofenphos were separated on CHIRALCEL OG. Baseline or partial separation of the enantiomers of six of these OP pesticides was obtained on CHIRALCEL OJ. In continued method development, the separation of the enantiomers of the 12 OPs was investigated more extensively on CHIRALCEL OJ to determine whether the mobile phase composition, flow-rate and column temperature could be optimized to yield at least partial separation of the enantiomers. Chromatographic conditions were found that gave either baseline or near baseline separations of the enantiomers of the 12 OPs on the CHIRALCEL OJ column. PMID:11587332

  13. [Morphofunctional changes in the digestive system of the nematode Passalurus ambiguus (Rudolphi, 1819) after use of the anthelmintics albendazole, fenbendazole, and ivermectin].

    PubMed

    Shirokova, E P; Chebyshev, N V

    2003-01-01

    The paper presents the results of histological and electron microscopic studies of the tissues of the digestive system of the nematode Passalurus ambiguus (Rudolphi, 1819) after use of the anthelminthics albendazole, fenbendazole, and ivermectine. They demonstrate that albendazole and fenbendazole cause irreversible structural changes. Less pronounced destruction of different parts of the digestive system occurs after the use of ivermectine. All the drugs affect the mid-gut of Passalurus. PMID:12886591

  14. In vitro anti-Giardia lamblia activity of 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and -pyrimidines, individually and in combination with albendazole.

    PubMed

    Velázquez-Olvera, Stephanía; Salgado-Zamora, Héctor; Jiménez-Cardoso, Enedina; Campos-Aldrete, Maria-Elena; Pérez-González, Cuauhtémoc; Ben Hadda, Taibi

    2016-03-01

    Giardiasis is a major diarrheal disease found throughout the world, the causative agent being the flagellate protozoan Giardia intestinalis. Infection is more common in children than in adults. The appearance of drug resistance has complicated the treatment of several parasitic diseases, including giardiasis. Thus, the aim of this investigation was to make an in vitro evaluation of the antigiardia response of synthetic derivatives 2-aryl-3-hydroxymethylimidazo[1,2-a]pyridines 1 and -pyrimidines 2 against trophozoites of Giardia lamblia WB, in comparison with the reference drug, albendazole. Additionally, the synergistic action of albendazole in combination with each of the most active 2-aryl-3-hydroxymethyl imidazo[1,2-a]pyridines and pyrimidines was also assessed. Based on the IC50 values obtained, the best anti-Giardia activity was provided by the 3-hydroxymethyl-4-fluorophenylimidazo[1,2-a]pyrimidine derivative 2c and the corresponding imidazo[1,2-a]pyrimidine with the p-tolyl substituent 2d, followed by 2a and 2b. These four compounds showed effectiveness at a concentration similar to that of albendazole. Regarding synergism, the IC50 of the combination of albendazole with 2a, 2b or 2c gave the best anti-Giardia action, showing greater efficacy than albendazole alone. Hence, G. lamblia WB showed high susceptibility to some 2-aryl-3-hydroxymethyl imidazo[1,2-a] pyrimidines, which acted synergistically when used in combination with albendazole. PMID:26657313

  15. Molecular Chirality: Enantiomer Differentiation by High-Resolution Spectroscopy

    NASA Astrophysics Data System (ADS)

    Hirota, Eizi

    2014-06-01

    I have demonstrated that triple resonance performed on a three-rotational-level system of a chiral molecule of C1 symmetry exhibits signals opposite in phase for different enantiomers, thereby making enantiomer differentiation possible by microwave spectroscopy This prediction was realized by Patterson et al. on 1,2-propanediol and 1,3-butanediol. We thus now add a powerful method: microwave spectroscopy to the study of chiral molecules, for which hitherto only the measurement of optical rotation has been employed. Although microwave spectroscopy is applied to molecules in the gaseous phase, it is unprecedentedly superior to the traditional method: polarimeter in resolution, accuracy, sensitivity, and so on, and I anticipate a new fascinating research area to be opened in the field of molecular chirality. More versatile and efficient systems should be invented and developed for microwave spectroscopy, in order to cope well with new applications expected for this method For C2 and Cn (n ≥ 3)chiral molecules, the three-rotational-level systems treated above for C1 molecules are no more available within one vibronic state. It should, however, be pointed out that, if we take into account an excited vibronic state in addition to the ground state, for example, we may encounter many three-level systems. Namely, either one rotational transition in the ground state is combined with two vibronic transitions, or such a rotational transition in an excited state may be connected through two vibronic transitions to a rotational level in the ground state manifold. The racemization obviously plays a crucial role in the study of molecular chirality. However, like many other terms employed in chemistry, this important process has been "defined" only in a vague way, in other words, it includes many kinds of processes, which are not well classified on a molecular basis. I shall mention an attempt to obviate these shortcomings in the definition of racemization and also to clarify the

  16. 21 CFR 524.981d - Fluocinolone acetonide, dimethyl sulfoxide solution.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... solution. 524.981d Section 524.981d Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.981d Fluocinolone acetonide, dimethyl sulfoxide solution. (a) Specifications. Each milliliter of solution contains 0.01 percent fluocinolone acetonide and 20 percent...

  17. Exploring the Use of a Guanine-Rich Catalytic DNA for Sulfoxide Preparation.

    PubMed

    Dellafiore, María A; Montserrat, Javier M; Iribarren, Adolfo M

    2015-01-01

    A guanine-rich DNA oligonucleotide complexed with hemin was used to catalyze controlled oxygen transfer reactions to different sulfides for sulfoxide preparation in the presence of H2O2. Comparable activities were obtained when using fully modified L-DNA. In addition, oligonucleotide immobilization led to an active catalyst which could be successfully recovered and reused without loss of activity.

  18. Exploring the Use of a Guanine-Rich Catalytic DNA for Sulfoxide Preparation

    PubMed Central

    Dellafiore, María A.; Montserrat, Javier M.; Iribarren, Adolfo M.

    2015-01-01

    A guanine-rich DNA oligonucleotide complexed with hemin was used to catalyze controlled oxygen transfer reactions to different sulfides for sulfoxide preparation in the presence of H2O2. Comparable activities were obtained when using fully modified L-DNA. In addition, oligonucleotide immobilization led to an active catalyst which could be successfully recovered and reused without loss of activity. PMID:26066510

  19. Full functionalization of the 7-azaindole scaffold by selective metalation and sulfoxide/magnesium exchange.

    PubMed

    Barl, Nadja M; Sansiaume-Dagousset, Elodie; Karaghiosoff, Konstantin; Knochel, Paul

    2013-09-16

    Filling positions: 7-Azaindoles are important targets in the pharmaceutical industry. All five carbon positions of the azaindole ring system can be functionalized in a predictable manner starting from the appropriately substituted azaindole 1 by directed metalation and halogen/magnesium and sulfoxide/magnesium exchange. The products are fully substituted azaindoles of type 2.

  20. Compartmentalization and Regulation of Mitochondrial Function by Methionine Sulfoxide Reductases in Yeast

    PubMed Central

    Kaya, Alaattin; Koc, Ahmet; Lee, Byung Cheon; Fomenko, Dmitri E.; Rederstorff, Mathieu; Krol, Alain; Lescure, Alain; Gladyshev, Vadim N.

    2010-01-01

    Elevated levels of reactive oxygen species can damage proteins. Sulfur-containing amino acid residues, cysteine and methionine, are particularly susceptible to such damage. Various enzymes evolved to protect proteins or repair oxidized residues, including methionine sulfoxide reductases MsrA and MsrB, which reduce methionine-S-sulfoxide (Met-SO), and methionine-R-sulfoxide (Met-RO) residues, respectively, back to methionine. Here, we show that MsrA and MsrB are involved in the regulation of mitochondrial function. Saccharomyces cerevisiae mutant cells lacking MsrA, MsrB or both proteins, had normal levels of mitochondria, but lower levels of cytochrome c and fewer respiration-competent mitochondria. The growth of single MsrA or MsrB mutants on respiratory carbon sources was inhibited, and that of the double mutant was severely compromised, indicating impairment of mitochondrial function. Although MsrA and MsrB are thought to have similar roles in oxidative protein repair each targeting a diastereomer of methionine sulfoxide, their deletion resulted in different phenotypes. GFP fusions of MsrA and MsrB showed different localization patterns and primarily localized to cytoplasm and mitochondria, respectively. This finding agreed with compartment-specific enrichment of MsrA and MsrB activities. These results show that oxidative stress contributes to mitochondrial dysfunction through oxidation of methionine residues in proteins located in different cellular compartments. PMID:20799725

  1. Prevalence of soil-transmitted helminths after mass albendazole administration in an indigenous community of the Manu jungle in Peru

    PubMed Central

    Cabada, Miguel M; Lopez, Martha; Arque, Eulogia; Clinton White, A

    2014-01-01

    Few data are available on the epidemiology of soil-transmitted helminths (STHs) in indigenous populations of the Peruvian Amazon. While albendazole is being increasingly used in deworming campaigns, few data exist on the impact of mass drug administration in isolated populations. We studied the prevalence of STHs, anemia, and malnutrition in a Matsigenka ethnic group from the Peruvian Amazon. Participants had received two doses of albendazole on consecutive days, 3 months before and again 2 weeks before data collection. Overall, 290 subjects were included. Most were female (53.7%) and 63.9% were ≤19 years old. Half of the participants had helminth infections. Trichiuris (30.2%), hookworm (19.1%), Ascaris (17.7%), and Strongyloides (5.6%) were the most common helminths. Other helminth ova included Capillaria hepatica and Fasciola-like eggs. Subjects of 5–19 years (51.8 %) and 20–35 years (68.6 %) old had helminths more often than those under 5 years (38%) and older than 35 years (41.5%) (P  =  0.02). Anemia was detected in 41% of children and this was more common in children under 5 years that in those of 5–19 years [odd ratio (OR)  =  5.68; 95% CI: 2.71–11.88]. Overall, 72.1% of children were malnourished. Stunting was common in children (70.7%), but wasting was not (2.9%). Despite repeated albendazole administration, this population continued to have a high prevalence of STHs, anemia, and malnutrition. In addition, we detected unusual organisms and organisms that do not respond to albendazole. Further studies are needed to assess the rationale and efficacy of mass chemotherapy for STHs in the Amazon. PMID:24934795

  2. Therapeutic efficacy of different brands of albendazole against soil transmitted helminths among students of Mendera Elementary School, Jimma, Southwest Ethiopia

    PubMed Central

    Tefera, Ephrem; Belay, Tariku; Mekonnen, Seleshi Kebede; Zeynudin, Ahmed; Belachew, Tefera

    2015-01-01

    Introduction Different brands Albendazole are commercially available and the efficacious brand/s is/are required for effective control of STHs infection. Thus, this study is aimed at determining the therapeutic efficacy of different brands of albendazole against soil transmitted helminths among school children of Jimma town. Methods A cross sectional survey for prevalence of geohelminths and a randomized trial for efficacy study of different brands of albendazole was conducted among students Mendera Elementary School from March 29 to April 29, 2010. Positive subjects were randomized into three treatment arms using lottery method. The collected stool samples were examined by the McMaster method. CRs were calculated using SPSS windows version 16 and ERRs were calculated using appropriate formula. Results Of the 715 school children who had their stools examined, 326 were positive for STHs with a prevalence rate of 45.6%. The cure rates (CR) for A. lumbricoides, T. trichiura and Hookworm were 99.4, 59.9 and 93.7%, respectively. Similarly, the egg reduction rates (ERR) were 97, 99.9 and 99.9% respectively. A statistical significant mean STH egg count difference were observed between pre and post-intervention study (p <0.001). But no statistical significant curing effect difference were observed among the three brands used against the three STHs (p >0.05). Conclusion All the three brands of Albendazole tested regardless of the brand type were therapeutically efficacious for Ascariasis, Trichuriasis and Hookworm infections irrespective of the infection status whether it was single or multiple. PMID:26958115

  3. Hookworm infection among school age children in Kintampo north municipality, Ghana: nutritional risk factors and response to albendazole treatment.

    PubMed

    Humphries, Debbie; Simms, Benjamin T; Davey, Dylan; Otchere, Joseph; Quagraine, Josephine; Terryah, Shawn; Newton, Samuel; Berg, Elyssa; Harrison, Lisa M; Boakye, Daniel; Wilson, Michael; Cappello, Michael

    2013-09-01

    Children (n = 812) 6-11 years of age attending 16 schools in the Kintampo North Municipality of Ghana were screened for participation in a study on hookworm infection, nutrition, and response to albendazole. The prevalence of Necator americanus hookworm infection (n = 286) was 39.1%, and significant predictors of infection included age, malaria parasitemia, lack of health care, school area, levels of antibodies against hookworm, and low consumption of animal foods. The cure rate after a single dose (400 mg) albendazole was 43%, and the mean fecal egg count reduction rate was 87.3%. Data for an in vitro egg hatch assay showed a trend toward reduced albendazole susceptibility in post-treatment hookworm isolates (P = 0.06). In summary, hookworm infection is prevalent among school age children in the Kintampo North Municipality and animal food intake inversely correlates with infection status. Modest cure rates and fecal egg count reduction rates reinforce the need for further investigation of potential benzimidazole resistance in Ghana.

  4. Modified β-Cyclodextrin Inclusion Complex to Improve the Physicochemical Properties of Albendazole. Complete In Vitro Evaluation and Characterization

    PubMed Central

    García, Agustina; Leonardi, Darío; Salazar, Mario Oscar; Lamas, María Celina

    2014-01-01

    The potential use of natural cyclodextrins and their synthetic derivatives have been studied extensively in pharmaceutical research and development to modify certain properties of hydrophobic drugs. The ability of these host molecules of including guest molecules within their cavities improves notably the physicochemical properties of poorly soluble drugs, such as albendazole, the first chosen drug to treat gastrointestinal helminthic infections. Thus, the aim of this work was to synthesize a beta cyclodextrin citrate derivative, to analyze its ability to form complexes with albendazole and to evaluate its solubility and dissolution rate. The synthesis progress of the cyclodextrin derivative was followed by electrospray mass spectrometry and the acid-base titration of the product. The derivative exhibited an important drug affinity. Nuclear magnetic resonance experiments demonstrated that the tail and the aromatic ring of the drug were inside the cavity of the cyclodextrin derivative. The inclusion complex was prepared by spray drying and full characterized. The drug dissolution rate displayed exceptional results, achieving 100% drug release after 20 minutes. The studies indicated that the inclusion complex with the cyclodextrin derivative improved remarkably the physicochemical properties of albendazole, being a suitable excipient to design oral dosage forms. PMID:24551084

  5. Hookworm Infection among School Age Children in Kintampo North Municipality, Ghana: Nutritional Risk Factors and Response to Albendazole Treatment

    PubMed Central

    Humphries, Debbie; Simms, Benjamin T.; Davey, Dylan; Otchere, Joseph; Quagraine, Josephine; Terryah, Shawn; Newton, Samuel; Berg, Elyssa; Harrison, Lisa M.; Boakye, Daniel; Wilson, Michael; Cappello, Michael

    2013-01-01

    Children (n = 812) 6–11 years of age attending 16 schools in the Kintampo North Municipality of Ghana were screened for participation in a study on hookworm infection, nutrition, and response to albendazole. The prevalence of Necator americanus hookworm infection (n = 286) was 39.1%, and significant predictors of infection included age, malaria parasitemia, lack of health care, school area, levels of antibodies against hookworm, and low consumption of animal foods. The cure rate after a single dose (400 mg) albendazole was 43%, and the mean fecal egg count reduction rate was 87.3%. Data for an in vitro egg hatch assay showed a trend toward reduced albendazole susceptibility in post-treatment hookworm isolates (P = 0.06). In summary, hookworm infection is prevalent among school age children in the Kintampo North Municipality and animal food intake inversely correlates with infection status. Modest cure rates and fecal egg count reduction rates reinforce the need for further investigation of potential benzimidazole resistance in Ghana. PMID:23836564

  6. The chiral herbicide beflubutamid (I): Isolation of pure enantiomers by HPLC, herbicidal activity of enantiomers, and analysis by enantioselective GC-MS.

    PubMed

    Buerge, Ignaz J; Bächli, Astrid; De Joffrey, Jean-Pierre; Müller, Markus D; Spycher, Simon; Poiger, Thomas

    2013-07-01

    For many chiral pesticides, little information is available on the properties and fate of individual stereoisomers. A basic data set would, first of all, include stereoisomer-specific analytical methods and data on the biological activity of stereoisomers. The herbicide beflubutamid, which acts as an inhibitor of carotenoid biosynthesis, is currently marketed as racemate against dicotyledonous weeds in cereals. Here, we present analytical methods for enantiomer separation of beflubutamid and two metabolites based on chiral HPLC. These methods were used to assign the optical rotation and to prepare milligram quantities of the pure enantiomers for further characterization with respect to herbicidal activity. In addition, sensitive analytical methods were developed for enantiomer separation and quantification of beflubutamid and its metabolites at trace level, using chiral GC-MS. In miniaturized biotests with garden cress, (-)-beflubutamid showed at least 1000× higher herbicidal activity (EC50, 0.50 μM) than (+)-beflubutamid, as determined by analysis of chlorophyll a in 5-day-old leaves. The agricultural use of enantiopure (-)-beflubutamid rather than the racemic compound may therefore be advantageous from an environmental perspective. In further biotests, the (+)-enantiomer of the phenoxybutanoic acid metabolite showed effects on root growth, possibly via an auxin-type mode of action, but at 100× higher concentrations than the structurally related herbicide (+)-mecoprop. PMID:22849576

  7. 1,1′:4′,1′′-Terphenyl-2′,5′-dicarb­oxy­lic acid dimethyl sulfoxide-d 6 disolvate

    PubMed Central

    Pop, Lucian C.; Preite, Marcelo; Manriquez, Juan Manuel; Vega, Andrés; Chavez, Ivonne

    2012-01-01

    The asymmetric unit of the title solvate, C20H14O4·2C2D6OS, contains half of the substituted terephthalic acid mol­ecule and one solvent mol­ecule. The centroid of the central benzene ring in the acid mol­ecule is coincident with a crystallographic inversion center. Neither the carboxyl nor the phenyl substituents are coplanar with the central aromatic ring, showing dihedral angles of 53.18 (11) and 47.83 (11)°, respectively. The dimethyl sulfoxide solvent mol­ecules are hydrogen bonded to the carb­oxy­lic acid groups. PMID:22606132

  8. Life detection using glucose and tetrasaccharide enantiomer pairs.

    PubMed

    Warmflash, David; Chu, Huanyi; Siefert, Johnathan; Fox, George E

    2009-04-01

    A life-detection system based on the expectation that any viable organism will utilize stereoisomers of a given compound asymmetrically is examined. Aqueous extracts of common soil, Mars regolith simulant JSC Mars-1, and suspensions of E. coli and S. cerevisiae were incubated with stereoisomer pairs. The enantiomeric pairs were either D- and L-glucose or a pair of chiral tetrasaccharides. Following an incubation period of 10 days, stereoisomeric selectivity is detectable with the glucose pair by mass spectrometry in extracts made from soil at 0.5 g/ml, in extracts made from JSC Mars-1 at 2.5 g/ml, and in cell suspensions down to 1.0 x 10(7) cells/ml. For the tetrasaccharide pair, stereoisomeric selectivity was detected in extracts made from 0.5 g/ml or more of common soil but not in JSC Mars-1 simulant. The effective sensitivity in extracts was 2.5 x 10(7) cells/ml or better for the glucose pair and 5.0 x 10(8) cells/ml or better for the tetrasaccharide pair. The sensitivity of the glucose pair was such that it could detect life in samples that would be found to be devoid of organic matter by the GCMS system carried by the Viking landers. The results demonstrate the utility of the approach in the search for biological activity on Mars. However, sensitivity is a function of the enantiomer pair used, and this might also be different for hypothetical martian organisms. Therefore, it will be necessary to characterize additional stereoisomeric pairs and, ultimately, to include several in a single test environment. PMID:19499996

  9. Surface mediated chiral interactions between cyclodextrins and propranolol enantiomers: a SERS and DFT study.

    PubMed

    Stiufiuc, Rares; Iacovita, Cristian; Stiufiuc, Gabriela; Bodoki, Ede; Chis, Vasile; Lucaciu, Constantin M

    2015-01-14

    The nanoparticles mediated enantioselective recognition of propranolol enantiomers through native cyclodextrin complexation has been investigated by using surface-enhanced Raman spectroscopy (SERS). The highly efficient chiral recognition mechanism is based on a synergistic interaction between spherical noble metal nanoparticles, propranolol enantiomers and native cyclodextrins (CDs). Amongst the native cyclodextrins, β-CD has the highest chiral recognition ability for propranolol enantiomers, due to its specific shape and cavity size, thus producing the largest difference between the recorded SERS spectra of the two hosted enantiomers. The molecular interaction mechanism responsible for enantioselectivity was furthermore proven by quantum chemical calculations based on density functional theory (DFT). The theoretical calculations and experimental SER spectra allowed the assignment of functional moieties involved in the chiral recognition mechanism. The most important factors governing the highly efficient chiral probing by SERS are the fundamentally different mechanism of interaction between the R- and S-enantiomers and β-CD and the strength of interaction between the nanoparticle surface and the two propranolol-CD complexes. The role of metallic nanoparticles in the enantioselective recognition process has been experimentally evaluated by using silver and gold nanoparticles as SERS substrates, given their ability to interact differently with the complexes. The viability of this new method for chiral discrimination has been demonstrated for both substrates and could open new avenues for these kinds of applications.

  10. Quantitative Determination of Lercanidipine Enantiomers in Commercial Formulations by Capillary Electrophoresis

    PubMed Central

    Lourenço, Luciana Pereira; Aguiar, Fernando Armani; de Oliveira, Anderson Rodrigo Moraes; de Gaitani, Cristiane Masetto

    2015-01-01

    An enantioselective method based on capillary electrophoresis (CE) using cyclodextrin (CD) as chiral selector was developed and validated for determination of lercanidipine (LER) enantiomers, a drug calcium channel blocker which exerts antihypertensive effects of long duration, in a pharmaceutical formulation. Optimum separation of LER enantiomers was obtained on a 50 cm × 50 μm id capillary using a sodium acetate buffer solution 200 mmol/L pH 4.0 containing 10 mmol/L of 2,3,6-o-methyl-β-cyclodextrin (TM-β-CD) as background electrolyte. The capillary temperature and voltage were 15°C and 25 kV, respectively, hydrodynamic injection and detection at 237 nm. Linearity was obtained in the range 12.5–100 μg/mL for both enantiomers (r ≥ 0.995). The RSD (%) and relative errors (E, %) obtained in precision and accuracy studies (intraday and interday) were lower than 5%. After validation, the method was applied to quantify the enantiomers of LER in commercial tablets and the results were satisfactory in terms of accuracy and precision, both less than 5%. Therefore, this method was found to be appropriate for enantioselective quality control of LER enantiomers in pharmaceutical formulations. PMID:25821632

  11. Differential field responses of the little fire ant, Wasmannia auropunctata (Roger), to alarm pheromone enantiomers.

    PubMed

    Yu, Yang; Jang, Eric B; Siderhurst, Matthew S

    2014-12-01

    The little fire ant, Wasmannia auropunctata (Roger) (Hymenoptera: Formicidae), is an invasive ant with negative impacts on both biodiversity and agriculture throughout the tropics and subtropics. Field experiments were conducted in order to elucidate the relative attractiveness of the enantiomers of the alarm pheromones, 2,5-dimethyl-3-(2-methylbutyl)pyrazine and 3-methyl-2-(2-methylbutyl)pyrazine. The enantiomers tested were synthesized from commercially available (S)-2-methylbutan-1-ol or kinetically resolved (R)-2-methylbutan-1-ol, prepared using Pseudomonas cepacia lipase (PCL). Bioassays conducted in a macadamia orchard on the island of Hawaii demonstrated that W. auropunctata were preferentially attracted to the (S)-enantiomers of both alkyl pyrazines over the racemic mixtures in all experiments. To our knowledge, this is the first instance of differential attraction of ants to the enantiomers of chiral pyrazine pheromones despite many examples of these compounds in the literature. In addition, using a chiral column it was determined that (S)-2,5-dimethyl-3-(2-methylbutyl)pyrazine and (S)-3-methyl-2-(2-methylbutyl)pyrazine are the only enantiomers produced by W. auropunctata. PMID:25370918

  12. Indirect chiral separation of tryptophan enantiomers by high performance liquid chromatography with indirect chemiluminiscence detection.

    PubMed

    Zhou, Jie; Chen, Shanshan; Sun, Fang; Luo, Pei; Du, Qiuzheng; Zhao, Suzhen

    2015-12-01

    In recent years, the study of chiral compounds in vivo has received much attention. In this study, a novel method based on high performance liquid chromatography (HPLC) coupled with chemiluminescence (CL) detection was developed for the separation of tryptophan (Trp) enantiomers. o-Phthalaldehyde and N-acetyl-l-cysteine were used as chiral derivatization reagents for Trp before it can be detected by HPLC-CL method. The separation was carried out on an ODS column using a mobile phase composed of methanol-0.01mol/L phosphate buffer (40/60, v/v). Under the optimum conditions, satisfactory results were obtained, including complete separation, good relative standard deviations and low detection limits. The applicability of the proposed method has been validated by determining Trp in biological samples. Linear responses (r>0.9990) were observed over the range of 2.5×10(-7) to 1.2×10(-5)g/mL of Trp enantiomers, with quantitation limit of 2.5×10(-7)g/mL. The assay method shows good specificity to Trp enantiomers, and thus it will have great potential application in clinical diagnosis. The mean extraction efficiency of Trp enantiomers in mice plasma samples were 98.48% and 97.40%, respectively. The mean relative standard deviation (RSD) of Trp enantiomers were <3%. PMID:26523665

  13. Self-dispersible nanocrystals of albendazole produced by high pressure homogenization and spray-drying.

    PubMed

    Paredes, Alejandro Javier; Llabot, Juan Manuel; Sánchez Bruni, Sergio; Allemandi, Daniel; Palma, Santiago Daniel

    2016-10-01

    Albendazole (ABZ) is a broad-spectrum antiparasitic drug used in the treatment of human or animal infections. Although ABZ has shown a high efficacy for repeated doses in monogastric mammals, its low aqueous solubility leads to erratic bioavailability. The aim of this work was to optimize a procedure in order to obtain ABZ self-dispersible nanocrystals (SDNC) by combining high pressure homogenization (HPH) and spray-drying (SD). The material thus obtained was characterized and the variables affecting both the HPH and SD processes were studied. As expected, the homogenizing pressure and number of cycles influenced the final particle size, while the stabilizer concentration had a strong impact on SD output and redispersion of powders upon contact with water. ABZ SDNC were successfully obtained with high process yield and redispersibility. The characteristic peaks of ABZ were clearly identified in the X-ray patterns of the processed samples. A noticeable increase in the dissolution rate was observed in the aqueous environment. PMID:26856301

  14. Effectiveness of Ivermectin and Albendazole against Haemonchus contortus in Sheep in West Java, Indonesia

    PubMed Central

    Puspitasari, Silvia; Farajallah, Achmad; Sulistiawati, Erni; Muladno

    2016-01-01

    Administering a half dose of an anthelmintic is a simple method for detecting resistance in parasites infesting small ruminants. When a single anthelmintic fails in native sheep from Indonesia, a combination of anthelmintics from different chemical classes with different modes of action are administered as an alternative parasite-control strategy. This study compared the anthelmintic efficacy of ivermectin (IVM) and albendazole (ABZ) given either separately as a single dose or half dose or co-administered to sheep naturally infected with Haemonchus contortus. Twelve sheep from Bogor, West Java, Indonesia were divided into the following six treatment groups: half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, combined IVM + ABZ, and control. The treatment efficacy was determined using the faecal egg count reduction test (FECRT) at day 0 (pre-treatment) and post-treatment at days 7, 14, 21, 28, 35, and 42. The efficacies of half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, and the combination treatment ranged from −1900% to 100%, 99% to 100%, −167% to 100%, −467% to 89%, and −200% to 100%, respectively. The FECRT for the half-dose IVM, half-dose ABZ, full-dose ABZ showed that H. contortus is resistant to half-dose IVM and ABZ. Full-dose IVM was effective against H. contortus. The combined treatment was more effective against H. contortus than ABZ alone. PMID:27019686

  15. In vitro effect of praziquantel and albendazole combination therapy on the larval stage of Echinococcus granulosus.

    PubMed

    Urrea-París, M A; Moreno, M J; Casado, N; Rodriguez-Caabeiro, F

    2000-12-01

    Protoscolices of Echinococcus granulosus were incubated in vitro with praziquantel (PZ), albendazole (ABZ), or a combination of both (PZ + ABZ). PZ and ABZ displayed slower protoscolicidal activity when applied separately than when used in combination. Despite the low PZ + ABZ concentrations used, protoscolex viability dropped rapidly (within 15 days). At this time, cysts did not develop following their inoculation into mice. The ultrastructural changes induced in the protoscolices by PZ + ABZ were (a) the loss of sucker concavity, (b tegumental contraction of the soma region, (c) the formation of digitiform tegumental extensions, (d) destruction of the tegument, and (e) the degeneration of parenchyma cells as reflected by the presence of numerous lamellar bodies. The PZ + ABZ treatment was effective only against small cysts, which had collapsed at 10 days postinoculation (p.i.). This treatment caused the following alterations: (a) loss of cyst turgidity at 6 days p.i.; (b) separation of the laminated and germinal layers; (c) loss of microtriches; (d) the appearance of numerous lipid droplets in the inner region of the germinal layer, (e) vacuolation of the cyton cytoplasm; and (f) the formation of abundant autophagosomes, which finally led to loss of the integrity of the germinal layer.

  16. In vitro and in vivo treatments of Echinococcus granulosus with Huaier aqueous extract and albendazole liposome.

    PubMed

    Lv, Hailong; Jiang, Yufeng; Liao, Min; Sun, Hongli; Zhang, Shijie; Peng, Xinyu

    2013-01-01

    The aim of this study was to investigate the in vitro and in vivo efficacies of chemotherapy employing albendazole liposome (L-ABZ), Huaier aqueous extract, and a Huaier aqueous extract/L-ABZ combination against Echinococcus granulosus. Protoscolices of E. granulosus were incubated in vitro with the two drugs, either separately or in combination, at the following final concentrations: 2 mg/mL Huaier aqueous extract, 10 μg/mL L-ABZ, and 2 mg/mL Huaier aqueous extract + 10 μg/mL L-ABZ. Huaier aqueous extract and L-ABZ displayed slower protoscolicidal activity when applied separately than when used in combination. The maximum protoscolicidal effect was found with the combination Huaier aqueous extract + L-ABZ. Despite the low Huaier aqueous extract + L-ABZ concentrations used, protoscolex viability dropped rapidly. In vivo studies were performed on mice injected with protoscolices of E. granulosus. Huaier aqueous extract and L-ABZ were administered three times a week for a period of 4 months by the oral route. Huaier aqueous extract in E. granulosus-infected mice was effective. Combined application of both drugs did increase the treatment efficacy. In conclusion, the outcomes obtained clearly demonstrated that in vitro and in vivo treatment with Huaier aqueous extract and L-ABZ is effective against E. granulosus.

  17. Investigation of the complexation of albendazole with cyclodextrins for the design of new antiparasitic formulations.

    PubMed

    Pradines, Bénédicte; Gallard, Jean-François; Iorga, Bogdan I; Gueutin, Claire; Loiseau, Philippe M; Ponchel, Gilles; Bouchemal, Kawthar

    2014-10-29

    Albendazole (ABZ) exhibits a potent antiparasitic activity against a broad spectrum of parasites. Unfortunately, the very low water solubility of ABZ (0.2 μg mL(-1), 0.7 μM) impairs considerably its formulation. Phase solubility diagrams showed that α-cyclodextrin (10% w/w), hydroxypropyl-β-cyclodextrin (40% w/w) and sulfobutylether-β-cyclodextrin (40% w/w) allowed an increase of apparent solubility with enhancement factors of 570, 3970, and 5880, respectively. The apparent aqueous solubility of ABZ was markedly increased from 0.2 μg mL(-1) (0.7 μM) without cyclodextrins to 1.52 mg mL(-1) (5.69 mM) with random methyl-β-cyclodextrin (Me-β-CD) (40% w/w). This corresponds to an apparent solubility enhancement factor of 7600 which is the maximal enhancement factor of ABZ apparent aqueous solubility ever reported in the literature using conventional cyclodextrins. The complexation mechanism between ABZ and cyclodextrins has been investigated using phase solubility diagrams, nuclear magnetic resonance ((1)H NMR) coupled with two-dimensional nuclear Overhauser effect (NOESY) experiments and molecular docking calculations. The results showed that the central bicyclic fragment from ABZ interacts with Me-β-CD according to 1:1 stoichiometry.

  18. Antiproliferative effect of benzimidazole anthelmintics albendazole, ricobendazole, and flubendazole in intestinal cancer cell lines.

    PubMed

    Králová, Věra; Hanušová, Veronika; Staňková, Petra; Knoppová, Kateřina; Čáňová, Kristýna; Skálová, Lenka

    2013-10-01

    This study aimed to test the antiproliferative effect of three benzimidazole anthelmintics in intestinal cancer cells and to investigate whether these drugs, which inhibit tubulin polymerization, can potentiate the efficacy of the microtubule-stabilizing drug paclitaxel (PTX). Four intestinal cancer cell lines, SW480, SW620, HCT8, and Caco2, with different origins and growth characteristics were used. The antiproliferative effect of albendazole (ABZ), ricobendazole (RBZ), flubendazole (FLU), and their combinations with PTX was tested using three different end-point viability assays, cell cycle distribution analysis, and the x-CELLigence System for real-time cell analysis. ABZ and FLU inhibited cell proliferation significantly in a concentration-dependent and time-dependent manner through cell arrest in the G2/M phase. RBZ was not effective at any concentration tested. The cell lines differed in sensitivity to FLU and ABZ, with HCT8 being the most sensitive, showing IC₅₀ values for ABZ and FLU that reached 0.3 and 0.9 μmol/l, respectively. Combinations of PTX+ABZ and PTX+FLU decreased cell viability more effectively when compared with treatment with individual drugs alone. The anthelmintic benzimidazole drugs ABZ and FLU show a significant cytostatic effect and potentiate the efficacy of PTX in intestinal cancer cells.

  19. Effectiveness of Ivermectin and Albendazole against Haemonchus contortus in Sheep in West Java, Indonesia.

    PubMed

    Puspitasari, Silvia; Farajallah, Achmad; Sulistiawati, Erni; Muladno

    2016-02-01

    Administering a half dose of an anthelmintic is a simple method for detecting resistance in parasites infesting small ruminants. When a single anthelmintic fails in native sheep from Indonesia, a combination of anthelmintics from different chemical classes with different modes of action are administered as an alternative parasite-control strategy. This study compared the anthelmintic efficacy of ivermectin (IVM) and albendazole (ABZ) given either separately as a single dose or half dose or co-administered to sheep naturally infected with Haemonchus contortus. Twelve sheep from Bogor, West Java, Indonesia were divided into the following six treatment groups: half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, combined IVM + ABZ, and control. The treatment efficacy was determined using the faecal egg count reduction test (FECRT) at day 0 (pre-treatment) and post-treatment at days 7, 14, 21, 28, 35, and 42. The efficacies of half-dose IVM, full-dose IVM, half-dose ABZ, full-dose ABZ, and the combination treatment ranged from -1900% to 100%, 99% to 100%, -167% to 100%, -467% to 89%, and -200% to 100%, respectively. The FECRT for the half-dose IVM, half-dose ABZ, full-dose ABZ showed that H. contortus is resistant to half-dose IVM and ABZ. Full-dose IVM was effective against H. contortus. The combined treatment was more effective against H. contortus than ABZ alone.

  20. A novel hot-melt extrusion formulation of albendazole for increasing dissolution properties.

    PubMed

    Martinez-Marcos, Laura; Lamprou, Dimitrios A; McBurney, Roy T; Halbert, Gavin W

    2016-02-29

    The main aim of the research focused on the production of hot-melt extrusion (HME) formulations with increased dissolution properties of albendazole (ABZ). Therefore, HME was applied as a continuous manufacturing technique to produce amorphous solid dispersions of the poorly water soluble drug ABZ combined with the polymer matrix polyvinylpyrrolidone PVP K12. HME formulations of ABZ-PVP K12 comprised a drug content of 1%, 5% and 10% w/w. The main analytical characterisation techniques used were scanning electron microscopy (SEM), micro-computed tomography (μ-CT), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and dissolution profile studies. The application of SEM, XRPD and DSC evidenced drug physical transformation from crystalline to amorphous state and therefore, the achievement of an amorphous solid dispersion. The introduction of a novel technique, μ-CT, to characterise the internal structure of these materials revealed key information regarding materials distribution and void content. Dissolution profile studies evidenced a high increase in drug release profile compared to pure ABZ. These promising results can lead to a great enhancement of the oral bioavailability of ABZ dosage forms. Therefore, HME is a potential continuous manufacturing technique to overcome ABZ poor solubility properties and lead to a significant increase in the therapeutic effect. PMID:26768722

  1. Evidence of Fasciola spp. resistance to albendazole, triclabendazole and bromofenofos in water buffaloes (Bubalus bubalis).

    PubMed

    Venturina, Virginia M; Alejandro, Ma Antonette F; Baltazar, Cyril P; Abes, Nancy S; Mingala, Claro N

    2015-01-01

    Fasciolosis caused by Fasciola spp. is considered the most important helminth infection of ruminants in tropical countries. Anthelmintic resistance has become a global concern. This study compared the efficacy of the commonly used anthelmintics, determined the toxicity level and any indication of resistance. Thirty two water buffaloes naturally-infected with Fasciola spp. were used to determine the efficacy of triclabendazole (TBZ), albendazole (ABZ), and bromofenofos (BRO) using Fecal Egg Count Reduction Test (FECRT). To test the toxicity of the drugs given, serum glutamic-pyruvic transaminase (SGPT) was evaluated before and within one week after treatment. One dose administration of ABZ registered an efficacy of 79.17%, 73.33% for TBZ and 70.83% for BRO. Efficacy in two dose- treatment group was 83.33% for both BRO and ABZ, and 90.00% for TBZ. Two dose-treatment was effective for TBZ (90%), ineffective for BRO and ABZ. SGPT levels were not significantly different between pre-treatment and post- treatment across all treatments. Giving one or two doses of anthelmintics, at one month interval, does not increase the efficacy of the three drugs tested. The study also implies that anthelmintic resistance may have developed in the animals.

  2. Evidence of Fasciola spp. resistance to albendazole, triclabendazole and bromofenofos in water buffaloes (Bubalus bubalis).

    PubMed

    Venturina, Virginia M; Alejandro, Ma Antonette F; Baltazar, Cyril P; Abes, Nancy S; Mingala, Claro N

    2015-01-01

    Fasciolosis caused by Fasciola spp. is considered the most important helminth infection of ruminants in tropical countries. Anthelmintic resistance has become a global concern. This study compared the efficacy of the commonly used anthelmintics, determined the toxicity level and any indication of resistance. Thirty two water buffaloes naturally-infected with Fasciola spp. were used to determine the efficacy of triclabendazole (TBZ), albendazole (ABZ), and bromofenofos (BRO) using Fecal Egg Count Reduction Test (FECRT). To test the toxicity of the drugs given, serum glutamic-pyruvic transaminase (SGPT) was evaluated before and within one week after treatment. One dose administration of ABZ registered an efficacy of 79.17%, 73.33% for TBZ and 70.83% for BRO. Efficacy in two dose- treatment group was 83.33% for both BRO and ABZ, and 90.00% for TBZ. Two dose-treatment was effective for TBZ (90%), ineffective for BRO and ABZ. SGPT levels were not significantly different between pre-treatment and post- treatment across all treatments. Giving one or two doses of anthelmintics, at one month interval, does not increase the efficacy of the three drugs tested. The study also implies that anthelmintic resistance may have developed in the animals. PMID:26878627

  3. Sulfoxide-Based Enantioselective Nazarov Cyclization: Divergent Syntheses of (+)-Isopaucifloral F, (+)-Quadrangularin A, and (+)-Pallidol.

    PubMed

    Tang, Mei-Lin; Peng, Peng; Liu, Zheng-Yu; Zhang, Jian; Yu, Jian-Ming; Sun, Xun

    2016-10-01

    The synthesis of enantiomerically pure 3-aryl substituted indanones is developed using an enantioselective sulfoxide-based Knoevenagel condensation/Nazarov cyclization procedure. After the reductive desulfonation of the methyl para-tolyl sulfoxide-containing chiral auxiliary under mild conditions, selected enantiomerically pure indanone is used for the divergent total syntheses of three resveratrol natural products (+)-isopaucifloral F, (+)-quadrangularin A, and (+)-pallidol. PMID:27490335

  4. Sulfoxide-Directed Metal-Free ortho-Propargylation of Aromatics and Heteroaromatics.

    PubMed

    Eberhart, Andrew J; Shrives, Harry J; Álvarez, Estela; Carrër, Amandine; Zhang, Yuntong; Procter, David J

    2015-05-11

    A sulfoxide-directed, metal-free ortho-propargylation of aromatics and heteroaromatics exploits intermolecular delivery of a propargyl nucleophile to sulfur followed by an intramolecular relay to carbon. The operationally simple cross-coupling procedure is general, regiospecific with regard to the propargyl nucleophile, and shows complete selectivity for products of ortho-propargylation over allenylation. The use of secondary propargyl silanes allows metal-free ortho-coupling to form carbon-carbon bonds between aromatic and heteroaromatic rings and secondary propargylic centres. The 'safety-catch' nature of the sulfoxide directing group is illustrated in a selective, iterative double cross-coupling process. The products of propargylation are versatile intermediates and they have been readily converted into substituted benzothiophenes.

  5. Sulfoxide-Directed Metal-Free ortho-Propargylation of Aromatics and Heteroaromatics

    PubMed Central

    Eberhart, Andrew J; Shrives, Harry J; Álvarez, Estela; Carrër, Amandine; Zhang, Yuntong; Procter, David J

    2015-01-01

    A sulfoxide-directed, metal-free ortho-propargylation of aromatics and heteroaromatics exploits intermolecular delivery of a propargyl nucleophile to sulfur followed by an intramolecular relay to carbon. The operationally simple cross-coupling procedure is general, regiospecific with regard to the propargyl nucleophile, and shows complete selectivity for products of ortho-propargylation over allenylation. The use of secondary propargyl silanes allows metal-free ortho-coupling to form carbon–carbon bonds between aromatic and heteroaromatic rings and secondary propargylic centres. The ‘safety-catch’ nature of the sulfoxide directing group is illustrated in a selective, iterative double cross-coupling process. The products of propargylation are versatile intermediates and they have been readily converted into substituted benzothiophenes. PMID:25752800

  6. LIQUID CHROMATOGRAPHIC SEPARATION OF THE ENANTIOMERS OF TRANS-CHLORDANE, CIS-CHLORDANE, HEPTACHLOR, HEPTACHLOR EPOXIDE AND ALPHA-HEXACHLOROCYCLOHEXANE WITH APPLICATION TO SMALL-SCALE PREPARATIVE SEPARATION

    EPA Science Inventory

    Analytical high-performance liquid chromatographic separations of the individual enantiomers of five polychlorinated compounds were obtained on polysaccharide stereoselective HPLC columns. The enantiomers of the pesticides trans-chlordane, cis-chlordane and heptachlor were separa...

  7. Engineering Cyclodextrin Clicked Chiral Stationary Phase for High-Efficiency Enantiomer Separation

    NASA Astrophysics Data System (ADS)

    Tang, Jian; Zhang, Shapopeng; Lin, Yuzhou; Zhou, Jie; Pang, Limin; Nie, Xuemei; Zhou, Baojing; Tang, Weihua

    2015-08-01

    The separation of racemic molecules is of crucial significance not only for fundamental research but also for technical application. Enantiomers remain challenging to be separated owing to their identical physical and chemical properties in achiral environments. Chromatographic techniques employing chiral stationary phases (CSPs) have been developed as powerful tools for the chiral analysis and preparation of pure enantiomers, most of which are of biological and pharmaceutical interests. Here we report our efforts in developing high-performance phenylcarbamated cyclodextrin (CD) clicked CSPs. Insights on the impact of CD functionalities in structure design are provided. High-efficiency enantioseparation of a range of aryl alcohols and flavanoids with resolution values (Rs) over 10 were demonstrated by per(3-chloro-4-methyl)phenylcarbamated CD clicked CSP. Comparison study and molecular simulations suggest the improved enantioselectivity was attributed to higher interactions energy difference between the complexes of enantiomers and CSPs with phenylcarbamated CD bearing 3-chloro and 4-methyl functionalities.

  8. Engineering Cyclodextrin Clicked Chiral Stationary Phase for High-Efficiency Enantiomer Separation

    PubMed Central

    Tang, Jian; Zhang, Shapopeng; Lin, Yuzhou; Zhou, Jie; Pang, Limin; Nie, Xuemei; Zhou, Baojing; Tang, Weihua

    2015-01-01

    The separation of racemic molecules is of crucial significance not only for fundamental research but also for technical application. Enantiomers remain challenging to be separated owing to their identical physical and chemical properties in achiral environments. Chromatographic techniques employing chiral stationary phases (CSPs) have been developed as powerful tools for the chiral analysis and preparation of pure enantiomers, most of which are of biological and pharmaceutical interests. Here we report our efforts in developing high-performance phenylcarbamated cyclodextrin (CD) clicked CSPs. Insights on the impact of CD functionalities in structure design are provided. High-efficiency enantioseparation of a range of aryl alcohols and flavanoids with resolution values (Rs) over 10 were demonstrated by per(3-chloro-4-methyl)phenylcarbamated CD clicked CSP. Comparison study and molecular simulations suggest the improved enantioselectivity was attributed to higher interactions energy difference between the complexes of enantiomers and CSPs with phenylcarbamated CD bearing 3-chloro and 4-methyl functionalities. PMID:26235204

  9. Searching for new antiarrhythmic agents: evaluation of meta-hydroxymexiletine enantiomers.

    PubMed

    Catalano, Alessia; Budriesi, Roberta; Bruno, Claudio; Di Mola, Antonia; Defrenza, Ivana; Cavalluzzi, Maria Maddalena; Micucci, Matteo; Carocci, Alessia; Franchini, Carlo; Lentini, Giovanni

    2013-07-01

    Mexiletine is a very well-known class IB antiarrhythmic drug, whose enantiomers differ in both pharmacodynamic and pharmacokinetic properties, the (R)-isomer being the eutomer on experimental arrhythmias and in binding studies on cardiac voltage-gated sodium channels. meta-Hydroxymexiletine (MHM) is a minor metabolite of mexiletine, which has demonstrated to be more potent than the parent compound. Herein we report the synthesis and biological evaluation of MHM enantiomers for their potential antiarrhythmic activity. The same stereoselectivity pattern observed for mexiletine was found for MHM: the (R)-enantiomer of MHM was the eutomer on ac-arrhythmia also showing a negative inotropism higher than the one displayed by mexiletine and, at the same time, a decreased vasorelaxant activity on guinea-pig left atrium and guinea-pig ileum longitudinal smooth muscle. PMID:23777871

  10. A nanoscale view of supramolecular stereochemistry in self-assembled monolayers of enantiomers and racemates.

    PubMed

    Mamdouh, Wael; Uji-I, Hiroshi; Gesquière, André; De Feyter, Steven; Amabilino, David B; Abdel-Mottaleb, Mohamed M S; Veciana, Jaume; De Schryver, Frans C

    2004-10-26

    The effect that molecular chirality has on the formation of monolayer structures by pure enantiomers and their racemates at the liquid/solid interface has been investigated for two chiral compounds (1 and 2) which differ from each other by the presence or absence of an ester function in their respective molecular structures. 1 shows pseudoracemate formation when the achiral graphite support is exposed to a solution containing a racemate while 2 shows racemic conglomerate formation. This difference is rationalized in terms of the orientation of the pure enantiomers with respect to the graphite substrate and highlights the importance of molecular structure and its influence on balancing the interplay between molecular conformation and molecular packing on the surface. For 1, nonstoichiometric mixtures of both enantiomers have been investigated, and the results are discussed in the framework of the sergeant and soldiers principle. These results are important for the understanding and prediction of spontaneous resolution in monolayer systems.

  11. Differential Binding of Rimantadine Enantiomers to Influenza A M2 Proton Channel.

    PubMed

    Wright, Anna K; Batsomboon, Paratchata; Dai, Jian; Hung, Ivan; Zhou, Huan-Xiang; Dudley, Gregory B; Cross, Timothy A

    2016-02-10

    Rimantadine hydrochloride (α-methyl-1-adamantane-methalamine hydrochloride) is a chiral compound which exerts antiviral activity against the influenza A virus by inhibiting proton conductance of the M2 ion channel. In complex with M2, rimantadine has always been characterized as a racemic mixture. Here, we report the novel enantioselective synthesis of deuterium-labeled (R)- and (S)-rimantadine and the characterization of their protein-ligand interactions using solid-state NMR. Isotropic chemical shift changes strongly support differential binding of the enantiomers to the proton channel. Position restrained simulations satisfying distance restraints from (13)C-(2)H rotational-echo double-resonance NMR show marked differences in the hydrogen-bonding pattern of the two enantiomers at the binding site. Together these results suggest a complex set of interactions between (R)-rimantadine and the M2 proton channel, leading to a higher stability for this enantiomer of the drug in the channel pore. PMID:26804976

  12. C3-symmetric Ti(IV) triphenolate amino complexes as sulfoxidation catalysts with aqueous hydrogen peroxide.

    PubMed

    Mba, Myriam; Prins, Leonard J; Licini, Giulia

    2007-01-01

    [reaction: see text] The Ti(IV) complex 2c bearing a C3-symmetric triphenolate amine ligand is an air and moisture tolerant complex that efficiently catalyzes sulfoxidation reactions at room temperature without previous activation (catalyst loading down to 0.01%, TONs up to 8000, TOFs up to 1700 h-1, quantitative yields). Reactions were performed with aqueous hydrogen peroxide as oxidant, which adds value to the methodology from the environmental viewpoint.

  13. Mutagenicity of the cysteine S-conjugate sulfoxides of trichloroethylene and tetrachloroethylene in the Ames test.

    PubMed

    Irving, Roy M; Elfarra, Adnan A

    2013-04-01

    The nephrotoxicity and nephrocarcinogenicity of trichloroethylene (TCE) and tetrachloroethylene (PCE) are believed to be mediated primarily through the cysteine S-conjugate β-lyase-dependent bioactivation of the corresponding cysteine S-conjugate metabolites S-(1,2-dichlorovinyl)-l-cysteine (DCVC) and S-(1,2,2-trichlorovinyl)-l-cysteine (TCVC), respectively. DCVC and TCVC have previously been demonstrated to be mutagenic by the Ames Salmonella mutagenicity assay, and reduction in mutagenicity was observed upon treatment with the β-lyase inhibitor aminooxyacetic acid (AOAA). Because DCVC and TCVC can also be bioactivated through sulfoxidation to yield the potent nephrotoxicants S-(1,2-dichlorovinyl)-l-cysteine sulfoxide (DCVCS) and S-(1,2,2-trichlorovinyl)-l-cysteine sulfoxide (TCVCS), respectively, the mutagenic potential of these two sulfoxides was investigated using the Ames Salmonella typhimurium TA100 mutagenicity assay. The results show both DCVCS and TCVCS were mutagenic, and TCVCS exhibited 3-fold higher mutagenicity than DCVCS. However, DCVCS and TCVCS mutagenic activity was approximately 700-fold and 30-fold lower than DCVC and TCVC, respectively. DCVC and DCVCS appeared to induce toxicity in TA100, as evidenced by increased microcolony formation and decreased mutant frequency above threshold concentrations. TCVC and TCVCS were not toxic in TA100. The toxic effects of DCVC limited the sensitivity of TA100 to DCVC mutagenic effects and rendered it difficult to investigate the effects of AOAA on DCVC mutagenic activity. Collectively, these results suggest that DCVCS and TCVCS exerted a definite but weak mutagenicity in the TA100 strain. Therefore, despite their potent nephrotoxicity, DCVCS and TCVCS are not likely to play a major role in DCVC or TCVC mutagenicity in this strain.

  14. Enantioselective synthesis of the novel chiral sulfoxide derivative as a glycogen synthase kinase 3beta inhibitor.

    PubMed

    Saitoh, Morihisa; Kunitomo, Jun; Kimura, Eiji; Yamano, Toru; Itoh, Fumio; Kori, Masakuni

    2010-09-01

    Glycogen synthase kinase 3beta (GSK-3beta) inhibitors are expected to be attractive therapeutic agents for the treatment of Alzheimer's disease (AD). Recently we discovered sulfoxides (S)-1 as a novel GSK-3beta inhibitor having in vivo efficacy. We investigated practical asymmetric preparation methods for the scale-up synthesis of (S)-1. The highly enantioselective synthesis of (S)-1 (94% ee) was achieved by titanium-mediated oxidation with D-(-)-diethyl tartrate on gram scale.

  15. Full functionalization of the imidazole scaffold by selective metalation and sulfoxide/magnesium exchange.

    PubMed

    Sämann, Christoph; Coya, Estibaliz; Knochel, Paul

    2014-01-27

    A simple, flexible, and straightforward method for the functionalization of all the positions of the imidazole heterocycle through regioselective arylations, allylations, acylations, and additions to aldehydes is disclosed. Starting from the readily available key imidazole 1, highly functionalized imidazole derivatives have been synthesized in a regioselective manner from directed metalations and a sulfoxide/magnesium exchange. Moreover, the selective N3-alkylation followed by deprotection of N1 (trans-N-alkylation) allows the regioselective N-alkylation of complex imidazoles.

  16. Determination of the impurities in drug products containing montelukast and in silico/in vitro genotoxicological assessments of sulfoxide impurity.

    PubMed

    Emerce, Esra; Cok, Ismet; Degim, I Tuncer

    2015-10-14

    Impurities affecting safety, efficacy, and quality of pharmaceuticals are of increasing concern for regulatory agencies and pharmaceutical industries, since genotoxic impurities are understood to play important role in carcinogenesis. The study aimed to analyse impurities of montelukast chronically used in asthma theraphy and perform genotoxicological assessment considering regulatory approaches. Impurities (sulfoxide, cis-isomer, Michael adducts-I&II, methylketone, methylstyrene) were quantified using RP-HPLC analysis on commercial products available in Turkish market. For sulfoxide impurity, having no toxicity data and found to be above the qualification limit, in silico mutagenicity prediction analysis, miniaturized bacterial gene mutation test, mitotic index determination and in vitro chromosomal aberration test w/wo metabolic activation system were conducted. In the analysis of different batches of 20 commercial drug products from 11 companies, only sulfoxide impurity exceeded qualification limit in pediatric tablets from 2 companies and in adult tablets from 7 companies. Leadscope and ToxTree programs predicted sulfoxide impurity as nonmutagenic. It was also found to be nonmutagenic in Ames MPF Penta I assay. Sulfoxide impurity was dose-dependent cytotoxic in human peripheral lymphocytes, however, it was found to be nongenotoxic. It was concluded that sulfoxide impurity should be considered as nonmutagenic and can be classified as ordinary impurity according to guidelines. PMID:26205398

  17. Synthesis and Antiproliferative Activities of Benzimidazole-Based Sulfide and Sulfoxide Derivatives

    PubMed Central

    Gaballah, Samir T.; El-Nezhawy, Ahmed O. H.; Amer, Hassan; Ali, Mamdouh Moawad; Mahmoud, Abeer Essam El-Din; Hofinger-Horvath, Andreas

    2016-01-01

    The design, synthesis, and in vitro antiproliferative activity of a novel series of sulfide (4a–i) and sulfoxide (5a–h) derivatives of benzimidazole, in which different aromatic and heteroaromatic acetamides are linked to benzimidazole via sulfide (4a–i) and sulfoxide (5a–h) linker, are reported and the structure-activity relationship is discussed. The new derivatives were prepared by coupling 2-(mercaptomethyl)benzimidazole with 2-bromo-N-(substituted) acetamides in dry acetone in the presence of anhydrous potassium carbonate. With very few exceptions, all of the synthesized compounds showed varying antiprolific activities against HepG2, MCF-7, and A549 cell lines. Compound 5a was very similar in potency to doxorubicin as an anticancer drug, with IC50 values 4.1 ± 0.5, 4.1 ± 0.5, and 5.0 ± 0.6 µg/mL versus 4.2 ± 0.5, 4.9 ± 0.6, and 6.1 ± 0.6 µg/mL against HepG2, MCF-7, and A549 cell lines, respectively. In contrast, none of the compounds showed activity against human prostate PC3 cancer cells. Additionally, the sulfoxide derivatives were more potent than the corresponding sulfides. PMID:27110495

  18. Studies of a novel cysteine sulfoxide lyase from Petiveria alliacea: the first heteromeric alliinase.

    PubMed

    Musah, Rabi A; He, Quan; Kubec, Roman; Jadhav, Abhijit

    2009-11-01

    A novel alliinase (EC 4.4.1.4) was detected and purified from the roots of the Amazonian medicinal plant Petiveria alliacea. The isolated enzyme is a heteropentameric glycoprotein composed of two alpha-subunits (68.1 kD each), one beta-subunit (56.0 kD), one gamma-subunit (24.8 kD), and one delta-subunit (13.9 kD). The two alpha-subunits are connected by a disulfide bridge, and both alpha- and beta-subunits are glycosylated. The enzyme has an isoelectric point of 4.78 and pH and temperature optima of 8.0 and approximately 52 degrees C, respectively. Its activation energy with its natural substrate S-benzyl-l-cysteine sulfoxide is 64.6 kJ mol(-1). Kinetic studies showed that both K(m) and V(max) vary as a function of substrate structure, with the most preferred substrates being the naturally occurring P. alliacea compounds S-benzyl-l-cysteine sulfoxide and S-2-hydroxyethyl-l-cysteine sulfoxide. The alliinase reacts with these substrates to produce S-benzyl phenylmethanethiosulfinate and S-(2-hydroxyethyl) 2-hydroxyethanethiosulfinate, respectively.

  19. Corynebacterium diphtheriae methionine sulfoxide reductase a exploits a unique mycothiol redox relay mechanism.

    PubMed

    Tossounian, Maria-Armineh; Pedre, Brandán; Wahni, Khadija; Erdogan, Huriye; Vertommen, Didier; Van Molle, Inge; Messens, Joris

    2015-05-01

    Methionine sulfoxide reductases are conserved enzymes that reduce oxidized methionines in proteins and play a pivotal role in cellular redox signaling. We have unraveled the redox relay mechanisms of methionine sulfoxide reductase A of the pathogen Corynebacterium diphtheriae (Cd-MsrA) and shown that this enzyme is coupled to two independent redox relay pathways. Steady-state kinetics combined with mass spectrometry of Cd-MsrA mutants give a view of the essential cysteine residues for catalysis. Cd-MsrA combines a nucleophilic cysteine sulfenylation reaction with an intramolecular disulfide bond cascade linked to the thioredoxin pathway. Within this cascade, the oxidative equivalents are transferred to the surface of the protein while releasing the reduced substrate. Alternatively, MsrA catalyzes methionine sulfoxide reduction linked to the mycothiol/mycoredoxin-1 pathway. After the nucleophilic cysteine sulfenylation reaction, MsrA forms a mixed disulfide with mycothiol, which is transferred via a thiol disulfide relay mechanism to a second cysteine for reduction by mycoredoxin-1. With x-ray crystallography, we visualize two essential intermediates of the thioredoxin relay mechanism and a cacodylate molecule mimicking the substrate interactions in the active site. The interplay of both redox pathways in redox signaling regulation forms the basis for further research into the oxidative stress response of this pathogen.

  20. Overexpression of methionine-R-sulfoxide reductases has no influence on fruit fly aging

    PubMed Central

    Shchedrina, Valentina A.; Vorbrüggen, Gerd; Cheon Lee, Byung; Kim, Hwa-Young; Kabil, Hadise; Harshman, Lawrence G.; Gladyshev, Vadim N.

    2009-01-01

    Methionine sulfoxide reductases (Msrs) are enzymes that repair oxidized methionine residues in proteins. This function implicated Msrs in antioxidant defense and the regulation of aging. There are two known Msr types in animals: MsrA specific for the reduction of methionine-S-sulfoxide, and MsrB that catalyzes the reduction of methionine-R-sulfoxide. In a previous study, overexpression of MsrA in the nervous system of Drosophila was found to extend lifespan by 70%. Overexpression of MsrA in yeast also extended lifespan, whereas MsrB overexpression did so only under calorie restriction conditions. The effect of MsrB overexpression on lifespan has not yet been characterized in any animal model systems. Here, the GAL4-UAS binary system was used to drive overexpression of cytosolic Drosophila MsrB and mitochondrial mouse MsrB2 in whole body, fatbody, and the nervous system of flies. In contrast to MsrA, MsrB overexpression had no consistent effect on the lifespan of fruit flies on both corn meal and sugar yeast diets. Physical activity, fecundity, and stress resistance were also similar in MsrB-overexpressing and control flies. Thus, MsrA and MsrB, the two proteins with identical function in antioxidant protein repair, have different effects on aging in fruit flies. PMID:19409408

  1. [Rapid determination of propranolol enantiomers in rat plasma by column-switching-high performance liquid chromatography].

    PubMed

    Wu, Xiaoyu; Wang, Rong; Xie, Hua; Wang, Jianfeng; Jia, Zhengping; Zhang, Qiang; Wang, Xianhua

    2011-12-01

    A high performance liquid chromatographic (HPLC) method with column-switching was developed and validated for rapid determination of two propranolol enantiomers in rat plasma. The column of restricted-access media was used as a pre-treatment column and a Chiralcel OD-RH was used as analytical column. The plasma samples were injected directly into the pretreatment column to remove plasma protein and endogenous constituents as well as to retent the propranolol enantiomers in the column using the mobile phase of borate buffer (pH 8.5)-methanol (95:5, v/v) at the flow rate of 1.0 mL/min. Then the propranolol enantiomers were transferred to the Chiralcel OD-RH column using the mobile phase of isopropanol-ethanol-0.2 mmol/L borate buffer (pH 8.5) (30: 30: 40, v/v/v) at a flow rate of 0.8 mL/min by column-switching technology. The column-switching time was 3.0 min, the used wavelength was 293 nm and the column temperature was set at 25 degrees C. The calibration curve showed excellent linear relationship (r = 0.999 5) in the concentration range from 25 mg/L to 500 mg/L for propranolol enantiomers in plasma. The intra-day and inter-day assay precisions and accuracies were well and the relative standard deviations (RSDs) were less than 5%. The average recoveries (n = 6) of the two enantiomers at 3 spiked levels were from 97.89% to 101.56%. All the values of the method validation were within the generally accepted criteria for biological sample analysis. The results show that the method is convenient, quick, sensitive and accurate. The method was successfully applied in the determination of propranolol enantiomers in rat blood pharmacokinetics study.

  2. Biological activities of α-pinene and β-pinene enantiomers.

    PubMed

    Rivas da Silva, Ana Cristina; Lopes, Paula Monteiro; Barros de Azevedo, Mariana Maria; Costa, Danielle Cristina Machado; Alviano, Celuta Sales; Alviano, Daniela Sales

    2012-05-25

    The antimicrobial activities of the isomers and enantiomers of pinene were evaluated against bacterial and fungal cells. The agar diffusion test showed that only the positive enantiomers of the α- and β-isomers of pinene were active. The minimal inhibitory concentration (MIC) and minimal microbicidal concentration (MMC) of these monoterpenes were also determined, confirming that the positive enantiomers exhibited microbicidal activity against all fungi and bacteria tested with MICs ranging from 117 to 4,150 μg/mL. However, no antimicrobial activity was detected with the negative enantiomers up to 20 mg/mL. Time-kill curves showed that (+)-α-pinene and (+)-β-pinene were highly toxic to Candida albicans, killing 100% of inoculum within 60 min. By contrast, the bactericidal effect occurred after 6 h in methicillin-resistant Staphylococcus aureus (MRSA). In combination with commercial antimicrobials, ciprofloxacin plus (+)-α-pinene or (+)-β-pinene presented synergistic activity against MRSA whereas an indifferent effect against all fungi was detected when amphotericin B was combined with the positive enantiomers of pinene. The potential of (+)-α-pinene and (+)-β-pinene to inhibit phospholipase and esterase activities was also evaluated, and the best inhibition results were obtained with Cryptococcus neoformans. C. albicans biofilm formation was prevented with the MIC concentration of (+)-α-pinene and twice the MIC value of (+)-β-pinene. Finally, the cytotoxicity of the positive enantiomers of pinene to murine macrophages was evaluated, and 250 μg/mL of (+)-α-pinene and (+)-β-pinene reduced the cell viability to 66.8% and 57.7%, respectively.

  3. Biological activities of α-pinene and β-pinene enantiomers.

    PubMed

    da Silva, Ana Cristina Rivas; Lopes, Paula Monteiro; de Azevedo, Mariana Maria Barros; Costa, Danielle Cristina Machado; Alviano, Celuta Sales; Alviano, Daniela Sales

    2012-05-25

    The antimicrobial activities of the isomers and enantiomers of pinene were evaluated against bacterial and fungal cells. The agar diffusion test showed that only the positive enantiomers of the a- and β-isomers of pinene were active. The minimal inhibitory concentration (MIC) and minimal microbicidal concentration (MMC) of these monoterpenes were also determined, confirming that the positive enantiomers exhibited microbicidal activity against all fungi and bacteria tested with MICs ranging from 117 to 4,150 µg/mL. However, no antimicrobial activity was detected with the negative enantiomers up to 20 mg/mL. Time-kill curves showed that (+)-a-pinene and (+)-β-pinene were highly toxic to Candida albicans, killing 100% of inoculum within 60 min. By contrast, the bactericidal effect occurred after 6 h in methicillin-resistant Staphylococcus aureus (MRSA). In combination with commercial antimicrobials, ciprofloxacin plus (+)-a-pinene or (+)-β-pinene presented synergistic activity against MRSA whereas an indifferent effect against all fungi was detected when amphotericin B was combined with the positive enantiomers of pinene. The potential of (+)-a-pinene and (+)-β-pinene to inhibit phospholipase and esterase activities was also evaluated, and the best inhibition results were obtained with Cryptococcus neoformans. C. albicans biofilm formation was prevented with the MIC concentration of (+)-a-pinene and twice the MIC value of (+)-β-pinene. Finally, the cytotoxicity of the positive enantiomers of pinene to murine macrophages was evaluated, and 250 µg/mL of (+)-a-pinene and (+)-β-pinene reduced the cell viability to 66.8% and 57.7%, respectively.

  4. Synthesis of the Enantiomers of Tedanalactam and the First Total Synthesis and Configurational Assignment of (+)-Piplaroxide.

    PubMed

    Romero-Ibañez, Julio; Xochicale-Santana, Leonardo; Quintero, Leticia; Fuentes, Lilia; Sartillo-Piscil, Fernando

    2016-04-22

    Highlighting the recently established methodology for the direct synthesis of glycidic amides from tertiary allyl amines, the synthesis of the enantiomers of tedanalactam were completed in two steps from the corresponding chiral dihydropiperidine. Additionally, the (+)- and (-)-enantiomers of piplaroxide were obtained from their respective tedanalactam precursor, and the absolute configuration of the naturally occurring (+)-piplaroxide was determined. The present approach represents not only the shortest synthesis of (-)-tedanalactam but also the first total synthesis of (+)-piplaroxide, a repellent against the leafcutter ant Atta cephalotes.

  5. Resolution of enantiomers of novel C2 -symmetric aminobisphosphinic acids via diastereomeric salt formation with quinine.

    PubMed

    Kaboudin, Babak; Faghihi, Mohammad Reza; Kazemi, Foad; Yokomatsu, Tsutomu

    2015-01-01

    C2 -symmetric N,N-bis(phosphinomethyl)amines were prepared by the thermal reaction of aromatic aldehydes with ammonia and hypophosphorus acid as previously described. Both enantiomers of C2 -symmetric N,N-bis(phosphinomethyl)amine were obtained in a high enantiomeric purity through the diastereomeric salt formation with (-)-quinine, and subsequent fractional crystallization. X-ray crystallographic analysis of one of the diastereomeric salts clearly revealed that (-)-quinine could be an efficient resolving agent for obtaining the single enantiomer (R,R)-N,N-bis(phosphinomethyl)amine.

  6. [Characterization of napropamide enantiomers by CD and determination of the enantiomeric ratios in water].

    PubMed

    Chen, Sheng-Wen; Cai, Xi-Yun; Xi, Meng; Zhang, An-Ping; Liu, Wei-Ping

    2006-09-01

    The enantiomers of napropamide were separated by normal phase HPLC (HPLC: high performance liquid Chromatography) with Chiralpak OJ-H column and charactered by circular dichroism. On this basis, a method for the chiral separation and micro-determination of napropamide in water was established. The linearity of calibration curve for racemic mixture was 10-100 ng x mL(-1) and the correlation coefficient was 0. 99. When 10 microL was injected, the detection limit of racemic mixture was 8 ng mL(-1), and the detection limits of both enantiomers were 4 ng x mL(-1). PMID:17112038

  7. Novel Activities of Select NSAID R-Enantiomers against Rac1 and Cdc42 GTPases.

    PubMed

    Oprea, Tudor I; Sklar, Larry A; Agola, Jacob O; Guo, Yuna; Silberberg, Melina; Roxby, Joshua; Vestling, Anna; Romero, Elsa; Surviladze, Zurab; Murray-Krezan, Cristina; Waller, Anna; Ursu, Oleg; Hudson, Laurie G; Wandinger-Ness, Angela

    2015-01-01

    Rho family GTPases (including Rac, Rho and Cdc42) collectively control cell proliferation, adhesion and migration and are of interest as functional therapeutic targets in numerous epithelial cancers. Based on high throughput screening of the Prestwick Chemical Library® and cheminformatics we identified the R-enantiomers of two approved drugs (naproxen and ketorolac) as inhibitors of Rac1 and Cdc42. The corresponding S-enantiomers are considered the active component in racemic drug formulations, acting as non-steroidal anti-inflammatory drugs (NSAIDs) with selective activity against cyclooxygenases. Here, we show that the S-enantiomers of naproxen and ketorolac are inactive against the GTPases. Additionally, more than twenty other NSAIDs lacked inhibitory action against the GTPases, establishing the selectivity of the two identified NSAIDs. R-naproxen was first identified as a lead compound and tested in parallel with its S-enantiomer and the non-chiral 6-methoxy-naphthalene acetic acid (active metabolite of nabumetone, another NSAID) as a structural series. Cheminformatics-based substructure analyses-using the rotationally constrained carboxylate in R-naproxen-led to identification of racemic [R/S] ketorolac as a suitable FDA-approved candidate. Cell based measurement of GTPase activity (in animal and human cell lines) demonstrated that the R-enantiomers specifically inhibit epidermal growth factor stimulated Rac1 and Cdc42 activation. The GTPase inhibitory effects of the R-enantiomers in cells largely mimic those of established Rac1 (NSC23766) and Cdc42 (CID2950007/ML141) specific inhibitors. Docking predicts that rotational constraints position the carboxylate moieties of the R-enantiomers to preferentially coordinate the magnesium ion, thereby destabilizing nucleotide binding to Rac1 and Cdc42. The S-enantiomers can be docked but are less favorably positioned in proximity to the magnesium. R-naproxen and R-ketorolac have potential for rapid translation and

  8. Synthesis and pharmacological characterization of beta2-adrenergic agonist enantiomers: zilpaterol.

    PubMed

    Kern, Christopher; Meyer, Thorsten; Droux, Serge; Schollmeyer, Dieter; Miculka, Christian

    2009-03-26

    The beta-adrenergic agonist 1 (zilpaterol) is used as production enhancer in cattle. Binding experiments of separated enantiomers on recombinant human beta(2)-adrenergic and mu-opioid receptors and functional studies showed that the (-)-1 enantiomer accounts for essentially all the beta(2)-adrenergic agonist activity and that it exhibits less affinity toward the mu-opioid receptor than (+)-1, which is a mu-opioid receptor antagonist. X-ray crystallography revealed the absolute configuration of (-)-1 to be 6R,7R.

  9. Novel Activities of Select NSAID R-Enantiomers against Rac1 and Cdc42 GTPases.

    PubMed

    Oprea, Tudor I; Sklar, Larry A; Agola, Jacob O; Guo, Yuna; Silberberg, Melina; Roxby, Joshua; Vestling, Anna; Romero, Elsa; Surviladze, Zurab; Murray-Krezan, Cristina; Waller, Anna; Ursu, Oleg; Hudson, Laurie G; Wandinger-Ness, Angela

    2015-01-01

    Rho family GTPases (including Rac, Rho and Cdc42) collectively control cell proliferation, adhesion and migration and are of interest as functional therapeutic targets in numerous epithelial cancers. Based on high throughput screening of the Prestwick Chemical Library® and cheminformatics we identified the R-enantiomers of two approved drugs (naproxen and ketorolac) as inhibitors of Rac1 and Cdc42. The corresponding S-enantiomers are considered the active component in racemic drug formulations, acting as non-steroidal anti-inflammatory drugs (NSAIDs) with selective activity against cyclooxygenases. Here, we show that the S-enantiomers of naproxen and ketorolac are inactive against the GTPases. Additionally, more than twenty other NSAIDs lacked inhibitory action against the GTPases, establishing the selectivity of the two identified NSAIDs. R-naproxen was first identified as a lead compound and tested in parallel with its S-enantiomer and the non-chiral 6-methoxy-naphthalene acetic acid (active metabolite of nabumetone, another NSAID) as a structural series. Cheminformatics-based substructure analyses-using the rotationally constrained carboxylate in R-naproxen-led to identification of racemic [R/S] ketorolac as a suitable FDA-approved candidate. Cell based measurement of GTPase activity (in animal and human cell lines) demonstrated that the R-enantiomers specifically inhibit epidermal growth factor stimulated Rac1 and Cdc42 activation. The GTPase inhibitory effects of the R-enantiomers in cells largely mimic those of established Rac1 (NSC23766) and Cdc42 (CID2950007/ML141) specific inhibitors. Docking predicts that rotational constraints position the carboxylate moieties of the R-enantiomers to preferentially coordinate the magnesium ion, thereby destabilizing nucleotide binding to Rac1 and Cdc42. The S-enantiomers can be docked but are less favorably positioned in proximity to the magnesium. R-naproxen and R-ketorolac have potential for rapid translation and

  10. Novel Activities of Select NSAID R-Enantiomers against Rac1 and Cdc42 GTPases

    PubMed Central

    Oprea, Tudor I.; Sklar, Larry A.; Agola, Jacob O.; Guo, Yuna; Silberberg, Melina; Roxby, Joshua; Vestling, Anna; Romero, Elsa; Surviladze, Zurab; Murray-Krezan, Cristina; Waller, Anna; Ursu, Oleg; Hudson, Laurie G.; Wandinger-Ness, Angela

    2015-01-01

    Rho family GTPases (including Rac, Rho and Cdc42) collectively control cell proliferation, adhesion and migration and are of interest as functional therapeutic targets in numerous epithelial cancers. Based on high throughput screening of the Prestwick Chemical Library® and cheminformatics we identified the R-enantiomers of two approved drugs (naproxen and ketorolac) as inhibitors of Rac1 and Cdc42. The corresponding S-enantiomers are considered the active component in racemic drug formulations, acting as non-steroidal anti-inflammatory drugs (NSAIDs) with selective activity against cyclooxygenases. Here, we show that the S-enantiomers of naproxen and ketorolac are inactive against the GTPases. Additionally, more than twenty other NSAIDs lacked inhibitory action against the GTPases, establishing the selectivity of the two identified NSAIDs. R-naproxen was first identified as a lead compound and tested in parallel with its S-enantiomer and the non-chiral 6-methoxy-naphthalene acetic acid (active metabolite of nabumetone, another NSAID) as a structural series. Cheminformatics-based substructure analyses—using the rotationally constrained carboxylate in R-naproxen—led to identification of racemic [R/S] ketorolac as a suitable FDA-approved candidate. Cell based measurement of GTPase activity (in animal and human cell lines) demonstrated that the R-enantiomers specifically inhibit epidermal growth factor stimulated Rac1 and Cdc42 activation. The GTPase inhibitory effects of the R-enantiomers in cells largely mimic those of established Rac1 (NSC23766) and Cdc42 (CID2950007/ML141) specific inhibitors. Docking predicts that rotational constraints position the carboxylate moieties of the R-enantiomers to preferentially coordinate the magnesium ion, thereby destabilizing nucleotide binding to Rac1 and Cdc42. The S-enantiomers can be docked but are less favorably positioned in proximity to the magnesium. R-naproxen and R-ketorolac have potential for rapid translation and

  11. Sobrerol enantiomers and racemates: solid-state spectroscopy, thermal behavior, and phase diagrams.

    PubMed

    Bettinetti, G; Giordano, F; Fronza, G; Italia, A; Pellegata, R; Villa, M; Ventura, P

    1990-06-01

    The characterization of the solid state of sobrerol enantiomers and racemates has been accomplished by a number of techniques on solid phase such as thermal analysis (DSC) and spectroscopy (IR, 13C NMR, and X-ray diffraction both on powders and on single crystal). Experimental and theoretical binary phase diagrams of cis- and trans-sobrerol enantiomers and their mixtures have been drawn and are discussed. Thermal analysis allowed, moreover, the detection of cis racemate polymorphism. Finally, the quantitative analysis of the cis racemate as an impurity of the trans racemate by means of microcalorimetric determinations is reported.

  12. Brain kinetics of methylphenidate (Ritalin) enantiomers after oral administration.

    PubMed

    Ding, Yu-Shin; Gatley, S John; Thanos, Panayotis K; Shea, Colleen; Garza, Victor; Xu, Youwen; Carter, Pauline; King, Payton; Warner, Don; Taintor, Nicholas B; Park, Daniel J; Pyatt, Bea; Fowler, Joanna S; Volkow, Nora D

    2004-09-01

    Methylphenidate (MP) (Ritalin) is widely used for the treatment of attention deficit hyperactivity disorder (ADHD). It is a chiral drug, marketed as the racemic mixture of d- and l-threo enantiomers. Our previous studies (PET and microdialysis) in humans, baboons, and rats confirm the notion that pharmacological specificity of MP resides predominantly in the d-isomer. A recent report that intraperitoneally (i.p.) administered l-threo-MP displayed potent, dose-dependent inhibition of cocaine- or apomorphine-induced locomotion in rats, raises the question of whether l-threo-MP has a similar effect when given orally. It has been speculated that l-threo-MP is poorly absorbed in humans when it is given orally because of rapid presystemic metabolism. To investigate whether l-threo-MP or its metabolites can be delivered to the brain when it is given orally, and whether l-threo-MP is pharmacologically active. PET and MicroPET studies were carried out in baboons and rats using orally delivered C-11-labeled d- and l-threo-MP ([methyl-(11)C]d-threo-MP and [methyl-(11)C]l-threo-MP). In addition, we assessed the effects of i.p. l-threo-MP on spontaneous and cocaine-stimulated locomotor activity in mice. There was a higher global uptake of carbon-11 in both baboon and rat brain for oral [(11)C]l-threo-MP than for oral [(11)C]d-threo-MP. Analysis of the chemical form of radioactivity in rat brain after [(11)C]d-threo-MP indicated mainly unchanged tracer, whereas with [(11)C]l-threo-MP, it was mainly a labeled metabolite. The possibility that this labeled metabolite might be [(11)C]methanol or [(11)C]CO(2), derived from demethylation, was excluded by ex vivo studies in rats. When l-threo-MP was given i.p. to mice at a dose of 3 mg/kg, it neither stimulated locomotor activity nor inhibited the increased locomotor activity due to cocaine administration. These results suggest that, in animal models, l-threo-MP or its metabolite(s) is (are) absorbed from the gastrointestinal tract and

  13. Experimental and theoretical proton affinities of methionine, methionine sulfoxide and their N- and C-terminal derivatives

    NASA Astrophysics Data System (ADS)

    Lioe, Hadi; O'Hair, Richard A. J.; Gronert, Scott; Austin, Allen; Reid, Gavin E.

    2007-11-01

    The proton affinities of methionine, methionine sulfoxide and their derivatives (methionine methyl ester, methionine sulfoxide methyl ester, methionine methyl amide, methionine sulfoxide methyl amide, N-acetyl methionine, N-acetyl methionine sulfoxide, N-acetyl methionine methyl ester, N-acetyl methionine sulfoxide methyl ester, N-acetyl methionine methyl amide and N-acetyl methionine sulfoxide methyl amide) were experimentally determined using the kinetic method, in which proton bound dimers formed via electrospray ionization (ESI) were subjected to collision induced dissociation (CID) in a triple quadrupole mass spectrometer. In addition, theoretical calculations carried out at the MP2/6-311 + G(2d,p)//B3LYP/6-31 + G(d,p) level of theory to determine the global minima of the neutral and protonated species of all derivatives studied, were used to predict theoretical proton affinities. The density function theory calculations not only support the experimental proton affinities, but also provide structural insights into the types of hydrogen bonding that stabilize the neutral and protonated methionine or methionine sulfoxide derivatives. Comparison of the proton affinities of the various methionine and methionine sulfoxide derivatives reveals that: (i) oxidation of methionine derivatives to methionine sulfoxide derivatives results in an increase in proton affinity due to higher intrinsic proton affinity and an increase in the ring size formed through charge complexation of the sulfoxide group, which allows more efficient hydrogen bonding compared to the sulfide group; (ii) C-terminal modification by methyl esterification or methyl amidation increases the proton affinity in the order of methyl amide > methyl ester > carboxylic acid due to improved charge stabilization; (iii) N-terminal modification by N-acetylation decreases proton affinity of the derivatives due to lower intrinsic proton affinity of the N-acetyl group as well as due to stabilization of the attached

  14. [Intestinal parasites in children in Biankouma, Ivory Coast (mountaineous western region): efficacy and safety of praziquantel and albendazole].

    PubMed

    Adoubryn, K D; Kouadio-Yapo, C G; Ouhon, J; Aka, N A D; Bintto, F; Assoumou, A

    2012-01-01

    Schistosomiasis and soil-transmitted helminthiasis are a global public health problem, especially among schoolchildren. The purpose of this study was to determine the overall and specific prevalences of intestinal helminth infection and to assess the clinical efficacy, tolerance, and safety of praziquantel and albendazole for treating it. A descriptive cross-sectional study based on random sampling with one degree of freedom was conducted from November 2006 to March 2007 in the primary schools of Biankouma, Côte d'Ivoire. Stool samples were collected from 386 children aged from 4 to 15 years and analyzed by direct examination, with both the simplified Ritchie and Kato techniques. Children infected by schistosomiasis and soil-transmitted helminthiasis eggs were treated with praziquantel (40 mg/kg in a single dose), albendazole (400 mg/kg in a single dose) or both, as deemed necessary. The prevalence rate of intestinal parasite infection was 55.2%, including overall 15.4% with more than one parasite: two in 14.2% and three in 1.2%. Infection was correlated with male gender and older age. The most frequent helminths were Schistosoma mansoni (35.5%) and Necator americanus (25.9%). The efficacy rate for praziquantel, defined as parasite-free stools, was 57.7% on day 14 and 80.9% on day 90. The efficacy rate for albendazole on day 7 was 96.1% for Ascaris lumbricoides, 93% for Necator americanus and 81.3% for Trichuris trichiura. Adverse effects were common (40.8%) but minor (abdominal pain, headache, and itching) within 2 to 4 hours after intake of praziquantel.

  15. Effects of albendazole on the clinical outcome and immunological responses in helminth co-infected tuberculosis patients: a double blind randomised clinical trial.

    PubMed

    Abate, E; Elias, D; Getachew, A; Alemu, S; Diro, E; Britton, S; Aseffa, A; Stendahl, O; Schön, T

    2015-02-01

    Despite several review papers and experimental studies concerning the impact of chronic helminth infection on tuberculosis in recent years, there is a scarcity of data from clinical field studies in highly endemic areas for these diseases. We believe this is the first randomised clinical trial investigating the impact of albendazole treatment on the clinical and immunological outcomes of helminth co-infected tuberculosis patients. A randomised, double-blind, placebo-controlled trial of albendazole (400mg per day for 3 days) in helminth-positive tuberculosis patients was conducted in Gondar, Ethiopia. The primary outcome was clinical improvement (ΔTB score) after 2 months. Among secondary outcomes were changes in the levels of eosinophils, CD4+ T cells, regulatory T cells, IFN-γ, IL-5 and IL-10 after 3 months. A total of 140 helminth co-infected tuberculosis patients were included with an HIV co-infection rate of 22.8%. There was no significant effect on the primary outcome (ΔTB score: 5.6±2.9 for albendazole versus 5.9±2.5 for placebo, P=0.59). The albendazole-treated group showed a decline in eosinophil cells (P=0.001) and IL-10 (P=0.017) after 3 months. In an exploratory analysis after 12 weeks, the albendazole treated group showed a trend towards weight gain compared with the placebo group (11.2±8.5 kg versus 8.2±8.7 kg, P=0.08)). The reductions in eosinophil counts and IL-10 show that asymptomatic helminth infection significantly affects host immunity during tuberculosis and can be effectively reversed by albendazole treatment. The clinical effects of helminth infection on chronic infectious diseases such as tuberculosis merit further characterisation.

  16. Combined subacute toxicity of copper and antiparasitic albendazole to the earthworm (Eisenia fetida).

    PubMed

    Gao, Yuhong; Li, Hongshuang; Li, Xuemei; Sun, Zhenjun

    2016-03-01

    Copper (Cu) is one of the most common metal contaminants, and albendazole (ABZ) is a veterinary drug with a high efficacy against helminthes. It is believed that the two may co-exist in soil. In this study, the combined subacute toxicity of Cu exposure (0, 80, 120, 160 mg kg(-1)) and ABZ exposure (0, 3, 9 mg kg(-1)) in earthworms (Eisenia fetida) were observed using three approaches, namely chronic growth and reproduction, antioxidant enzyme activity, and earthworm Cu residue. The results have shown that the toxicity of Cu on cocoon hatching success and biomass was alleviated by presence of low concentrations of ABZ (3 mg kg(-1)) during a 56-day exposure period. However, the sensitivity of the earthworms' reproduction to Cu increased with the presence of high concentrations of ABZ (9 mg kg(-1)), indicating a reduction beginning at a Cu concentration of 80 mg kg(-1), in the cocoon number, hatching success, and biomass. In addition, the three enzyme activities exhibited different responsive patterns, indicating inducement in the catalase and glutathione peroxidase, and inhibition in the superoxide dismutase, which were dependent on the exposure times and concentrations. In regard to the earthworm Cu residue, when increasing Cu exposure concentrations, the internal Cu concentrations tended to level off, exhibited a linear pattern at the Cu concentration range of 40 to 120 mg kg(-1), and showed a stable trend above 120 mg kg(-1). The results of the present study can potentially provide important information regarding the combined toxicity of the veterinary drugs and the heavy metals in soil.

  17. Combined subacute toxicity of copper and antiparasitic albendazole to the earthworm (Eisenia fetida).

    PubMed

    Gao, Yuhong; Li, Hongshuang; Li, Xuemei; Sun, Zhenjun

    2016-03-01

    Copper (Cu) is one of the most common metal contaminants, and albendazole (ABZ) is a veterinary drug with a high efficacy against helminthes. It is believed that the two may co-exist in soil. In this study, the combined subacute toxicity of Cu exposure (0, 80, 120, 160 mg kg(-1)) and ABZ exposure (0, 3, 9 mg kg(-1)) in earthworms (Eisenia fetida) were observed using three approaches, namely chronic growth and reproduction, antioxidant enzyme activity, and earthworm Cu residue. The results have shown that the toxicity of Cu on cocoon hatching success and biomass was alleviated by presence of low concentrations of ABZ (3 mg kg(-1)) during a 56-day exposure period. However, the sensitivity of the earthworms' reproduction to Cu increased with the presence of high concentrations of ABZ (9 mg kg(-1)), indicating a reduction beginning at a Cu concentration of 80 mg kg(-1), in the cocoon number, hatching success, and biomass. In addition, the three enzyme activities exhibited different responsive patterns, indicating inducement in the catalase and glutathione peroxidase, and inhibition in the superoxide dismutase, which were dependent on the exposure times and concentrations. In regard to the earthworm Cu residue, when increasing Cu exposure concentrations, the internal Cu concentrations tended to level off, exhibited a linear pattern at the Cu concentration range of 40 to 120 mg kg(-1), and showed a stable trend above 120 mg kg(-1). The results of the present study can potentially provide important information regarding the combined toxicity of the veterinary drugs and the heavy metals in soil. PMID:26780053

  18. Comparative plasma disposition kinetics of albendazole, fenbendazole, oxfendazole and their metabolites in adult sheep.

    PubMed

    Lanusse, C E; Gascon, L H; Prichard, R K

    1995-06-01

    The comparative plasma disposition kinetics of albendazole (ABZ), fenbendazole (FBZ) and oxfendazole (OFZ) following their oral administration (5 mg/kg) to adult sheep was characterized. Jugular blood samples were taken serially over a 144 h period and plasma was analysed by high performance liquid chromatography (HPLC) for ABZ, ABZ sulphoxide (ABZSO) and ABZ sulphone (ABZSO2) (ABZ treatment), and for FBZ, OFZ and FBZ sulphone (FBZSO2) (FBZ and OFZ treatments). While the ABZ parent drug was not detected at any time post-treatment, ABZSO and ABZSO2 were the analytes recovered in plasma after oral administration of ABZ to sheep. The active ABZSO metabolite was the main analyte recovered in plasma (between 0.25 and 60 h post-treatment), accounting for 71% of the total AUC. FBZ, OFZ and FBZSO2 were the analytes detected in plasma following the oral administration of both FBZ and OFZ to sheep. Low concentrations of FBZ were found in plasma between 4 (FBZ treatment) or 8 h (OFZ treatment) and 72 h post-treatment. The plasma profile of each analyte followed a similar pattern after both treatments; OFZ being the main component detected in plasma. The plasma disposition of ABZ metabolites was markedly different to that of FBZ derivatives. ABZSO exhibited faster absorption and a higher Cmax than OFZ (both treatments). Furthermore, while ABZSO declined relatively rapidly in plasma reaching non-detectable concentrations at 60 h post-ABZ administration, OFZ was found in plasma for up to 120 (FBZ treatment) and 144 h (OFZ treatment).(ABSTRACT TRUNCATED AT 250 WORDS)

  19. An antioxidant response is involved in resistance of Giardia duodenalis to albendazole

    PubMed Central

    Argüello-García, Raúl; Cruz-Soto, Maricela; González-Trejo, Rolando; Paz-Maldonado, Luz María T.; Bazán-Tejeda, M. Luisa; Mendoza-Hernández, Guillermo; Ortega-Pierres, Guadalupe

    2015-01-01

    Albendazole (ABZ) is a therapeutic benzimidazole used to treat giardiasis that targets β-tubulin. However, the molecular bases of ABZ resistance in Giardia duodenalis are not understood because β-tubulin in ABZ-resistant clones lacks mutations explaining drug resistance. In previous work we compared ABZ-resistant (1.35, 8, and 250 μM) and ABZ-susceptible clones by proteomic analysis and eight proteins involved in energy metabolism, cytoskeleton dynamics, and antioxidant response were found as differentially expressed among the clones. Since ABZ is converted into sulphoxide (ABZ-SO) and sulphone (ABZ-SOO) metabolites we measured the levels of these metabolites, the antioxidant enzymes and free thiols in the susceptible and resistant clones. Production of reactive oxygen species (ROS) and levels of ABZ-SO/ABZ-SOO induced by ABZ were determined by fluorescein diacetate-based fluorescence and liquid chromatography respectively. The mRNA and protein levels of antioxidant enzymes (NADH oxidase, peroxiredoxin 1a, superoxide dismutase and flavodiiron protein) in these clones were determined by RT-PCR and proteomic analysis. The intracellular sulfhydryl (R-SH) pool was quantified using dinitrobenzoic acid. The results showed that ABZ induced ROS accumulation in the ABZ-susceptible Giardia cultures but not in the resistant ones whilst the accumulation of ABZ-SO and ABZ-SOO was lower in all ABZ-resistant cultures. Consistent with these findings, all the antioxidant enzymes detected and analyzed were upregulated in ABZ-resistant clones. Likewise the R-SH pool increased concomitantly to the degree of ABZ-resistance. These results indicate an association between accumulation of ABZ metabolites and a pro-oxidant effect of ABZ in Giardia-susceptible clones. Furthermore the antioxidant response involving ROS-metabolizing enzymes and intracellular free thiols in ABZ-resistant parasites suggest that this response may contribute to overcome the pro-oxidant cytotoxicity of ABZ. PMID

  20. Correlation and in vitro studies on radioactive and nonradioactive albendazole-beta-cyclodextrin complex tablets.

    PubMed

    Cetin, E O; Ilem, D; Gundogdu, E; Asikoglu, M; Kirilmaz, L

    2011-09-01

    The work aims to confirm the complexation of albendazole (ABZ) by beta-cyclodextrin (beta-CD), and to compare them with pure ABZ tablets using radioactive and nonradioactive dissolution studies. The complex tablets were prepared by kneading a binary mixture of ABZ and beta-CD and a direct compression method. Nuclear magnetic resonance (NMR) spectroscopy, scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy were examined to prove the formation of complexes in the final products. The radiolabelled tablets were labelled with 99mTc-DTPA. Dissolution studies were performed with radiolabelled and nonradiolabelled tablets in two dissolution media (pH 1.2 and pH 7.4). The tablets were added to an acidic solution (pH = 1.2) to quantify the concentration of the drug inside the beta-CD cavity. The other medium (pH = 7.4) was used to prove the existence of non-complexed drug in each powder, as the drug's solubility increases with pH. It was observed that complexation occurred in all tablets, and beta-cyclodextrin (beta-CD) could increase the aqueous solubility. Further, a correlation was shown between dissolution results for radiolabelled and nonradiolabelled tablets. This study shows that the characterization studies were a good indicator for the ABZ: beta-CD complex. According to the phase solubility studies, the solubility of ABZ increased when the amount of beta-CD increased, and drug release from tablets in pH 7.4 and pH 1.2 media was dramatically improved by the addition of beta-CD compared with the pure ABZ tablet. PMID:22026122

  1. Albendazole induces oxidative stress and DNA damage in the parasitic protozoan Giardia duodenalis

    PubMed Central

    Martínez-Espinosa, Rodrigo; Argüello-García, Raúl; Saavedra, Emma; Ortega-Pierres, Guadalupe

    2015-01-01

    The control of Giardia duodenalis infections is carried out mainly by drugs, among these albendazole (ABZ) is commonly used. Although the cytotoxic effect of ABZ usually involves binding to β-tubulin, it has been suggested that oxidative stress may also play a role in its parasiticidal mechanism. In this work the effect of ABZ in Giardia clones that are susceptible or resistant to different concentrations (1.35, 8, and 250 μM) of this drug was analyzed. Reactive oxygen species (ROS) were induced by ABZ in susceptible clones and this was associated with a decrease in growth that was alleviated by cysteine supplementation. Remarkably, ABZ-resistant clones exhibited partial cross-resistance to H2O2, whereas a Giardia H2O2-resistant strain can grow in the presence of ABZ. Lipid oxidation and protein carbonylation in ABZ-treated parasites did not show significant differences as compared to untreated parasites; however, ABZ induced the formation of 8OHdG adducts and DNA degradation, indicating nucleic acid oxidative damage. This was supported by observations of histone H2AX phosphorylation in ABZ-susceptible trophozoites treated with 250 μM ABZ. Flow cytometry analysis showed that ABZ partially arrested cell cycle in drug-susceptible clones at G2/M phase at the expense of cells in G1 phase. Also, ABZ treatment resulted in phosphatidylserine exposure on the parasite surface, an event related to apoptosis. All together these data suggest that ROS induced by ABZ affect Giardia genetic material through oxidative stress mechanisms and subsequent induction of apoptotic-like events. PMID:26300866

  2. Thrombocytopenia caused by albendazole in a patient with Sjögren’s syndrome: A case report

    PubMed Central

    Açıkgöz, Pınar; Türkbeyler, İbrahim Halil; Pehlivan, Yavuz

    2014-01-01

    Sjögren’s syndrome (SS) is an autoimmune disease characterised by a chronic inflammatory response mainly localised to the lachrymal and salivary glands. Haematological abnormalities are common, although they rarely have clinical significance. Here, we report a patient with SS and thrombocytopenia caused by albendazole. Haematological abnormalities such as thrombocytopenia are seen in approximately 5–15% of SS patients; however, this disease is usually asymptomatic and can often be recovered to normal levels with corticosteroids. If it is not, we should keep in mind other reasons for the thrombocytopenia, such as drug use.

  3. Investigation of racemisation of the enantiomers of glitazone drug compounds at different pH using chiral HPLC and chiral CE.

    PubMed

    Jamali, Babak; Bjørnsdottir, Inga; Nordfang, Ole; Hansen, Steen Honoré

    2008-01-01

    Drug enantiomers can have biologically distinct interactions within the biological system and consequently different pharmacological or toxicological effects. Development of a better and safer drug product may be considered if one of the enantiomers has a significantly better effect/side effect ratio than the other. Investigation of the single enantiomers in a racemic mixture could be valuable in order to investigate whether the single enantiomers demonstrate difference in pharmacological effect and/or fewer side effects versus the racemic mixture. In this context investigation of a possible racemisation of the pure enantiomers is very important. In order to obtain the enantiomers of the racemic pioglitazone and the racemic rosiglitazone an HPLC method for chiral separation was developed. Using this method the R and S enantiomers were separated and the method was used to collect each enantiomer for investigation of racemisation process. The racemisation of the enantiomers of pioglitazone and rosiglitazone was investigated at pH 2.5, 7.4 and 9.3 using a chiral CE system. At pH 2.5 all enantiomers showed a slow racemisation. After 192 h (8 days) at 37 degrees C the ratio of the enantiomers in the mixture for all four isolated enantiomers was approximately 2 to 1 and after 1440 h (30 days) full racemisation was observed. The racemisation speed increased with increasing pH. At pH 7.4 the ratio of the enantiomers in the mixtures was approximately 2 to 1 already after 10h. Full racemisation was observed within 48 h (2 days) at pH 7.4 and within 24 h at pH 9.3. These investigations have shown that it is possible to separate and isolate the enantiomers from a racemic mixture of glitazone drug substance and perform racemisation studies on each enantiomer. PMID:17942259

  4. Differential Toxicity and Accumulation of Fipronil Enantiomers in the Fathead Minnow (Pimephales promelas)

    EPA Science Inventory

    Fipronil is a chiral insecticide applied as a racemate of two enantiomers. Because of its high log Koc, fipronil will be found primarily in sediments of aquatic environments. Although a number of studies have examined toxicity in aquatic invertebrates, data on enantioselective t...

  5. Effect of pressure on the chromatographic separation of enantiomers under reversed-phase conditions.

    PubMed

    Makarov, Alexey A; Regalado, Erik L; Welch, Christopher J; Schafer, Wes A

    2014-07-25

    Commercially available ultra high pressure liquid chromatography (UHPLC) equipment offers the ability to explore the influence of backpressure on chromatographic separations. However, the influence of pressure on the chromatographic separation of enantiomers on chiral stationary phases remains largely unexplored. In this investigation we surveyed the effects of pressure on the separation of enantiomers using several reversed-phase chiral stationary phases. The experiments were conducted at constant flow rate and column temperature, using isocratic conditions. The only variable parameter was pressure, which was adjusted using a post-column backpressure regulator. For the separation of enantiomers on chiral stationary phases, an increase in pressure from approximately 2,000 psi (138 bar) to approximately 8,000 psi (552 bar) at constant flow rate and temperature led to an increase of retention factors for some analytes and a decrease for others. Achiral separations on a C-18 stationary phase always led only to an increase of retention factor. Interestingly, changes in pressure led to small changes in enantioselectivity during reversed-phase chiral separation of enantiomers, suggesting that such studies may be of value for better understanding the mechanisms underlying chromatographic enantioseparation.

  6. Enantioselective Separation of 4,8-DHT and Phytotoxicity of the Enantiomers on Various Plant Species.

    PubMed

    Yang, Li; Ma, Xiao-Yan; Ruan, Xiao; Jiang, De-An; Pan, Cun-De; Wang, Qiang

    2016-01-01

    As a candidate for bioherbicide, 4,8-dihydroxy-1-tetralone (4,8-DHT) was isolated from Caryospora callicarpa epicarp and its two enantiomers, S-(+)-isosclerone and R-(-)-regiolone, were separated by chiral high-performance liquid chromatography (HPLC) on a Chiralcel OD column with chiral stationary phase (CSP)-coated cellulose-tris(3,5-dimethylphenylcarbamate). Then, the phytotoxicity of 4,8-DHT and its enantiomers toward the seeds germination and seedling growth of the five tested plant species, including lettuce (Latuca sativa), radish (Raphanus sativus), cucumber (Cucumis sativus), onion (Allium cepa), and wheat (Triticum aestivum), were investigated and the results indicated a hormesis at low concentration of 4,8-DHT and its enantiomers, but a retardant effect at high concentration. Between the two enantiomers of 4,8-DHT, the S-(+)-isosclerone was more toxic to seeds germination and seedling growth of the five tested plant species than the R-(-)-regiolone, and also the phytotoxicity of S-(+)-isosclerone varied with different plants. For example, S-(+)-isosclerone was the most active to seedling growth of lettuce, indicating that S-(+)-isosclerone had specific effects on different organisms. Thus, all of the chirality and concentration of 4,8-DHT, as well as the affected plant species, need to be taken into consideration in the development and utilization of 4,8-DHT. PMID:27110760

  7. Crystalline stereocomplexed polycarbonates: hydrogen-bond-driven interlocked orderly assembly of the opposite enantiomers.

    PubMed

    Liu, Ye; Ren, Wei-Min; Wang, Meng; Liu, Chuang; Lu, Xiao-Bing

    2015-02-01

    Four novel crystalline stereocomplexed polymers are formed by mixing isotactic (R)- and (S)-polycarbonates in 1:1 mass ratio. They show the enhanced thermal stability and new crystalline behavior, significantly distinct from the component enantiomer. Two stereocomplexed CO2 -based polycarbonates from meso-3,4-epoxytetrahydrofuran and 4,4-dimethyl-3,5,8-trioxabicyclo[5.1.0]octane have high melting temperatures of up to 300 °C, about 30 °C higher than the individual enantiomers. Isotactic (R)- or (S)-poly(cyclopentene carbonate) and poly(cis-2,3-butene carbonate) are typical amorphous polymeric materials, however, upon mixing both enantiomers together, a strong interlocked interaction between polymer chains of opposite configuration occurs, affording the crystalline stereocomplexes with melting temperatures of about 200 °C and 180 °C, respectively. A DFT study suggests that the driving force forming the stereocomplex is the hydrogen-bonding between carbonate units of the opposite enantiomers. PMID:25537626

  8. Experiment and modeling for the separation of guaifenesin enantiomers using simulated moving bed and Varicol units.

    PubMed

    Gong, Rujin; Lin, Xiaojian; Li, Ping; Yu, Jianguo; Rodrigues, Alirio E

    2014-10-10

    The separation of guaifenesin enantiomers by both simulated moving bed (SMB) process and Varicol process was investigated experimentally and theoretically, where the columns were packed with cellulose tris 3,5-dimethylphenylcarbamate (Chiralcel OD) stationary phase and a mixture of n-hexane and ethanol was used as mobile phase. The operation conditions were designed based on the separation region with the consideration of mass transfer resistance and axial dispersion, and the experiments to separate guaifenesin enantiomers were carried out on VARICOL-Micro unit using SMB process with the column configuration of 1/2/2/1 and Varicol process with the column configuration of 1/1.5/1.5/1, respectively. Single enantiomer with more than 99.0% purity was obtained in both processes with the productivity of 0.42 genantiomer/dcm(3) CSP for SMB process and 054 genantiomer/dcm(3) CSP for Varicol process. These experimental results obtained from SMB and Varicol processes were compared with those reported from literatures. In addition, according to the numerical simulation, the effects of solid-film mass transfer resistance and axial dispersion on the internal profiles were discussed, and the effect of column configuration on the separation performance of SMB and Varicol processes was analyzed for a few columns system. The feasibility and efficiency for the separation of guaifenesin enantiomers by SMB and Varicol processes were evaluated. PMID:25047823

  9. Enantiomer excesses of rare and common sugar derivatives in carbonaceous meteorites

    NASA Astrophysics Data System (ADS)

    Cooper, George; Rios, Andro C.

    2016-06-01

    Biological polymers such as nucleic acids and proteins are constructed of only one—the d or l—of the two possible nonsuperimposable mirror images (enantiomers) of selected organic compounds. However, before the advent of life, it is generally assumed that chemical reactions produced 50:50 (racemic) mixtures of enantiomers, as evidenced by common abiotic laboratory syntheses. Carbonaceous meteorites contain clues to prebiotic chemistry because they preserve a record of some of the Solar System’s earliest (˜4.5 Gy) chemical and physical processes. In multiple carbonaceous meteorites, we show that both rare and common sugar monoacids (aldonic acids) contain significant excesses of the d enantiomer, whereas other (comparable) sugar acids and sugar alcohols are racemic. Although the proposed origins of such excesses are still tentative, the findings imply that meteoritic compounds and/or the processes that operated on meteoritic precursors may have played an ancient role in the enantiomer composition of life’s carbohydrate-related biopolymers.

  10. Unequal Activities of Enantiomers via Biological Receptors: Examples of Chiral Drug, Pesticide, and Fragrance Molecules

    ERIC Educational Resources Information Center

    Mannschreck, Albrecht; Kiesswetter, Roland; von Angerer, Erwin

    2007-01-01

    A molecule coming from outside an organism can form a ligand-receptor complex. Upon its formation, a message is transmitted, for example, to certain cells. In this way, two enantiomers can emit messages that differ, either quantitatively or qualitatively. In the present article, these facts are taken as a common basis for the actions of chiral…

  11. Enantiomer Specific Measurements of Current-Use Pesticides in Aquatic Systems.

    EPA Science Inventory

    Research has shown that current-use pesticides can enter urban and agricultural watersheds and adversely affect aquatic organisms. A potential cause may be higher concentrations of the more toxic pesticide enantiomer present in the pesticide mixture. The presence of pesticide ena...

  12. Enantioselective Separation of 4,8-DHT and Phytotoxicity of the Enantiomers on Various Plant Species.

    PubMed

    Yang, Li; Ma, Xiao-Yan; Ruan, Xiao; Jiang, De-An; Pan, Cun-De; Wang, Qiang

    2016-04-22

    As a candidate for bioherbicide, 4,8-dihydroxy-1-tetralone (4,8-DHT) was isolated from Caryospora callicarpa epicarp and its two enantiomers, S-(+)-isosclerone and R-(-)-regiolone, were separated by chiral high-performance liquid chromatography (HPLC) on a Chiralcel OD column with chiral stationary phase (CSP)-coated cellulose-tris(3,5-dimethylphenylcarbamate). Then, the phytotoxicity of 4,8-DHT and its enantiomers toward the seeds germination and seedling growth of the five tested plant species, including lettuce (Latuca sativa), radish (Raphanus sativus), cucumber (Cucumis sativus), onion (Allium cepa), and wheat (Triticum aestivum), were investigated and the results indicated a hormesis at low concentration of 4,8-DHT and its enantiomers, but a retardant effect at high concentration. Between the two enantiomers of 4,8-DHT, the S-(+)-isosclerone was more toxic to seeds germination and seedling growth of the five tested plant species than the R-(-)-regiolone, and also the phytotoxicity of S-(+)-isosclerone varied with different plants. For example, S-(+)-isosclerone was the most active to seedling growth of lettuce, indicating that S-(+)-isosclerone had specific effects on different organisms. Thus, all of the chirality and concentration of 4,8-DHT, as well as the affected plant species, need to be taken into consideration in the development and utilization of 4,8-DHT.

  13. ACUTE AND CHRONIC EFFECTS OF FIPRONIL AND ITS ENANTIOMERS TO AQUATIC ORGANISMS

    EPA Science Inventory

    Fipronil is a phenylpyrazole insecticide used in agriculture and domestic settings for controlling various insect pests in crops, lawns and residential structures. Fipronil is chiral; however, it is released into the environment as a racemic mixture of two enantiomers. In this st...

  14. TOXICITY OF FIPRONIL AND ITS ENANTIOMERS TO MARINE AND FRESHWATER NON-TARGETS

    EPA Science Inventory

    Fipronil is a phenylpyrazole insecticide used in agricultural and domestic settings for controlling various insect pests in crops, lawns, and residential structures. Fipronil is chiral; however, it is released into the environment as a racemic mixture of two enantiomers. In this ...

  15. #2) Enantiomer Specific Measurements of Current-use Pesticides in Aquatic Systems

    EPA Science Inventory

    Research has shown that current-use pesticides can enter urban and agricultural watersheds and adversely affect aquatic organisms. A potential cause may be higher concentrations of the more toxic pesticide enantiomer present in the pesticide mixture. The presence of pesticide ena...

  16. Discovery of a solid solution of enantiomers in a racemate-forming system by seeding.

    PubMed

    Huang, Jun; Chen, Shuang; Guzei, Ilia A; Yu, Lian

    2006-09-13

    A racemic liquid of opposite enantiomers usually crystallizes as a racemic compound (racemate), rarely as a conglomerate, and even more rarely as a solid solution. We discovered a Type II solid solution (mixed crystal) of the enantiomers of the chiral drug tazofelone (TZF) by seeding its racemic liquid with enantiomerically pure crystals (enantiomorphs). Without seeding, the racemic liquid crystallized as a racemic compound. The crystal structure of this solid solution resembles that of the enantiomorph but has static disorder arising from the random substitution of enantiomers. This solid solution is a kinetic product of crystallization made possible by its faster growth rate compared to that of the competing racemate (by 4- to 40-fold between 80 and 146 degrees C). The free energy of the solid solution continuously varies with the enantiomeric composition between those of the conglomerate and the racemates. The existence of the TZF solid solution explains the absence of eutectic melting between crystals of different enantiomeric compositions. The ability of TZF to simultaneously form racemate and solid solution originates from its conformational flexibility. Similar solid solutions of enantiomers may exist in other systems and may be discovered in similar ways. The study demonstrates the use of cross-nucleation for discovering and engineering crystalline materials to optimize physical properties.

  17. Enantioselective HPLC determination of oxiracetam enantiomers and application to a pharmacokinetic study in beagle dogs.

    PubMed

    Zhang, Qiuyang; Yang, Wei; Zhang, Qing; Yang, Yue; Li, Junxiu; Lu, Yang; Zheng, Yi; He, Jiake; Zhao, Di; Chen, Xijing

    2015-07-01

    An enantioselective high-performance liquid chromatography method was developed and validated for the determination of oxiracetam enantiomers, a cognition and memory enhancer, in beagle dog plasma. The plasma samples were prepared by methanol extraction from 200μL plasma, and then the baseline resolution was achieved on a Chiralpak ID column (250mm×4.6mm, 5μm) with mobile phase of hexane-ethanol-trifluoroacetic acid (78:22:0.1, v/v/v) at flow rate of 1.0mL/min. The column elute was monitored using ultraviolet detection at 214nm. The method was linear over concentration range 0.50-100μg/mL for both enantiomers. The relative standard deviation values for intra- and inter-day precision were 0.78-13.61 and 0.74-8.92% for (R)- and (S)-oxiracetam, respectively. The relative error values of accuracy ranged from -4.74 to 10.48% for (R)-oxiracetam and from -0.19 to 11.48% for (S)-oxiracetam. The method was successfully applied to a pharmacokinetic study of individual enantiomer and racemic oxiracetam in beagle dogs after oral administration. The disposition of the two enantiomers was not stereoselective and chiral inversion was not observed in beagle dogs. The pharmacokinetic profiles of (S)-oxiracetam were similar with racemic oxiracetam in beagle dogs.

  18. Bioaccumulation and excretion of enantiomers of myclobutanil in Tenebrio molitor larvae through dietary exposure.

    PubMed

    Lv, Xiaotian; Liu, Chen; Li, Yaobin; Gao, Yongxin; Guo, Baoyuan; Wang, Huili; Li, Jianzhong

    2013-12-01

    The bioaccumulation and excretion of enantiomers of myclobutanil in Tenebrio molitor larvae through dietary exposure under laboratory conditions were investigated using high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) based on a ChiralcelOD-3R [cellulosetris-tris-(3, 5-dichlorophenyl-carbamate)] column. The wheat bran fed to Tenebrio molitor larvae was spiked with racemic myclobutanil at two dose levels of 20 mg/kg and 2 mg/kg (dry weight). The results showed that there was a significant trend of enantioselective bioaccumulation in the larvae with a preferential accumulation of (-)-myclobutanil in 20 mg/kg dose exposure, but it was not obviously observed in the 2 mg/kg dose group. A kinetic model considering enantiomerization between the two enantiomers based on first-order reactions was built and the rate constants were estimated to discuss the kinetic reason for the different concentrations of individual enantiomers in the larvae. The approximations implied an inversion between the two enantiomers with a relatively higher rate of the inversion from (-)-myclobutanil to (+)-myclobutanil. Meanwhile, analysis of data of excretion samples suggested the active excretion is probably an important pathway for the insect to eliminate myclobutanil rapidly with nonenantioselectivity as a passive transport process, which was consistent with the low accumulation efficiency of myclobutanil measured by BAF (bioaccumulation factor).

  19. Asymmetric chemoenzymatic synthesis of miconazole and econazole enantiomers. The importance of chirality in their biological evaluation.

    PubMed

    Mangas-Sánchez, Juan; Busto, Eduardo; Gotor-Fernández, Vicente; Malpartida, Francisco; Gotor, Vicente

    2011-04-01

    A simple and novel chemoenzymatic route has been applied for the first time in the synthesis of miconazole and econazole single enantiomers. Lipases and oxidoreductases have been tested in stereoselective processes; the best results were attained with oxidoreductases for the introduction of chirality in an adequate intermediate. The behaviors of a series of ketones and racemic alcohols in bioreductions and acetylation procedures, respectively, have been investigated; the best results were found with alcohol dehydrogenases A and T, which allowed the production of (R)-2-chloro-1-(2,4-dichlorophenyl)ethanol in enantiopure form under very mild reaction conditions. Final chemical modifications have been performed in order to isolate the target fungicides miconazole and econazole both as racemates and as single enantiomers. Biological evaluation of the racemates and single enantiomers has shown remarkable differences against the growth of several microorganisms; while (R)-miconazole seemed to account for most of the biological activity of racemic miconazole on all the strains tested, both enantiomers of econazole showed considerable biological activities. In this manner, (R)-econazole showed higher values against Candida krusei , while higher values were observed for (S)-econazole against Cryptococcus neoformans, Penicillium chrysogenum, and Aspergillus niger.

  20. Enantiomer Specific Measurements of Current-use Pesticides in Aquatic Systems (#2)

    EPA Science Inventory

    Research has shown that current-use pesticides can enter urban and agricultural watersheds and adversely affect aquatic organisms. A potential cause may be higher concentrations of the more toxic pesticide enantiomer present in the pesticide mixture. The presence of pesticide ena...

  1. Sodium-dependent inhibition by PN200-110 enantiomers of nicotinic adrenal catecholamine release.

    PubMed Central

    Cárdenas, A. M.; Montiel, C.; Artalejo, A. R.; Sánchez-García, P.; García, A. G.

    1988-01-01

    1. Dimethylphenylpiperazinium (DMPP) or high K concentrations evoke catecholamine release from perfused cat adrenal glands; in both cases the secretory response was significantly enhanced in the absence of Na. Tetrodotoxin did not modify the nicotinic secretory response. 2. The (+)- and (-)-enantiomers of the dihydropyridine Ca channel blocker PN200-110 show a high degree of stereoselectivity in the inhibition of catecholamine secretion evoked by high K or by DMPP in the presence of Na, the (+)-enantiomer being 57 and 80 times more potent, respectively, than the (-)-enantiomer. Both, noradrenaline and adrenaline release were equally depressed by PN200-110. 3. The IC50 values for (+)- and (-)-PN200-110 for blockade of the secretory response induced by K or DMPP in the presence of Na are in the same range. In the absence of Na, (-)-PN200-110 did not affect DMPP-evoked secretion; however, the (+)-enantiomer partially inhibited it. 4. The results suggest that the physiological catecholamine release from chromaffin cells is preceded by Na entry through the nicotinic receptor-associated ionophore; this causes cell depolarization, opening of voltage-dependent, dihydropyridine-sensitive Ca channels and Ca entry into the cell. In the absence of Na, additional Ca influx through an alternative pathway (the nicotinic cholinoceptor ionophore?) might also activate secretion. PMID:2975522

  2. Determination of S- and R-warfarin enantiomers by using modified HPLC method.

    PubMed

    Qayyum, Aisha; Najmi, Muzammil Hasan; Khan, Abdul Muqeet; Abbas, Mateen; Naveed, Abdul Khaliq; Jameel, Ahsan

    2015-07-01

    Warfarin is a commonly prescribed anticoagulant existing in two enantiomeric forms S- and R-warfarin. Many techniques have been used to analyze warfarin in plasma but less frequently for enantiomeric analysis. One of the HPLC method employed was further simplified and made economical. Method was validated according to ICH guidelines and was found to be sensitive, reliable and less time consuming. For both enantiomers, LLOQ was 12.5 ng/mL. The CV% and accuracy for method were in the range of 0.8-14.6% and 92-107% respectively. The recoveries for both enantiomers were in the range of 86-103.8%. Blood samples were collected from 170 stable patients taking warfarin and S- and R-warfarin levels were determined by this method. Majority of subjects were found to have S/R-warfarin ratio of about 1:2 as reported in previous studies due to rapid clearance of S-enantiomer than R-enantiomer. However individual subjects data was suggestive of presence of slow metabolizers of S-warfarin leading to altered S/R ratio. Previous studies have also pointed out CYP2C9 polymorphism being responsible for such inter-individual differences in S-warfarin metabolism. So plasma warfarin S/R ratio may serve as a useful phenotypic test for CYP2C9 polymorphism.

  3. ANALYSIS AND FATE OF ENANTIOMERS OF PESTICIDES AND OTHER ENVIRONMENTAL POLLUTANTS

    EPA Science Inventory

    Up to 25% of pesticides and other environmental pollutants are chiral and exist as sets of mirror image isomers, or enantiomers, that usually differ in their microbiological transformation rates and toxicities. To provide for more accurate risk assessment of these chiral pollutan...

  4. Composition of Gossypol Enantiomers in Seeds of Uzbek Industrial Cotton Species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The total gossypol percentage and the composition of gossypol enantiomers was determined in seeds of 26 varieties of Gossypium hirsutum cotton and two varieties of G. barbadense cotton that are cultivated in Uzbekistan by reverse-phase HPLC. The percentage of the more highly toxic (-)-gossypol form...

  5. Synthesis of both enantiomers of 12-methyl-13-tridecanolide and 14-methyl-15-pentadecanolide (muscolide).

    PubMed

    Noda, Yoshihiro; Mamiya, Natsuki; Kashin, Hitoshi

    2013-07-01

    Both enantiomers of 12-methyl-13-tridecanolide{(R)-(+)-1, (S)-(-)-1} and 14-methyl-15-pentadecanolide (muscolide) {(R)-(+)-2, (S)-(-)-2} were synthesized from either (S)-(+)- or (R)-(-)-3-bromo-2-methyl-1-propanol 8 as a chiral building block. PMID:23980425

  6. Locally designed pulse shaping for selective preparation of enantiomers from their racemate

    NASA Astrophysics Data System (ADS)

    Hoki, K.; Ohtsuki, Y.; Fujimura, Y.

    2001-01-01

    We present a method for the design of laser fields to control a selective preparation of enantiomers from their racemate. An expression for two components of the laser pulses [EX(t) and EY(t)] propagating along the Z axis is derived using a locally optimized control theory in the density operator formalism. This expression was applied to a selective preparation of (R-, L-) enantiomers from preoriented phosphinotioic acid (H2POSH) at low temperatures. The target operator was set for the populations to be localized in one side of the double-well potential. First, a simple one-dimensional model was treated. Then, a two-dimensional model in which a free rotation around the preoriented torsional axis is included was briefly considered. In the one-dimensional model, almost complete preparation of the enantiomers was obtained. The optimal electric field consists of a sequence of two linearly polarized pulses with the same phases but with different magnitudes. This means that the resultant electric field is linearly polarized with the polarization for obtaining the R-form nearly parallel to its S-H bond. The optimal electric field transfers the L-form into the R-form while suppressing the reverse process. In the two-dimensional model, the enantiomer selective preparation is controlled by a sequence of circularly polarized pulses.

  7. THE IN VITRO PHASE I METABOLISM OF THE TRIAZOLE FUNGICIDE BROMUCONAZOLE AND ITS FOUR ENANTIOMERS

    EPA Science Inventory

    The triazole fungicide bromuconazole contains two chiral centers and exists as two diastereomers, each with two enantiomers. It has been widely used as a mixture of its diastereomers on food products. Here we report on the in vitro metabolism of the individual and combined dias...

  8. Stereoselective effects of mexiletine enantiomers on sodium currents and excitability characteristics of adult skeletal muscle fibers.

    PubMed

    De Luca, A; Natuzzi, F; Lentini, G; Franchini, C; Tortorella, V; Conte Camerino, D

    1995-12-01

    The effects of the enantiomers of mexiletine were tested on sodium currents of frog skeletal muscle fibers recorded by means of the three vaseline gap voltage clamp method and compared with the effects produced by tocainide enantiomers. The R-(-) mexiletine produced a tonic block of the sodium current, elicited by single depolarizing test pulses from the holding potential of -100 mV to -20 mV, with an IC50 of 43.9 +/- 1 microM, whereas the corresponding S-(+) enantiomer produced the same effects at about twofold higher concentrations. A similar steroselectivity was observed with tocainide enantiomers, but at about 5 fold higher concentrations. Both the R-(-) and S-(+) enantiomers of mexiletine and tocainide produced a further use-dependent block of sodium currents when the test pulse was applied repetitively at a frequency of 2 Hz. The use dependent behavior led to a significant lowering of the IC50 values with respect to the tonic block but the eudismic ratios ([IC50S-(+)]/[IC50R(-)]) and the relative potency between mexiletine and tocainide were maintained. All the tested compounds produced a left shift of the steady state inactivation curves (h infinity), suggesting a high-affinity interaction with the inactivated sodium channels. Again a stronger potency of R-(-) vs. S-(+) enantiomers and of mexiletine vs. tocainide was observed. The excitability characteristics recorded from the semitendinosus muscle by the two microelectrode technique were modified by the tested drugs in agreement with their ability to block sodium current. Thus a concentration-related increase in the threshold current required to elicit an action potential as observed along with a decrease in the amplitude and a shortening of the latency of action potential and a decrease in the firing capability of the membrane. Again the R-(-) isomers were more potent than the S-(+) ones and mexiletine was more effective than tocainide. These data corroborate the presence of a stereospecific site for these

  9. Behavioral Responses of Plum Curculio (Coleoptera: Curculionidae) to Different Enantiomer Concentrations and Blends of the Synthetic Aggregation Pheromone Grandisoic Acid.

    PubMed

    Hock, Virginia; Chouinard, Gérald; Lucas, Éric; Cormier, Daniel; Leskey, Tracy C; Wright, Starker E; Zhang, Aijun; Pichette, André

    2015-04-01

    The plum curculio, Conotrachelus nenuphar (Herbst) (Coleoptera: Curculionidae), is an important pest of fruit in North America. Males produce an aggregation pheromone (grandisoic acid) that attracts both sexes of the northern univoltine and the southern multivoltine strains. Grandisoic acid ((1R,2S)-1-methyl-2-(1-methylethenyl)-cyclobutaneacetic acid) is a chiral molecule containing one chiral center. A synthetic racemic mixture will contain two optical isomers that are mirror images of each other with equal amounts of (+)- and (-)-enantiomeric isomers. Male plum curculio only produce the (+) enantiomer. Some enantiomers can have antagonistic effects on the attraction of weevils to pheromones. An understanding of the effect of both enantiomers on the behaviour of plum curculio is needed to develop more efficient trap baits. Behavioural bioassays were conducted in a dual-choice still-air vertical olfactometer using a quantity of 1.5 ml of both (+) and (-) synthetic enantiomers and the racemic mixture of grandisoic acid with live female responders to determine which concentration and enantiomeric purity is the most attractive and if there is an antagonistic effect of the unnatural (-) enantiomer. Results indicated that plum curculio were attracted to low concentrations of the (+) enantiomer at 72% enantiomeric excess, but that strains were attracted to different concentrations of the (+) enantiomer (2×10(-7) mg/ml for univoltine, 2×10(-9) mg/ml for multivoltine).

  10. Behavioral Responses of Plum Curculio (Coleoptera: Curculionidae) to Different Enantiomer Concentrations and Blends of the Synthetic Aggregation Pheromone Grandisoic Acid.

    PubMed

    Hock, Virginia; Chouinard, Gérald; Lucas, Éric; Cormier, Daniel; Leskey, Tracy C; Wright, Starker E; Zhang, Aijun; Pichette, André

    2015-04-01

    The plum curculio, Conotrachelus nenuphar (Herbst) (Coleoptera: Curculionidae), is an important pest of fruit in North America. Males produce an aggregation pheromone (grandisoic acid) that attracts both sexes of the northern univoltine and the southern multivoltine strains. Grandisoic acid ((1R,2S)-1-methyl-2-(1-methylethenyl)-cyclobutaneacetic acid) is a chiral molecule containing one chiral center. A synthetic racemic mixture will contain two optical isomers that are mirror images of each other with equal amounts of (+)- and (-)-enantiomeric isomers. Male plum curculio only produce the (+) enantiomer. Some enantiomers can have antagonistic effects on the attraction of weevils to pheromones. An understanding of the effect of both enantiomers on the behaviour of plum curculio is needed to develop more efficient trap baits. Behavioural bioassays were conducted in a dual-choice still-air vertical olfactometer using a quantity of 1.5 ml of both (+) and (-) synthetic enantiomers and the racemic mixture of grandisoic acid with live female responders to determine which concentration and enantiomeric purity is the most attractive and if there is an antagonistic effect of the unnatural (-) enantiomer. Results indicated that plum curculio were attracted to low concentrations of the (+) enantiomer at 72% enantiomeric excess, but that strains were attracted to different concentrations of the (+) enantiomer (2×10(-7) mg/ml for univoltine, 2×10(-9) mg/ml for multivoltine). PMID:26470165

  11. Pharmacokinetics and pharmacodynamics of (+)-primaquine and (-)-primaquine enantiomers in rhesus macaques (Macaca mulatta).

    PubMed

    Saunders, David; Vanachayangkul, Pattaraporn; Imerbsin, Rawiwan; Khemawoot, Phisit; Siripokasupkul, Raveewan; Tekwani, Babu L; Sampath, Aruna; Nanayakkara, N P Dhammika; Ohrt, Colin; Lanteri, Charlotte; Gettyacamin, Montip; Teja-Isavadharm, Paktiya; Walker, Larry

    2014-12-01

    Primaquine (PQ) remains the sole available drug to prevent relapse of Plasmodium vivax malaria more than 60 years after licensure. While this drug was administered as a racemic mixture, prior studies suggested a pharmacodynamic advantage based on differential antirelapse activity and/or toxicities of its enantiomers. Oral primaquine enantiomers prepared using a novel, easily scalable method were given for 7 days to healthy rhesus macaques in a dose-rising fashion to evaluate their effects on the blood, liver, and kidneys. The enantiomers were then administered to Plasmodium cynomolgi-infected rhesus macaques at doses of 1.3 and 0.6 mg/kg of body weight/day in combination with chloroquine. The (-)-PQ enantiomer had higher clearance and apparent volume of distribution than did (+)-PQ and was more extensively converted to the carboxy metabolite. There is evidence for differential oxidative stress with a concentration-dependent rise in methemoglobin (MetHgb) with increasing doses of (+)-PQ greater than that seen for (-)-PQ. There was a marked, reversible hepatotoxicity in 2 of 3 animals dosed with (-)-PQ at 4.5 mg/kg. (-)-PQ in combination with chloroquine was successful in preventing P. cynomolgi disease relapse at doses of 0.6 and 1.3 mg/kg/day, while 1 of 2 animals receiving (+)-PQ at 0.6 mg/kg/day relapsed. While (-)-PQ was also associated with hepatotoxicity at higher doses as seen previously, this has not been identified as a clinical concern in humans during >60 years of use. Limited evidence for increased MetHgb generation with the (+) form in the rhesus macaque model suggests that it may be possible to improve the therapeutic window for hematologic toxicity in the clinic by separating primaquine into its enantiomers. PMID:25267666

  12. Interindividual differences in o,p'-DDD enantiomer kinetics examined in Göttingen minipigs.

    PubMed

    Cantillana, T; Lindström, V; Eriksson, L; Brandt, I; Bergman, A

    2009-06-01

    Five minipigs were given a single oral dose of a racemic mixture of o,p'-DDD (30 mg kg(-1)b.w., EF=0.49). Blood plasma and subcutaneous adipose tissue were collected for analysis, at different time-points over 180 d. At the end of the experiment also liver, kidney and brain tissue were collected. Low concentrations of o,p'-DDD still remained after 180 d in plasma (mean 0.5+/-0.3 ng g(-1)f.w.) and in adipose tissue (mean 40+/-40 ng g(-1)f.w.). The mean concentrations in liver and kidney were 500+/-300 pg g(-1)f.w. and 90+/-50 pg g(-1)f.w., respectively. The enantiomers of o,p'-DDD were isolated by HPLC and the absolute configuration of the enantiomers were determined by X-ray crystallography and polarimetry as R-(+)-o,p'-DDD and S-(-)-o,p'-DDD. The enantiomer fractions (EFs) of o,p'-DDD were determined in plasma, adipose tissue and kidney using GC/ECD equipped with a chiral column. The EFs of o,p'-DDD in the individual minipigs showed large variability, ranging from 0.2 to 0.6 after 24h in plasma and from 0.2 to 0.7 after 90 d in adipose tissue. Hence in two of the minipigs, the S-(-)-o,p'-DDD enantiomer was dominating while the other enantiomer, R-(+)-o,p'-DDD was dominating in three minipigs. We propose that a yet not identified factor related to polymorphism, regulating the metabolism and/or elimination of the enantiomeric o,p'-DDD, is responsible for the differences in enantiomeric retention of the compound in the minipigs.

  13. New insights into the site and mode of antinociceptive action of flurbiprofen enantiomers.

    PubMed

    Geisslinger, G; Schaible, H G

    1996-06-01

    The S-enantiomer of flurbiprofen has been shown to have both antiinflammatory and antinociceptive effects, whereas R-flurbiprofen is antinociceptive but not antiinflammatory. Importantly, only S-flurbiprofen inhibited prostaglandin biosynthesis in vitro at therapeutic concentrations. R-flurbiprofen did not undergo significant chiral inversion to S-flurbiprofen in rats and humans. A study was conducted to gain new insight into the possible sites and modes of action of flurbiprofen enantiomers. In a modified Randall Selitto assay, both enantiomers were antinociceptive in a dose-dependent manner after systemic administration. After local administration into the inflamed paw, only S-flurbiprofen produced significant dose-related antinociception. In a physiologic study, we recorded extracellularly from nociceptive spinal cord neurons that were rendered hyperexcitable. Intravenous administration of R- and S-flurbiprofen reduced responses of neurons to pressure applied to the inflamed knee and the noninflamed ankle and paw in a dose-dependent manner. When injected directly into the knee joint, only S-flurbiprofen but not R-flurbiprofen reduced responses to pressure. These results suggest a central site of antinociceptive action for R- and S-flurbiprofen and an additional peripheral site for S-flurbiprofen. The findings may be of clinical relevance, as it was demonstrated that both enantiomers also were antinociceptive in humans. Because R-flurbiprofen caused less toxicity in rats than the S-enantiomer or the racemic compound, a reduction in the quantitatively most important side effects in the gastrointestinal tract might be achieved with the use of R-flurbiprofen for pain therapy.

  14. Steady-state plasma concentration of donepezil enantiomers and its stereoselective metabolism and transport in vitro.

    PubMed

    Lili, Wan; Cheng, Guo; Zhiyong, Zhou; Qi, Yu; Yan, Li; Dan, Li; Xueli, Zheng; Yuan, Zhong

    2013-09-01

    The aim of the present study was to elucidate the differences in the plasma concentration of two enantiomers of donepezil in Chinese patients with Alzheimer's disease (AD) and investigate in vitro stereoselective metabolism and transport. Donepezil enantiomers were separated and determined by LC-MS/MS using D5-donepezil as an internal standard on a Sepax Chiralomix SB-5 column. In vitro stereoselective metabolism and transport of donepezil were investigated in human liver microsomes and MDCKII-MDR1 cell monolayer. Pre-dose (Css-min) plasma concentrations were determined in 52 patients. The mean plasma level of (R)-donepezil was 14.94 ng/ml and that of (S)-donepezil was 23.37 ng/ml. One patient's plasma concentration of (R)-donepezil was higher than (S)-donepezil and the ratio is 1.51. The mean plasma levels of (S)-donepezil were found to be higher than those of (R)-donepezil in 51 patients and the ratio of plasma (R)- to (S)-donepezil varies from 0.34 to 0.85. In the in vitro microsomal system, (R)-donepezil degraded faster than (S)-donepezil. V(max) of (R)-donepezil was significantly higher than (S)-donepezil. The P-gp inhibition experiment shown that the P(app) of the two enantiomers was higher than 200 and the efflux ratios were 1.11 and 0.99. The results of the P-gp inhibition identification experiment showed IC50 values of 35.5 and 20.4 μM, respectively, for the two enantiomers. The results indicate that donepezil exhibits stereoselective hepatic metabolism that may explain the differences in the steady-state plasma concentrations observed. Neither (R)- nor (S)-donepezil was a P-gp substance and the two enantiomers are highly permeable through the blood-brain barrier.

  15. Stereoselectivity of chiral drug transport: a focus on enantiomer-transporter interaction.

    PubMed

    Zhou, Quan; Yu, Lu-Shan; Zeng, Su

    2014-08-01

    Drug transporters and drug metabolism enzymes govern drug absorption, distribution, metabolism and elimination. Many literature works presenting important aspects related to stereochemistry of drug metabolism are available. However, there is very little literature on stereoselectivity of chiral drug transport and enantiomer-transporter interaction. In recent years, the experimental research within this field showed good momentum. Herein, an up-to-date review on this topic was presented. Breast Cancer Resistance Protein (BCRP), Multidrug Resistance Proteins (MRP), P-glycoprotein (P-gp), Organic Anion Transporters (OATs), Organic Anion Transporting Polypeptides (OATPs), Organic Cation Transporters (OCTs), Peptide Transport Proteins (PepTs), Human Proton-Coupled Folate Transporter (PCFT) and Multidrug and Toxic Extrusion Proteins (MATEs), have been reported to exhibit either positive or negative enantio-selective substrate recognition. The approaches utilized to study chirality in enantiomer-transporter interaction include inhibition experiments of specific transporters in cell models (e.g. Caco-2 cells), transport study using drug resistance cell lines or transgenic cell lines expressing transporters in wild type or variant, the use of transporter knockout mice, pharmacokinetics association of single nucleotide polymorphism in transporters, pharmacokinetic interaction study of racemate in the presence of specific transporter inhibitor or inducer, molecule cellular membrane affinity chromatography and pharmacophore modeling. Enantiomer-enantiomer interactions exist in chiral transport. The strength and/or enantiomeric preference of stereoselectivity may be species or tissue-specific, concentration-dependent and transporter family member-dependent. Modulation of specific drug transporter by pure enantiomers might exhibit opposite stereoselectivity. Further studies with integrated approaches will open up new horizons in stereochemistry of pharmacokinetics. PMID:24796860

  16. Functioning methionine sulfoxide reductases A and B are present in human epidermal melanocytes in the cytosol and in the nucleus

    SciTech Connect

    Schallreuter, Karin U.; Chavan, Bhaven; Gillbro, Johanna M.

    2006-03-31

    Oxidation of methionine residues by reactive oxygen (ROS) in protein structures leads to the formation of methionine sulfoxide which can consequently lead to a plethora of impaired functionality. The generation of methionine sulfoxide yields ultimately a diastereomeric mixture of the S and R sulfoxides. So far two distinct enzyme families have been identified. MSRA reduces methionine S-sulfoxide, while MSRB reduces the R-diastereomer. It has been shown that these enzymes are involved in regulation of protein function and in elimination of ROS via reversible methionine formation besides protein repair. Importantly, both enzymes require coupling to the NADPH/thioredoxin reductase/thioredoxin electron donor system. In this report, we show for First time the expression and function of both sulfoxide reductases together with thioredoxin reductase in the cytosol as well as in the nucleus of epidermal melanocytes which are especially sensitive to ROS. Since this cell resides in the basal layer of the epidermis and its numbers and functions are reduced upon ageing and for instance also in depigmentation processes, we believe that this discovery adds an intricate repair mechanism to melanocyte homeostasis and survival.

  17. Protection against adriamycin-induced skin necrosis in the rat by dimethyl sulfoxide and alpha-tocopherol.

    PubMed

    Svingen, B A; Powis, G; Appel, P L; Scott, M

    1981-09-01

    Extravasation of Adriamycin during i.v. infusion can cause serious local complications. We have used a rat skin model to study the protection afforded by dimethyl sulfoxide and alpha-tocopherol (vitamin E) against Adriamycin-induced skin necrosis. Topical daily application of 1 ml dimethyl sulfoxide for 2 days produced a small decrease in ulcer diameter of up to 11% at 2 weeks. Topical daily applications of 1 ml 10% alpha-tocopherol succinate in dimethyl sulfoxide for 2 days produced a marked decrease in ulcer diameter at 2 weeks of up to 68%. Daily topical application of 1 ml 10% alpha-tocopherol succinate in dimethyl sulfoxide for 7 days offered no greater protection than 2-day application. alpha-Tocopherol acetate appeared to have activity slightly less than that of alpha-tocopherol succinate in reducing ulcer size, and both compounds were considerably more active than was alpha-tocopherol alcohol. Administration of alpha-tocopherol succinate or alpha-tocopherol acetate i.p. had no significant effect upon ulcer diameter. Topically applied dimethyl sulfoxide and alpha-tocopherol may provide an effective way of treating accidentally extravasated Adriamycin in cancer patients.

  18. Activities of fenbendazole in comparison with albendazole against Echinococcus multilocularis metacestodes in vitro and in a murine infection model.

    PubMed

    Küster, Tatiana; Stadelmann, Britta; Aeschbacher, Denise; Hemphill, Andrew

    2014-04-01

    The current chemotherapeutic treatment of alveolar echinococcosis (AE) in humans is based on albendazole and/or mebendazole. However, the costs of treatment, life-long consumption of drugs, parasitostatic rather than parasiticidal activity of chemotherapy, and high recurrence rates after treatment interruption warrant more efficient treatment options. Experimental treatment of mice infected with Echinococcus multilocularis metacestodes with fenbendazole revealed similar efficacy to albendazole. Inspection of parasite tissue from infected and benzimidazole-treated mice by transmission electron microscopy (TEM) demonstrated drug-induced alterations within the germinal layer of the parasites, and most notably an almost complete absence of microtriches. On the other hand, upon in vitro exposure of metacestodes to benzimidazoles, no phosphoglucose isomerase activity could be detected in medium supernatants during treatment with any of these drugs, indicating that in vitro treatment did not severely affect the viability of metacestode tissue. Corresponding TEM analysis also revealed a dramatic shortening/retraction of microtriches as a hallmark of benzimidazole action, and as a consequence separation of the acellular laminated layer from the cellular germinal layer. Since TEM did not reveal any microtubule-based structures within Echinococcus microtriches, this effect cannot be explained by the previously described mechanism of action of benzimidazoles targeting β-tubulin, thus benzimidazoles must interact with additional targets that have not been yet identified. In addition, these results indicate the potential usefulness of fenbendazole for the chemotherapy of AE.

  19. A Methionine Residue Promotes Hyperoxidation of the Catalytic Cysteine of Mouse Methionine Sulfoxide Reductase A.

    PubMed

    Kim, Geumsoo; Levine, Rodney L

    2016-06-28

    Methionine sulfoxide reductase A (msrA) reduces methionine sulfoxide in proteins back to methionine. Its catalytic cysteine (Cys72-SH) has a low pKa that facilitates oxidation by methionine sulfoxide to cysteine sulfenic acid. If the catalytic cycle proceeds efficiently, the sulfenic acid is reduced back to cysteine at the expense of thioredoxin. However, the sulfenic acid is vulnerable to "irreversible" oxidation to cysteine sulfinic acid that inactivates msrA (hyperoxidation). We observed that human msrA is resistant to hyperoxidation while mouse msrA is readily hyperoxidized by micromolar concentrations of hydrogen peroxide. We investigated the basis of this difference in susceptibility to hyperoxidation and established that it is controlled by the presence or absence of a Met residue in the carboxyl-terminal domain of the enzyme, Met229. This residue is Val in human msrA, and when it was mutated to Met, human msrA became sensitive to hyperoxidation. Conversely, mouse msrA was rendered insensitive to hyperoxidation when Met229 was mutated to Val or one of five other residues. Positioning of the methionine at residue 229 is not critical, as hyperoxidation occurred as long as the methionine was located within the group of 14 carboxyl-terminal residues. The carboxyl domain of msrA is known to be flexible and to have access to the active site, and Met residues are known to form stable, noncovalent bonds with aromatic residues through interaction of the sulfur atom with the aromatic ring. We propose that Met229 forms such a bond with Trp74 at the active site, preventing formation of a protective sulfenylamide with Cys72 sulfenic acid. As a consequence, the sulfenic acid is available for facile, irreversible oxidation to cysteine sulfinic acid. PMID:27259041

  20. Formation of methionine sulfoxide during glycoxidation and lipoxidation of ribonuclease A.

    PubMed

    Brock, Jonathan W C; Ames, Jennifer M; Thorpe, Suzanne R; Baynes, John W

    2007-01-15

    Chemical modification of proteins by reactive oxygen species affects protein structure, function and turnover during aging and chronic disease. Some of this damage is direct, for example by oxidation of amino acids in protein by peroxide or other reactive oxygen species, but autoxidation of ambient carbohydrates and lipids amplifies both the oxidative and chemical damage to protein and leads to formation of advanced glycoxidation and lipoxidation end-products (AGE/ALEs). In previous work, we have observed the oxidation of methionine during glycoxidation and lipoxidation reactions, and in the present work we set out to determine if methionine sulfoxide (MetSO) in protein was a more sensitive indicator of glycoxidative and lipoxidative damage than AGE/ALEs. We also investigated the sites of methionine oxidation in a model protein, ribonuclease A (RNase), in order to determine whether analysis of the site specificity of methionine oxidation in proteins could be used to indicate the source of the oxidative damage, i.e. carbohydrate or lipid. We describe here the development of an LC/MS/MS for quantification of methionine oxidation at specific sites in RNase during glycoxidation or lipoxidation by glucose or arachidonate, respectively. Glycoxidized and lipoxidized RNase were analyzed by tryptic digestion, followed by reversed phase HPLC and mass spectrometric analysis to quantify methionine and methionine sulfoxide containing peptides. We observed that: (1) compared to AGE/ALEs, methionine sulfoxide was a more sensitive biomarker of glycoxidative or lipoxidative damage to proteins; (2) regardless of oxidizable substrate, the relative rate of oxidation of methionine residues in RNase was Met29>Met30>Met13, with Met79 being resistant to oxidation; and (3) arachidonate produced a significantly greater yield of MetSO, compared to glucose. The methods developed here should be useful for assessing a protein's overall exposure to oxidative stress from a variety of sources in

  1. Three-body dissociations: The photodissociation of dimethyl sulfoxide at 193 nm

    SciTech Connect

    Blank, D.A.; North, S.W.; Stranges, D.

    1997-04-01

    When a molecule with two equivalent chemical bonds is excited above the threshold for dissociation of both bonds, how the rupture of the two bonds is temporally coupled becomes a salient question. Following absorption at 193 nm dimethyl sulfoxide (CH{sub 3}SOCH{sub 3}) contains enough energy to rupture both C-S bonds. This can happen in a stepwise (reaction 1) or concerted (reaction 2) fashion where the authors use rotation of the SOCH{sub 3} intermediate prior to dissociation to define a stepwise dissociation: (1) CH{sub 3}SOCH{sub 3} {r_arrow} 2CH{sub 3} + SO; (2a) CH{sub 3}SOCH{sub 3} {r_arrow} CH{sub 3} + SOCH{sub 3}; and (2b) SOCH{sub 3} {r_arrow} SO + CH{sub 3}. Recently, the dissociation of dimethyl sulfoxide following absorption at 193 nm was suggested to involve simultaneous cleavage of both C-S bonds on an excited electronic surface. This conclusion was inferred from laser induced fluorescence (LIF) and resonant multiphoton ionization (2+1 REMPI) measurements of the internal energy content in the CH{sub 3} and SO photoproducts and a near unity quantum yield measured for SO. Since this type of concerted three body dissociation is very interesting and a rather rare event in photodissociation dynamics, the authors chose to investigate this system using the technique of photofragment translational spectroscopy at beamline 9.0.2.1. The soft photoionization provided by the VUV undulator radiation allowed the authors to probe the SOCH{sub 3} intermediate which had not been previously observed and provided good evidence that the dissociation of dimethyl sulfoxide primarily proceeds via a two step dissociation, reaction 2.

  2. Crystal structure of hexa-kis-(dimethyl sulfoxide-κO)manganese(II) diiodide.

    PubMed

    Glatz, Mathias; Schroffenegger, Martina; Weil, Matthias; Kirchner, Karl

    2016-07-01

    The asymmetric unit of the title salt, [Mn(C2H6OS)6]I2, consists of one Mn(II) ion, six O-bound dimethyl sulfoxide (DMSO) ligands and two I(-) counter-anions. The isolated complex cations have an octa-hedral configuration and are grouped in hexa-gonally arranged rows extending parallel to [100]. The two I(-) anions are located between the rows and are linked to the cations through two weak C-H⋯I inter-actions. PMID:27555928

  3. Isolation of dimethyl sulfone-degrading microorganisms and application to odorless degradation of dimethyl sulfoxide.

    PubMed

    Kino, Kuniki; Murakami-Nitta, Takako; Oishi, Masashi; Ishiguro, Seiji; Kirimura, Kohtaro

    2004-01-01

    With the objective of developing an odorless biodegradation process for dimethyl sulfoxide (DMSO), Hyphomicrobium sp. WU-OM3 was isolated. During the cultivation of strain WU-OM3 cells with 20 mM dimethyl sulfone (DMSO2) as the sole carbon source, DMSO2 was completely consumed within 48 h and sulfate ion accumulated in the culture broth. Methanesulfonate was also detected as an intermediate of DMSO2 degradation. By combining the DMSO-oxidizing microorganism and strain WU-OM3 cells, 0.64 mM (50 mg/l) DMSO was degraded to sulfate ion with 80% molar conversion ratio. PMID:16233595

  4. Effect of dimethyl sulfoxide addition on ultrasonic degradation of methylene blue

    NASA Astrophysics Data System (ADS)

    Shimakage, Kaho; Kobayashi, Daisuke; Naya, Masakazu; Matsumoto, Hideyuki; Shimada, Yuichiro; Otake, Katsuto; Shono, Atsushi

    2016-07-01

    The ultrasonic degradation of methylene blue was carried out in the absence and presence of dimethyl sulfoxide (DMSO) as a radical scavenger for various frequencies, and the effects of DMSO addition on the degradation rate constant estimated by assuming first-order kinetics were investigated. The degradation reaction rate decreased with DMSO addition, and hydroxyl radicals were observed to play important roles in the degradation of methylene blue. However, the degradation reaction did not stop with DMSO addition, and the degradation rate constant in the presence of DMSO was not affected by ultrasonic frequency.

  5. Crystal structure of hexa­kis­(dimethyl sulfoxide-κO)manganese(II) diiodide

    PubMed Central

    Glatz, Mathias; Schroffenegger, Martina; Weil, Matthias; Kirchner, Karl

    2016-01-01

    The asymmetric unit of the title salt, [Mn(C2H6OS)6]I2, consists of one MnII ion, six O-bound dimethyl sulfoxide (DMSO) ligands and two I− counter-anions. The isolated complex cations have an octa­hedral configuration and are grouped in hexa­gonally arranged rows extending parallel to [100]. The two I− anions are located between the rows and are linked to the cations through two weak C—H⋯I inter­actions. PMID:27555928

  6. Comparison of Dimethyl Sulfoxide and Water as Solvents for Echinocandin Susceptibility Testing by the EUCAST Methodology

    PubMed Central

    Alastruey-Izquierdo, Ana; Gómez-López, Alicia; Arendrup, Maiken C.; Lass-Florl, Cornelia; Hope, William W.; Perlin, David S.; Rodriguez-Tudela, Juan L.

    2012-01-01

    Ninety-six strains of Candida, including 29 resistant and 67 susceptible isolates with mutations in the FKS1 and FKS2 genes were tested by the European Committee on Antibiotic Susceptibility Testing EDef 7.1 and 7.2 methodologies to determine the impact on the MIC when water was replaced with dimethyl sulfoxide (DMSO) as the solvent for caspofungin and micafungin. The MICs were significantly lower and the MIC ranges were narrower when DMSO was used as the solvent. The use of DMSO may help to better discriminate between susceptible and resistant populations. PMID:22535988

  7. Size-exclusion chromatography of technical lignins in dimethyl sulfoxide/water and dimethylacetamide.

    PubMed

    Ringena, Okko; Lebioda, Sascha; Lehnen, Ralph; Saake, Bodo

    2006-01-13

    Well defined spent sulfite liquor samples and lignosulfonate fractions obtained by ultrafiltration were analyzed using size-exclusion chromatography. Two different eluent systems (dimethyl sulfoxide/water/lithium bromide; dimethylacetamide/lithium chloride) were compared regarding their suitability for lignin analysis. The differences of the elution profiles and calculated molar masses were discussed using conventional and universal calibration. For further validation four technical lignins from a Round Robin test were included into the study. The results indicated that both analytical systems under investigation were well suited for the analysis of technical lignins. PMID:16288767

  8. In vivo activity of albendazole in combination with thymol against Echinococcus multilocularis.

    PubMed

    Albani, Clara María; Pensel, Patricia Eugenia; Elissondo, Natalia; Gambino, Guillermo; Elissondo, María Celina

    2015-09-15

    Human alveolar echinococcosis (AE) is caused by the fox tapeworm Echinococcus multilocularis and is usually lethal if left untreated. The current strategy for treating human AE is surgical resection of the parasite mass complemented by chemotherapy with benzimidazole compounds. However, reliable chemotherapeutic alternatives have not yet been developed stimulating the research of new treatment strategies such as the use of medicinal plants. The aim of the current study was to investigate the efficacy of the combination albendazole (ABZ)+thymol on mice infected with E. multilocularis metacestodes. For this purpose, mice infected with parasite material were treated daily for 20 days with ABZ (5 mg/kg), thymol (40 mg/kg) or ABZ (5 mg/kg)+thymol (40 mg/kg) or left untreated as controls. After mice were euthanized, cysts were removed from the peritoneal cavity and the treatment efficacy was evaluated by the mean cysts weight, viability of protoscoleces and ultrastructural changes of cysts and protoscoleces. The application of thymol or the combination of ABZ+thymol resulted in a significant reduction of the cysts weight compared to untreated mice. We also found that although ABZ and thymol had a scolicidal effect, the combination of the two compounds had a considerably stronger effect showing a reduction in the protoscoleces viability of 62%. These results were also corroborated by optical microscopy, SEM and TEM. Protoscoleces recovered from ABZ or thymol treated mice showed alterations as contraction of the soma region, rostellar disorganization and presence of blebs in the tegument. However both drugs when combined lead to a total loss of the typical morphology of protoscoleces. All cysts removed from control mice appeared intact and no change in ultrastructure was detected. In contrast, cysts developed in mice treated with ABZ revealed changes in the germinal layer as reduction in cell number, while the treatment with thymol or the ABZ+thymol combination

  9. A QSPR study on the solvent-induced frequency shifts of acetone and dimethyl sulfoxide in organic solvents

    NASA Astrophysics Data System (ADS)

    Ou, Yu Heng; Chang, Chia Ming; Chen, Ying Shao

    2016-06-01

    In this study, solvent-induced frequency shifts (SIFS) in the infrared spectrum of acetone and dimethyl sulfoxide in organic solvents were investigated by using four types of quantum-chemical reactivity descriptors. The results showed that the SIFS of acetone is mainly affected by the electron-acceptance chemical potential and the maximum nucleophilic condensed local softness of organic solvents, which represent the electron flow and the polarization between acetone and solvent molecules. On the other hand, the SIFS of dimethyl sulfoxide changes with the maximum positive charge of hydrogen atom and the inverse of apolar surface area of solvent molecules, showing that the electrostatic and hydrophilic interactions are main mechanisms between dimethyl sulfoxide and solvent molecules. The introduction of the four-element theory model-based quantitative structure-property relationship approach improved the assessing quality and provided a basis for interpreting the solute-solvent interactions.

  10. Effect of nonionic surfactants on percutaneous absorption of salicylic acid and sodium salicylate in the presence of dimethyl sulfoxide.

    PubMed

    Shen, W W; Danti, A G; Bruscato, F N

    1976-12-01

    Fifteen nonionic surfactants, 10% (w/w), were each incorporated into white petrolatum USP ointment base containing 10% (w/w) salicylic acid or 11.6% (w/w) sodium salicylate with 10% (w/w) dimethyl sulfoxide. Percutaneous absorption was determined from blood salicylate levels in New Zealand white rabbits at regular intervals for 8 hr following application of the ointment. Percutaneous absorption of salicylic acid was increased significantly when sorbitan monopalmitate, sorbitan trioleate, poloxamer 231, poloxamer 182, polyoxyethylene 4 lauryl ether, polyoxyethylene 2 oleyl ether, or polyoxyl 8 stearate was added to the ointment containing dimethyl sulfoxide, salicylic acid, and white petrolatum. Percutaneous absorption of sodium salicylate was increased significantly when sorbitan monolaurate, sorbitan monopalmitate, or poloxamer 182 was added to the ointment containing dimethyl sulfoxide, sodium salicylate, and white petrolatum.

  11. A QSPR study on the solvent-induced frequency shifts of acetone and dimethyl sulfoxide in organic solvents.

    PubMed

    Ou, Yu Heng; Chang, Chia Ming; Chen, Ying Shao

    2016-06-01

    In this study, solvent-induced frequency shifts (SIFS) in the infrared spectrum of acetone and dimethyl sulfoxide in organic solvents were investigated by using four types of quantum-chemical reactivity descriptors. The results showed that the SIFS of acetone is mainly affected by the electron-acceptance chemical potential and the maximum nucleophilic condensed local softness of organic solvents, which represent the electron flow and the polarization between acetone and solvent molecules. On the other hand, the SIFS of dimethyl sulfoxide changes with the maximum positive charge of hydrogen atom and the inverse of apolar surface area of solvent molecules, showing that the electrostatic and hydrophilic interactions are main mechanisms between dimethyl sulfoxide and solvent molecules. The introduction of the four-element theory model-based quantitative structure-property relationship approach improved the assessing quality and provided a basis for interpreting the solute-solvent interactions. PMID:26994584

  12. Stereoselective Degradation of alpha-Cypermethrin and Its Enantiomers in Rat Liver Microsomes.

    PubMed

    Yan, Jin; Zhang, Ping; Wang, Xinru; Xu, Meiqi; Wang, Yao; Zhou, Zhiqiang; Zhu, Wentao

    2016-01-01

    Alpha-cypermethrin (α-CP), [(RS)-a-cyano-3-phenoxy benzyl (1RS)-cis-3-(2, 2-dichlorovinyl)-2, 2-dimethylcyclopropanecarboxylate], comprises a diastereoisomer pair of cypermethrin, which are (+)-(1R-cis-αS)-CP (insecticidal) and (-)-(1S-cis-αR)-CP (inactive). In this experiment, the stereoselective degradation of α-CP was investigated in rat liver microsomes by high-performance liquid chromatography (HPLC) with a cellulose-tris- (3, 5-dimethylphenylcarbamate)-based chiral stationary phase. The results revealed that the degradation of (-)-(1S-cis-αR)-CP was much faster than (+)-(1R-cis-αS)-CP both in enantiomer monomers and rac-α-CP. As for the enzyme kinetic parameters, there were some variances between rac-α-CP and the enantiomer monomers. In rac-α-CP, the Vmax and CLint of (+)-(1R-cis-αS)-CP (5105.22 ± 326.26 nM/min/mg protein and 189.64 mL/min/mg protein) were about one-half of those of (-)-(1S-cis-αR)-CP (9308.57 ± 772.24 nM/min/mg protein and 352.19 mL/min/mg protein), while the Km of the two α-CP enantiomers were similar. However, in the enantiomer monomers of α-CP, the Vmax and Km of (+)-(1R-cis-αS) -CP were 2-fold and 5-fold of (-)-(1S-cis-αR)-CP, respectively, which showed a significant difference with rac-α-CP. The CLint of (+)-(1R-cis-αS)-CP (140.97 mL/min/mg protein) was still about one-half of (-)-(1S-cis-αR)-CP (325.72 mL/min/mg protein) in enantiomer monomers. The interaction of enantiomers of α-CP in rat liver microsomes was researched and the results showed that there were different interactions between the IC50 of (-)- to (+)-(1R-cis-αS)-CP and (+)- to (-)-(1S-cis-αR)-CP(IC50(-)/(+) / IC50(+)/(-)  = 0.61).

  13. Randomized, controlled, assessor-blind clinical trial to assess the efficacy of single- versus repeated-dose albendazole to treat ascaris lumbricoides, trichuris trichiura, and hookworm infection.

    PubMed

    Adegnika, Ayola A; Zinsou, Jeannot F; Issifou, Saadou; Ateba-Ngoa, Ulysse; Kassa, Roland F; Feugap, Eliane N; Honkpehedji, Yabo J; Dejon Agobe, Jean-Claude; Kenguele, Hilaire M; Massinga-Loembe, Marguerite; Agnandji, Selidji T; Mordmüller, Benjamin; Ramharter, Michael; Yazdanbakhsh, Maria; Kremsner, Peter G; Lell, Bertrand

    2014-05-01

    In many regions where soil-transmitted helminth infections are endemic, single-dose albendazole is used in mass drug administration programs to control infections. There are little data on the efficacy of the standard single-dose administration compared to that of alternative regimens. We conducted a randomized, controlled, assessor-blinded clinical trial to determine the efficacies of standard and extended albendazole treatment against soil-transmitted helminth infection in Gabon. A total of 175 children were included. Adequate cure rates and egg reduction rates above 85% were found with a single dose of albendazole for Ascaris infection, 85% (95% confidence interval [CI], 73, 96) and 93.8% (CI, 87.6, 100), respectively, while two doses were necessary for hookworm infestation (92% [CI, 78, 100] and 92% [CI, 78, 100], respectively). However, while a 3-day regimen was not sufficient to cure Trichuris (cure rate, 83% [CI, 73, 93]), this regimen reduced the number of eggs up to 90.6% (CI, 83.1, 100). The rate ratios of two- and three-dose regimens compared to a single-dose treatment were 1.7 (CI, 1.1, 2.5) and 2.1 (CI, 1.5, 2.9) for Trichuris and 1.7 (CI, 1.0, 2.9) and 1.7 (CI, 1.0, 2.9) for hookworm. Albendazole was safe and well tolerated in all regimens. A single-dose albendazole treatment considerably reduces Ascaris infection but has only a moderate effect on hookworm and Trichuris infections. The single-dose option may still be the preferred regimen because it balances efficacy, safety, and compliance during mass drug administration, keeping in mind that asymptomatic low-level helminth carriage may also have beneficial effects. (This study has been registered at ClinicalTrials.gov under registration number NCT01192802.).

  14. A general and expeditious one-pot synthesis of sulfoxides in high optical purity from norephedrine-derived sulfamidites.

    PubMed

    García Ruano, José L; Alemparte, Carlos; Aranda, M Teresa; Zarzuelo, María M

    2003-01-01

    A general and simple procedure for preparing any kind of enantiomerically enriched sulfoxide starting from norephedrine-derived N-benzyloxycarbonylsulfamidite 3a is reported. After one-pot reaction of 3a with RMgX, HBF(4), and R'MgX, a variety of sulfoxides 6 are obtained in ee usually higher than 93% and isolated yields ranging between 50 and 78%. The obtained configuration is tunable by simply electing the order of the addition of the reagents. [reaction--see text

  15. A DFT-D study on the electronic and photophysical properties of ruthenium (II) complex with a chelating sulfoxide group

    NASA Astrophysics Data System (ADS)

    Li, Huifang; Zhang, Lisheng; Lin, Hui; Fan, Xiaolin

    2014-06-01

    Electronic and photophysical properties of [Ru(bpy)2(OSO)]+ (bpy = 2,2‧-bipyridine; OSO = methylsulfinylbenzoate) were examined theoretically to better understand the differences between S- and O-linked ruthenium sulfoxide complexes. It is found that the strength of Ru-O1 linkage is significantly larger than that of Ru-S linkage, which makes the charge transfer amount from surrounding ligands to central Ru decreased. The energy gap is closed due to the highest occupied molecular orbital energy increases to a larger extent than the lowest unoccupied molecular orbital energy. Thereby, red shifted absorption and emission maxima in such photochromic ruthenium sulfoxide complexes can be explained.

  16. Methionine sulfoxide reductase A deficiency exacerbates progression of kidney fibrosis induced by unilateral ureteral obstruction.

    PubMed

    Kim, Jee In; Noh, Mi Ra; Kim, Ki Young; Jang, Hee-Seong; Kim, Hwa-Young; Park, Kwon Moo

    2015-12-01

    Methionine sulfoxide reductase A (MsrA), which stereospecifically catalyzes the reduction of methionine-S-sulfoxide, is an important reactive oxygen species (ROS) scavenger. Tissue fibrosis is a maladaptive repair process following injury, associated with oxidative stress. In this study, we investigated the role of MsrA in unilateral ureteral obstruction (UUO)-induced kidney fibrosis and its underlying mechanisms by using MsrA gene-deleted mice (MsrA(-/-)). MsrA deletion increased collagen deposition in the interstitium and the expression of collagen III and α-smooth muscle actin in the UUO kidneys, indicating that MsrA deficiency exacerbated the progression of UUO-induced kidney fibrosis. UUO reduced the kidney expression of MsrA, MsrB1, and MsrB2, thereby decreasing MsrA and MsrB activity. UUO increased hydrogen peroxide and lipid peroxidation levels and the ratio of oxidized glutathione (GSSG) to total glutathione (GSH) in the kidneys. The UUO-induced elevations in the levels of these oxidative stress markers and leukocyte markers were much higher in the MsrA(-/-) than in the MsrA(+/+) kidneys, the latter suggesting that the exacerbated kidney fibrosis in MsrA(-/-) mice was associated with enhanced inflammatory responses. Collectively, our data suggest that MsrA plays a protective role in the progression of UUO-induced kidney fibrosis via suppression of fibrotic responses caused by oxidative stress and inflammation.

  17. Protective roles of methionine-R-sulfoxide reductase against stresses in Schizosaccharomyces pombe.

    PubMed

    Jo, Hannah; Cho, Young-Wook; Ji, Sun-Young; Kang, Ga-Young; Lim, Chang-Jin

    2014-01-01

    The Schizosaccharomyces pombe msrB(+) gene encoding methionine-R-sulfoxide reductase (MsrB) was cloned into the shuttle vector pRS316 to generate the recombinant plasmid pFMetSO. The msrB(+) mRNA level was significantly increased in the S. pombe cells harboring pFMetSO, indicating that the cloned msrB(+) gene is functioning. In the presence of 0.1 mM L-methionine-(R,S)-sulfoxide, the S. pombe cells harboring pFMetSO could grow normally but the growth of the vector control cells was almost arrested. The S. pombe cells harboring pFMetSO exhibited the enhanced growth on the minimal medium plates with stress-inducing agents, such as hydrogen peroxide, superoxide radical-generating menadione (MD), nitric oxide (NO)-generating sodium nitroprusside (SNP), and cadmium (Cd), when compared with the vector control cells. They also gave rise to the enhanced growth at the high incubation temperature of 37 °C than the vector control cells. The S. pombe cells harboring pFMetSO contained lower reactive oxygen species (ROS) and higher total glutathione (GSH) levels than the vector control cells. In brief, the S. pombe MsrB plays a protective role against oxidative, nitrosative, and thermal stresses, and is involved in diminishing intracellular ROS level.

  18. Evidence for participation of the methionine sulfoxide reductase repair system in plant seed longevity

    PubMed Central

    Châtelain, Emilie; Satour, Pascale; Laugier, Edith; Ly Vu, Benoit; Payet, Nicole; Rey, Pascal; Montrichard, Françoise

    2013-01-01

    Seeds are in a natural oxidative context leading to protein oxidation. Although inevitable for proper progression from maturation to germination, protein oxidation at high levels is detrimental and associated with seed aging. Oxidation of methionine to methionine sulfoxide is a common form of damage observed during aging in all organisms. This damage is reversible through the action of methionine sulfoxide reductases (MSRs), which play key roles in lifespan control in yeast and animal cells. To investigate the relationship between MSR capacity and longevity in plant seeds, we first used two Medicago truncatula genotypes with contrasting seed quality. After characterizing the MSR family in this species, we analyzed gene expression and enzymatic activity in immature and mature seeds exhibiting distinct quality levels. We found a very strong correlation between the initial MSR capacities in different lots of mature seeds of the two genotypes and the time to a drop in viability to 50% after controlled deterioration. We then analyzed seed longevity in Arabidopsis thaliana lines, in which MSR gene expression has been genetically altered, and observed a positive correlation between MSR capacity and longevity in these seeds as well. Based on our data, we propose that the MSR repair system plays a decisive role in the establishment and preservation of longevity in plant seeds. PMID:23401556

  19. Structural Insights into Interaction between Mammalian Methionine Sulfoxide Reductase B1 and Thioredoxin

    PubMed Central

    Dobrovolska, Olena; Rychkov, Georgy; Shumilina, Elena; Nerinovski, Kirill; Schmidt, Alexander; Shabalin, Konstantin; Yakimov, Alexander; Dikiy, Alexander

    2012-01-01

    Maintenance of the cellular redox balance has vital importance for correcting organism functioning. Methionine sulfoxide reductases (Msrs) are among the key members of the cellular antioxidant defence system. To work properly, methionine sulfoxide reductases need to be reduced by their biological partner, thioredoxin (Trx). This process, according to the available kinetic data, represents the slowest step in the Msrs catalytic cycle. In the present paper, we investigated structural aspects of the intermolecular complex formation between mammalian MsrB1 and Trx. NMR spectroscopy and biocomputing were the two mostly used through the research approaches. The formation of NMR detectable MsrB1/Trx complex was monitored and studied in attempt to understand MsrB1 reduction mechanism. Using NMR data, molecular mechanics, protein docking, and molecular dynamics simulations, it was found that intermediate MsrB1/Trx complex is stabilized by interprotein β-layer. The complex formation accompanied by distortion of disulfide bond within MsrB1 facilitates the reduction of oxidized MsrB1 as it is evidenced by the obtained data. PMID:22505815

  20. Dimethyl sulfoxide can initiate cell divisions of arrested callus protoplasts by promoting cortical microtubule assembly

    PubMed Central

    Hahne, Günther; Hoffmann, Franz

    1984-01-01

    A serious problem in the technology of plant cell culture is that isolated protoplasts from many species are reluctant to divide. We have succeeded in inducing consecutive divisions in a “naturally” arrested system—i.e., protoplasts from a hibiscus cell line, which do not divide under standard conditions—and in an artificially arrested system—i.e., colchicine-inhibited callus protoplasts of Nicotiana glutinosa, which do readily divide in the absence of colchicine. In both cases, the reinstallation of a net of cortical microtubules, which had been affected either by colchicine or by the protoplast isolation procedure, resulted in continuous divisions of the formerly arrested protoplasts. Several compounds known to support microtubule assembly in vitro were tested for their ability to promote microtubule assembly in vivo. Best results were obtained by addition of dimethyl sulfoxide to the culture medium. Unlimited amounts of callus could be produced with the dimethyl sulfoxide method from protoplasts which never developed a single callus in control experiments. Images PMID:16593508

  1. Apratoxin H and apratoxin A sulfoxide from the Red Sea cyanobacterium Moorea producens.

    PubMed

    Thornburg, Christopher C; Cowley, Elise S; Sikorska, Justyna; Shaala, Lamiaa A; Ishmael, Jane E; Youssef, Diaa T A; McPhail, Kerry L

    2013-09-27

    Cultivation of the marine cyanobacterium Moorea producens, collected from the Nabq Mangroves in the Gulf of Aqaba (Red Sea), led to the isolation of new apratoxin analogues apratoxin H (1) and apratoxin A sulfoxide (2), together with the known apratoxins A-C, lyngbyabellin B, and hectochlorin. The absolute configuration of these new potent cytotoxins was determined by chemical degradation, MS, NMR, and CD spectroscopy. Apratoxin H (1) contains pipecolic acid in place of the proline residue present in apratoxin A, expanding the known suite of naturally occurring analogues that display amino acid substitutions within the final module of the apratoxin biosynthetic pathway. The oxidation site of apratoxin A sulfoxide (2) was deduced from MS fragmentation patterns and IR data, and 2 could not be generated experimentally by oxidation of apratoxin A. The cytotoxicity of 1 and 2 to human NCI-H460 lung cancer cells (IC₅₀ = 3.4 and 89.9 nM, respectively) provides further insight into the structure-activity relationships in the apratoxin series. Phylogenetic analysis of the apratoxin-producing cyanobacterial strains belonging to the genus Moorea, coupled with the recently annotated apratoxin biosynthetic pathway, supports the notion that apratoxin production and structural diversity may be specific to their geographical niche.

  2. The Protein Oxidation Repair Enzyme Methionine Sulfoxide Reductase A Modulates Aβ Aggregation and Toxicity In Vivo

    PubMed Central

    Minniti, Alicia N.; Arrazola, Macarena S.; Bravo-Zehnder, Marcela; Ramos, Francisca; Inestrosa, Nibaldo C.

    2015-01-01

    Abstract Aims: To examine the role of the enzyme methionine sulfoxide reductase A-1 (MSRA-1) in amyloid-β peptide (Aβ)-peptide aggregation and toxicity in vivo, using a Caenorhabditis elegans model of the human amyloidogenic disease inclusion body myositis. Results: MSRA-1 specifically reduces oxidized methionines in proteins. Therefore, a deletion of the msra-1 gene was introduced into transgenic C. elegans worms that express the Aβ-peptide in muscle cells to prevent the reduction of oxidized methionines in proteins. In a constitutive transgenic Aβ strain that lacks MSRA-1, the number of amyloid aggregates decreases while the number of oligomeric Aβ species increases. These results correlate with enhanced synaptic dysfunction and mislocalization of the nicotinic acetylcholine receptor ACR-16 at the neuromuscular junction (NMJ). Innovation: This approach aims at modulating the oxidation of Aβ in vivo indirectly by dismantling the methionine sulfoxide repair system. The evidence presented here shows that the absence of MSRA-1 influences Aβ aggregation and aggravates locomotor behavior and NMJ dysfunction. The results suggest that therapies which boost the activity of the Msr system could have a beneficial effect in managing amyloidogenic pathologies. Conclusion: The absence of MSRA-1 modulates Aβ-peptide aggregation and increments its deleterious effects in vivo. Antioxid. Redox Signal. 22, 48–62. PMID:24988428

  3. Dimethyl sulfoxide can initiate cell divisions of arrested callus protoplasts by promoting cortical microtuble assembly

    SciTech Connect

    Hahne, G.; Hoffmann, F.

    1984-09-01

    A serious problem in the technology of plant cell culture is that isolated protoplasts from many species are reluctant to divide. We have succeeded in inducing consecutive divisions in a naturally arrested system i.e., protoplasts from a hibiscus cell line, which do not divide under standard conditions and in an artificially arrested system i.e., colchicine-inhibited callus protoplasts of Nicotiana glutinosa, which do readily divide in the absence of colchicine. In both cases, the reinstallation of a net of cortical microtubules, which had been affected either by colchicine or by the protoplast isolation procedure, resulted in continuous divisions of the formerly arrested protoplasts. Several compounds known to support microtubule assembly in vitro were tested for their ability to promote microtubule assembly in vivo. Best results were obtained by addition of dimethyl sulfoxide to the culture medium. Unlimited amounts of callus could be produced with the dimethyl sulfoxide method from protoplasts which never developed a single callus in control experiments. 30 references, 3 figures.

  4. Apratoxin H and Apratoxin A Sulfoxide from the Red Sea Cyanobacterium Moorea producens

    PubMed Central

    Thornburg, Christopher C.; Cowley, Elise S.; Sikorska, Justyna; Shaala, Lamiaa A.; Ishmael, Jane E.; Youssef, Diaa T.A.; McPhail, Kerry L.

    2014-01-01

    Cultivation of the marine cyanobacterium Moorea producens, collected from the Nabq Mangroves in the Gulf of Aqaba (Red Sea), led to the isolation of new apratoxin analogues, apratoxin H (1) and apratoxin A sulfoxide (2), together with the known apratoxins A-C, lyngbyabellin B and hectochlorin. The absolute configuration of these new potent cytotoxins was determined by chemical degradation, MS, NMR, and CD spectroscopy. Apratoxin H (1) contains pipecolic acid in place of the proline residue present in apratoxin A, expanding the known suite of naturally occurring analogues that display amino acid substitutions within the final module of the apratoxin biosynthetic pathway. The oxidation site of apratoxin A sulfoxide (2) was deduced from MS fragmentation patterns and IR data, and 2 could not be generated experimentally by oxidation of apratoxin A. The cytotoxicity of 1 and 2 to human NCI-H460 lung cancer cells (IC50 = 3.4 and 89.9 nM, respectively) provides further insight into the structure–activity relationships in the apratoxin series. Phylogenetic analysis of the apratoxin-producing cyanobacterial strains belonging to the genus Moorea, coupled with the recently annotated apratoxin biosynthetic pathway, supports the notion that apratoxin production and structural diversity may be specific to their geographical niche. PMID:24016099

  5. Evidence for the dimerization-mediated catalysis of methionine sulfoxide reductase A from Clostridium oremlandii.

    PubMed

    Lee, Eun Hye; Lee, Kitaik; Kwak, Geun-Hee; Park, Yeon Seung; Lee, Kong-Joo; Hwang, Kwang Yeon; Kim, Hwa-Young

    2015-01-01

    Clostridium oremlandii MsrA (CoMsrA) is a natively selenocysteine-containing methionine-S-sulfoxide reductase and classified into a 1-Cys type MsrA. CoMsrA exists as a monomer in solution. Herein, we report evidence that CoMsrA can undergo homodimerization during catalysis. The monomeric CoMsrA dimerizes in the presence of its substrate methionine sulfoxide via an intermolecular disulfide bond between catalytic Cys16 residues. The dimeric CoMsrA is resolved by the reductant glutaredoxin, suggesting the relevance of dimerization in catalysis. The dimerization reaction occurs in a concentration- and time-dependent manner. In addition, the occurrence of homodimer formation in the native selenoprotein CoMsrA is confirmed. We also determine the crystal structure of the dimeric CoMsrA, having the dimer interface around the two catalytic Cys16 residues. A central cone-shaped hole is present in the surface model of dimeric structure, and the two Cys16 residues constitute the base of the hole. Collectively, our biochemical and structural analyses suggest a novel dimerization-mediated mechanism for CoMsrA catalysis that is additionally involved in CoMsrA regeneration by glutaredoxin.

  6. ENANTIOMER FRACTIONS OF CHLORDANE COMPOUNDS IN SEDIMENT SAMPLES FROM U.S. GEOLOGICAL SURVEY SITES IN LAKES, RIVERS, AND RESERVOIRS

    EPA Science Inventory

    More than 500 important environmental contaminants are chiral (having structures that are nonsuperimposible mirror images). Although enantiomer pairs have identical physical-chemical properties, their toxicity, biodegradation, and environmental fate often are different. Cyclo...

  7. Thermodynamics of the enantiomers of amino acid and monosaccharide binding to fullerenol used as an artificial sweet taste receptor model.

    PubMed

    Dong, Wen-Rui; Chen, Guo; Chen, Zhong-Xiu; Deng, Shao-Ping

    2013-12-01

    Fullerenol was used as sweet taste receptor model to investigate the binding affinities of structurally related pairs of enantiomers by isothermal titration calorimetry (ITC). It reveals that amino acid binding with fullerenol are enthalpy-cost and entropically-driven processes, whereas enthalpy contributes to monosaccharide binding to fullerenol. Spontaneous binding of amino acids was found through two sequential steps in which the sweeter enantiomer displays larger binding constants. Association of the d-form of fructose and l-form galactose with fullerenol suggested that, the higher the perceived sweetness intensity of the enantiomer, the larger was the binding constant with respect to their antipodes. Further investigation by molecular dynamic simulation showed that the binding energy and the perceived sweetness intensity were well correlated. The preliminary results of this biomimetic research cover the lack of information about the thermodynamic basis of sweet sensation and the underlying principles of sweetness differences between the enantiomers of amino acids and monosaccharides.

  8. ENANTIOMER SEPARATION OF POLYCHLORINATED BIPHENYL ATROPISOMERS AND POLYCHLORINATED BIPHENYL RETENTION BEHAVIOR ON MODIFIED CYCLODEXTRIN CAPILLARY GAS CHROMATOGRAPHY COLUMNS

    EPA Science Inventory

    Seven commercially-available chiral capillary gas chromatography columns containing modified cyclodextrins were evaluated for their ability to separate enantiomers of the 19 stable chiral polychlorinated biphenyl (PCB) atropisomers, and for their ability to separate these enantio...

  9. APPLICATION OF CYCLODEXTRIN-MODIFIED MICELLAR ELECTRONKINETIC CHROMATOGRAPHY TO THE SEPARATIONS OF SELECTED NEUTRAL PESTICIDES AND THEIR ENANTIOMERS

    EPA Science Inventory

    The environmental chemistry of chiral pesticides is receiving increased attention - enantiomeric ratios are being measured and enantioselective degradation processes are being reported. The requisite analysis involves separation of the various enantiomers. Mixtures of three class...

  10. Enantiomer-specific high-performance liquid chromatography with fluorescence detection of methamphetamines in abusers' hair and urine.

    PubMed

    Al-Dirbashi, O; Wada, M; Kuroda, N; Inuduka, S; Nakashima, K

    1999-12-01

    Enantiomer-specific high-performance liquid chromatography with fluorescence detection using 4-(4,5-diphenyl-1H-imidazol-2-yl)-benzoyl chloride as a fluorescence labeling reagent was applied to determine methamphetamine and its metabolites in abusers' hair and urine. Hair samples were segmentally analyzed based on 1 cm long segments. In four hair samples, only the S(+)-enantiomers of methamphetamine and its N-demethylated metabolite, S(+)-amphetamine were detected. Satisfactory correlation (r = 0.901) between the results of high-performance liquid chromatography-fluorescence and those of gas chromatography-nitrogen phosphorous detection was obtained (n = 19). In an abuser's urine sample, the S(+)- and R(-)-enantiomers of methamphetamine, amphetamine and para-hydroxymethamphetamine were detected. The degree of N-demethylation of S(+)-methamphetamine into the corresponding metabolite of amphetamine was significantly higher than that of the R(-)-enantiomer.

  11. Bioanalysis of the enantiomers of (+/-)-sarin using automated thermal cold-trap injection combined with two-dimensional gas chromatography.

    PubMed

    Spruit, H E; Trap, H C; Langenberg, J P; Benschop, H P

    2001-01-01

    A fully automated multidimensional gas chromatographic system with thermal desorption injection and alkali flame detection was developed for analysis of the enantiomers of the nerve agent (+/-)-sarin. The chiral stationary phase was CP Cyclodex B on which the sarin enantiomers were completely resolved. The absolute detection limit was 2.5 pg per enantiomer. The method is intended to be used for the analysis of the sarin enantiomers in biological samples. For this purpose, sarin was isolated from guinea pig blood via solid-phase extraction. Deuterated sarin was used as internal standard. Stabilization of sarin in the blood sample by acidification and addition of an excess of a competitive organophosphorus compound (neopentyl sarin) appeared to be essential. The absolute recovery of the extraction procedure was 60%, whereas the recovery relative to the internal standard was 100%.

  12. Three pairs of alkaloid enantiomers from the root of Isatis indigotica

    PubMed Central

    Liu, Yufeng; Wang, Xiaoliang; Chen, Minghua; Lin, Sheng; Li, Li; Shi, Jiangong

    2016-01-01

    Three pairs of enantiomerically pure alkaloids with diverse structure features, named isatindigoticoic acid A and epiisatindigoticoic acid A [(−)-1 and (+)-1], phaitanthrin A and epiphaitanthrin A [(−)-2 and (+)-2], and isatindopyrromizol A and epiisatindopyrromizol A [(−)-3 and (+)-3], respectively, were isolated from an aqueous extract of the roots of Isatis indigotica. Racemic and scalemic mixtures of these enantiomers were separated by HPLC on a chiral semi-preparative column. Their structures including absolute configurations were determined by extensive spectroscopic analysis in conjunction with the calculation of electronic circular dichroism (ECD) spectra. The enantiomer pairs possess parent structures of 2-oxo-1,2,3,4-tetrahydroquinoline-4-carboxylic acid, indolo[2,1-b]quinazolinone, and 3-thioxohexahydro-1H-pyrrolo[1,2-c]imidazol-1-one, respectively. Except for phaitanthrin A [(−)-2] which the configuration was previously undetermined, these compounds are new enantiomeric natural products. PMID:27006898

  13. Separation of phenylsuccinic acid enantiomers using biphasic chiral recognition high-speed countercurrent chromatography.

    PubMed

    Sun, Genlin; Tang, Kewen; Zhang, Panliang; Yang, Weijun; Sui, Guoqing

    2014-07-01

    High-speed countercurrent chromatography (HSCCC) combined with biphasic chiral recognition was successfully applied to the resolution of phenylsuccinic acid enantiomers. D-Isobutyl tartrate and hydroxypropyl-β-cyclodextrin were employed as lipophilic and hydrophilic selectors dissolved in the organic stationary phase and aqueous mobile phase, respectively. The two-phase solvent system was made up of n-hexane/methyl tert-butyl ether/water (0.5:1.5:2, v/v/v). Impacts of the type and concentration of chiral selectors, the pH value of the aqueous phase solution as well as the temperature on the separation efficiency were investigated. By means of preparative HSCCC, pure enantiomer was obtained by separating 810 mg of racemate with a purity >99.5% and a recovery rate between 82 and 85%. The experimental results indicate that biphasic recognition HSCCC provide a promising means for efficient separation of racemates.

  14. Simultaneous Chiral Separation of Flavanone, Naringenin, and Hesperetin Enantiomers by RP-UHPLC-DAD.

    PubMed

    Baranowska, Irena; Hejniak, Judyta; Magiera, Sylwia

    2016-02-01

    A rapid and effective RP-UHPLC-DAD method for enantioseparation of three flavanones, i.e., flavanone, naringenin, and hesperetin, was developed and validated. Chromatographic separation of the analytes was performed using a Chiralpak AD-3R analytical column under reverse phase conditions with methanol as the mobile phase. The method was validated in the concentration range of 0.2 to 50 µg/mL for enantiomers of flavanone and 0.5 to 50 µg/mL for enantiomers of naringenin and hesperetin. The limits of quantification were between 0.03 to 0.5 µg/mL. Intraday and interday precision were below 14% and accuracy varied from 0.04 to 8.17%.

  15. A high-performance liquid chromatographic assay for the enantiomers of bevantolol in human plasma.

    PubMed

    Rose, S E; Randinitis, E J

    1991-06-01

    A method was developed and validated for the simultaneous analysis of (+)- and (-)-bevantolol in human plasma. The assay involves plasma protein precipitation, derivatization of racemic bevantolol to its diastereomeric thioureas with 2,3,4,5-tetra-o-acetyl-alpha-D-glucopyranosyl isothiocyanate, and solid-phase extraction of the diastereomers from 0.5 ml human plasma. Chromatographic separation was accomplished under isocratic conditions using a reversed-phase C-18 analytical column and mobile phase consisting of equal parts of 75 mM dibasic ammonium phosphate buffer (adjusted to pH 3.5 with phosphoric acid) and acetonitrile, with a detection wavelength of 220 nm. The absolute peak-height method was employed for quantitation. Retention times for the diastereomers of (+)- and (-)-bevantolol were 7.4 and 6.4 min, respectively. The method is suitable for the quantification of the enantiomers over a concentration range of 40 to 800 ng/ml per enantiomer.

  16. Bubble fractionation of enantiomers from solution using molecularly imprinted polymers as collectors.

    PubMed

    Armstrong, D W; Schneiderheinze, J M; Hwang, Y S; Sellergren, B

    1998-09-01

    Adsorptive bubble separation methods have been used to enrich components from both heterogeneous and homogeneous solutions. These methods are particularly effective for processing large solution volumes at low cost. Previous work demonstrated that chiral, surface-active collectors could be used to enrich enantiomers from homogeneous solution in a foam fractionation process. In a significant extension of this work, the use of highly selective molecularly imprinted polymers (MIPs) and heterogeneous solutions for the bubble flotation of enantiomers was evaluated. The high selectivity and ease of recycling of the MIP make this a potentially powerful approach for process-scale separations from large-volume bulk solutions. New MIPs were produced with low swelling properties which allowed them to retain enantioselectivity after numerous recyclings.

  17. Pharmacokinetic study of ofloxacin enantiomers in Pagrosomus major by chiral HPLC.

    PubMed

    Nie, Jing; Wang, Yang-Guang; Gao, Xiao-Feng; OuYang, Xiao-Kun; Yang, Li-Ye; Yu, Di; Wu, Wei-Jian; Xu, Hong-Ping

    2016-03-01

    (S)-(-)-Ofloxacin and (R)-(+)-ofloxacin concentrations in the plasma of Pagrosomus major after drug treatment were detected by chiral high-performance liquid chromatography, and various pharmacokinetic parameters were calculated from these data. The elimination half-life of (S)-(-)-ofloxacin was significantly shorter than that of the (R)-(+) enantiomer. (S)-(-)-Ofloxacin also had a significantly lower maximum plasma concentration, area under the concentration-time curve from zero to infinity, and mean residence time than (R)-(+)-ofloxacin. However, the apparent volume of distribution and total body clearance of (S)-(-)-ofloxacin were greater than those of (R)-(+)-ofloxacin. The ratio of the (S)-(-)- to (R)-(+)-ofloxacin plasma concentration was always <1.0. Together, these data suggest that (S)-(-)-ofloxacin was preferentially excreted and (R)-(+)-ofloxacin was preferentially absorbed. Although the difference in pharmacokinetic parameters was small, the metabolic behavior of the ofloxacin enantiomers in P. major was enantioselective.

  18. Adsorption of ibuprofen enantiomers on a chiral stationary phase with a grafted antibiotic eremomycin

    NASA Astrophysics Data System (ADS)

    Reshetova, E. N.; Asnin, L. D.

    2015-02-01

    The adsorption of ibuprofen enantiomers on a chiral stationary phase Nautilus-E with a grafted antibiotic eremomycin from aqueous ethanol acetate buffer solutions was studied by chromatography. The ethanol concentration in the mobile phase was varied from 40 to 60 vol %. The adsorption isotherms of both enantiomers had a complex shape characterized by non-Langmuir type curvature and the presence of an inflection point. This is explained by two factors: the energy heterogeneity of the surface of the stationary phase and the dissociation of ibuprofen in the liquid phase. The effect of the system peak on the shape of the chromatograms of the target component was investigated. The temperature effect on the adsorption equilibrium was discussed.

  19. Supramolecular chiral host-guest nanoarchitecture induced by the selective assembly of barbituric acid derivative enantiomers.

    PubMed

    Sun, Xiaonan; Silly, Fabien; Maurel, Francois; Dong, Changzhi

    2016-10-21

    Barbituric acid derivatives are prochiral molecules, i.e. they are chiral upon adsorption on surfaces. Scanning tunneling microscopy reveals that barbituric acid derivatives self-assemble into a chiral guest-host supramolecular architecture at the solid-liquid interface on graphite. The host nanoarchitecture has a sophisticated wavy shape pattern and paired guest molecules are nested insides the cavities of the host structure. Each unit cell of the host structure is composed of both enantiomers with a ratio of 1:1. Furthermore, the wavy patterns of the nanoarchitecture are formed from alternative appearance of left- and right-handed chiral building blocks, which makes the network heterochiral. The functional guest-host nanoarchitecture is the result of two-dimensional chiral amplification from single enantiomers to organizational heterochiral supramolecular self-assembly. PMID:27623155

  20. Supramolecular chiral host-guest nanoarchitecture induced by the selective assembly of barbituric acid derivative enantiomers

    NASA Astrophysics Data System (ADS)

    Sun, Xiaonan; Silly, Fabien; Maurel, Francois; Dong, Changzhi

    2016-10-01

    Barbituric acid derivatives are prochiral molecules, i.e. they are chiral upon adsorption on surfaces. Scanning tunneling microscopy reveals that barbituric acid derivatives self-assemble into a chiral guest-host supramolecular architecture at the solid-liquid interface on graphite. The host nanoarchitecture has a sophisticated wavy shape pattern and paired guest molecules are nested insides the cavities of the host structure. Each unit cell of the host structure is composed of both enantiomers with a ratio of 1:1. Furthermore, the wavy patterns of the nanoarchitecture are formed from alternative appearance of left- and right-handed chiral building blocks, which makes the network heterochiral. The functional guest-host nanoarchitecture is the result of two-dimensional chiral amplification from single enantiomers to organizational heterochiral supramolecular self-assembly.

  1. Optimization and validation of a new CE method for the determination of pantoprazole enantiomers.

    PubMed

    Guan, Jin; Yan, Feng; Shi, Shuang; Wang, Silin

    2012-06-01

    A new CE method using sulfobutylether-beta-cyclodextrin (SBE-beta-CD) as chiral additive was developed and validated for the determination of pantoprazole enantiomers. The primary factors affecting its separation efficiency, which include chiral selector, buffer pH, organic additive, and applied voltage, were optimized. The best results were obtained using a buffer consisting of 50 mM borax-150 mM phosphate adjusted to pH 6.5, 20 mg/mL SBE-beta-CD, and a 10 kV applied voltage. The optimized method was validated for linearity, precision, accuracy, and proved to be robust. The LOD and LOQ for R-(+)-pantoprazole were 0.9 and 2.5 μg/mL, respectively. The method is capable of determining a minimum limit of 0.1% (w/w) of R-enantiomer in S-(-)-pantoprazole bulk samples. PMID:22736366

  2. Dosimetry of D- and L-enantiomers of /sup 11/C-labeled tryptophan and valine

    SciTech Connect

    Washburn, L.C.; Byrd, B.L.; Sun, T.T.; Crook, J.E.; Hubner, K.F.; Coffey, J.L.; Watson, E.E.

    1985-01-01

    We have previously reported the radiation dosimetry of /sup 11/C-labeled DL-tryptophan and DL-valine, as well as clinical pancreatic imaging studies with these agents. Because of significant uptake in both normal pancreas and in pancreatic tumors (thought to be due to the presence of the D-enantiomer), differential diagnosis of pancreatic carcinoma was not feasible. High-performance liquid chromatographic (HPLC) methods were developed for rapid resolution of /sup 11/C-labeled DL-tryptophan and DL-valine. Radiation dose estimates to the various organs in man were calculated for the D- and L-enantiomers of /sup 11/C-labeled tryptophan and valine, based on tissue distribution data in rats. The dose estimates were sufficiently low that 20-mCi doses of each of the enantiomeric amino acids were approved by the FDA for intravenous administration to humans. 21 refs., 3 tabs.

  3. NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo

    PubMed Central

    Eriksen, Jason L.; Sagi, Sarah A.; Smith, Tawnya E.; Weggen, Sascha; Das, Pritam; McLendon, D.C.; Ozols, Victor V.; Jessing, Kevin W.; Zavitz, Kenton H.; Koo, Edward H.; Golde, Todd E.

    2003-01-01

    Epidemiologic studies demonstrate that long-term use of NSAIDs is associated with a reduced risk for the development of Alzheimer disease (AD). In this study, 20 commonly used NSAIDs, dapsone, and enantiomers of flurbiprofen were analyzed for their ability to lower the level of the 42-amino-acid form of amyloid β protein (Aβ42) in a human H4 cell line. Thirteen of the NSAIDs and the enantiomers of flurbiprofen were then tested in acute dosing studies in amyloid β protein precursor (APP) transgenic mice, and plasma and brain levels of Aβ and the drug were evaluated. These studies show that (a) eight FDA-approved NSAIDs lower Aβ42 in vivo, (b) the ability of an NSAID to lower Aβ42 levels in cell culture is highly predicative of its in vivo activity, (c) in vivo Aβ42 lowering in mice occurs at drug levels achievable in humans, and (d) there is a significant correlation between Aβ42 lowering and levels of ibuprofen. Importantly, flurbiprofen and its enantiomers selectively lower Aβ42 levels in broken cell γ-secretase assays, indicating that these compounds directly target the γ-secretase complex that generates Aβ from APP. Of the compounds tested, meclofenamic acid, racemic flurbiprofen, and the purified R and S enantiomers of flurbiprofen lowered Aβ42 levels to the greatest extent. Because R-flurbiprofen reduces Aβ42 levels by targeting γ-secretase and has reduced side effects related to inhibition of cyclooxygenase (COX), it is an excellent candidate for clinical testing as an Aβ42 lowering agent. PMID:12897211

  4. Effects of flurbiprofen enantiomers on pain-related chemo-somatosensory evoked potentials in human subjects.

    PubMed Central

    Lötsch, J; Geisslinger, G; Mohammadian, P; Brune, K; Kobal, G

    1995-01-01

    1. The aim of the study was to investigate the analgesic effects of flurbiprofen enantiomers using an experimental pain model based on both chemo-somatosensory event-related potentials (CSSERP) and subjective pain ratings. 2. Healthy female volunteers (n = 16, age 23-36 years) participated in a placebo-controlled, randomised, double-blind, four-way crossover study. Single doses of (S)-flurbiprofen (50 mg), (R)-flurbiprofen (50 and 100 mg) and placebo were administered orally. Measurements were taken before and 2 h after administration of the medications. During each measurement, 32 painful stimuli of gaseous carbon dioxide (200 ms duration, interval approximately 30 s) of two concentrations (60 and 65% CO2 v/v) were applied to the right nostril. EEG was recorded from five positions and CSSERP were obtained in response to the painful CO2- stimuli. Additionally, subjects rated the perceived intensity of the painful stimuli by means of a visual analogue scale (VAS). 3. The CSSERP-amplitude P2, a measure of analgesic effect, decreased after administration of both (R)- and (S)-flurbiprofen, while it increased after placebo. This was statistically significant at recording positions C4 (P < 0.01) and Fz (P < 0.05). The analgesia-related decreases in evoked potential produced by (R)-flurbiprofen were dose-dependent. Comparing similar doses of (R)- and (S)-flurbiprofen, the decrease in CSSERP-amplitudes produced by the (S)-enantiomer was somewhat more pronounced, indicating a higher analgesic potency. 4. The present data indicate that both enantiomers of flurbiprofen produce analgesic effects. Since (R)-flurbiprofen caused only little toxicity in rats as compared with the (S)-enantiomer or the racemic compound, a reduction of the quantitatively most important side effects in the gastrointestinal tract might be achieved by employing (R)-flurbiprofen in pain therapy. PMID:8554936

  5. Thermodynamic study of an unusual chiral separation. Propranolol enantiomers on an immobilized cellulase

    SciTech Connect

    Fornstedt, T.; Sajonz, P.; Guiochon, G. |

    1997-02-12

    The thermodynamics of interaction of (R)- and (S)-propranolol between an acetic acid buffer (pH = 4.7 and 5.5) and the protein cellobiohydrolase I immobilized on silica gel was studied between 5 and 45{degree}C. The equilibrium data were fitted to a biLangmuir adsorption isotherm with excellent agreement. One of the two Langmuir contributions is the same for both enantiomers and accounts for the nonspecific interactions between these compounds and most sites on the surfaces (type-I, nonselective sites). It has a large saturation capacity. The second contribution accounts for the chiral selective interactions (type-II sites). It has a lower monolayer capacity than the first. The interaction enthalpy and entropy on type-I sites are -1.1 kcal/mol and +0.1 cal/(mol K), respectively. For type-II sites, they are -1.9 kcal/mol and -2.6 cal/(mol K), respectively, for (R)-propranolol and +1.6 kcal/mol and +11.6 cal/(mol K), respectively, for (S)-propranolol at pH = 5.5. This explains why at this pH the retention time of the less-retained R enantiomer decreases with increasing temperature, while the retention time of the S enantiomer increases, causing a large increase of the separation factor when the temperature is raised from 5 to 45{degree}C. The saturation capacity of the chiral contributions depends strongly on the pH, and the retention times of both enantiomers decrease with increasing temperature at pH = 4.7. 46 refs., 6 figs., 5 tabs.

  6. Effects of flurbiprofen enantiomers on pain-related chemo-somatosensory evoked potentials in human subjects.

    PubMed

    Lötsch, J; Geisslinger, G; Mohammadian, P; Brune, K; Kobal, G

    1995-10-01

    1. The aim of the study was to investigate the analgesic effects of flurbiprofen enantiomers using an experimental pain model based on both chemo-somatosensory event-related potentials (CSSERP) and subjective pain ratings. 2. Healthy female volunteers (n = 16, age 23-36 years) participated in a placebo-controlled, randomised, double-blind, four-way crossover study. Single doses of (S)-flurbiprofen (50 mg), (R)-flurbiprofen (50 and 100 mg) and placebo were administered orally. Measurements were taken before and 2 h after administration of the medications. During each measurement, 32 painful stimuli of gaseous carbon dioxide (200 ms duration, interval approximately 30 s) of two concentrations (60 and 65% CO2 v/v) were applied to the right nostril. EEG was recorded from five positions and CSSERP were obtained in response to the painful CO2- stimuli. Additionally, subjects rated the perceived intensity of the painful stimuli by means of a visual analogue scale (VAS). 3. The CSSERP-amplitude P2, a measure of analgesic effect, decreased after administration of both (R)- and (S)-flurbiprofen, while it increased after placebo. This was statistically significant at recording positions C4 (P < 0.01) and Fz (P < 0.05). The analgesia-related decreases in evoked potential produced by (R)-flurbiprofen were dose-dependent. Comparing similar doses of (R)- and (S)-flurbiprofen, the decrease in CSSERP-amplitudes produced by the (S)-enantiomer was somewhat more pronounced, indicating a higher analgesic potency. 4. The present data indicate that both enantiomers of flurbiprofen produce analgesic effects. Since (R)-flurbiprofen caused only little toxicity in rats as compared with the (S)-enantiomer or the racemic compound, a reduction of the quantitatively most important side effects in the gastrointestinal tract might be achieved by employing (R)-flurbiprofen in pain therapy.

  7. Separation of tryptophan enantiomers by ligand-exchange chromatography with novel chiral ionic liquids ligand.

    PubMed

    Qing, Haiqun; Jiang, Xinyu; Yu, Jingang

    2014-03-01

    Chiral ionic liquids (CILs) with amino acids as cations have been applied as novel chiral ligands coordinated with Cu(2+) to separate tryptophan enantiomers in ligand exchange chromatography. Four kinds of amino acid ionic liquids, including [L-Pro][CF3COO], [L-Pro][NO3], [L-Pro]2[SO4], and [L-Phe][CF3COO] were successfully synthesized and used for separation of tryptophan enantiomers. To optimize the separation conditions, [L-Pro][CF3COO] was selected as the model ligand. Some factors influencing the efficiency of chiral separation, such as copper ion concentration, CILs concentration, methanol ratio (methanol/H2O, v/v), and pH, were investigated. The obtained optimal separation conditions were as follows: 8.0 mmol/L Cu(OAc)2, 4.0 mmol/L [L-Pro][CF3COO], and 20% (v/v) methanol at pH 3.6. Under the optimum conditions, acceptable enantioseparation of tryptophan enantiomers could be observed with a resolution of 1.89. The results demonstrate the good applicability of CILs with amino acids as cations for chiral separation. Furthermore, a comparative study was also conducted for exploring the mechanism of the CILs as new ligands in ligand exchange chromatography.

  8. Structural and functional characterization of the enantiomers of the antischistosomal drug oxamniquine

    SciTech Connect

    Taylor, Alexander B.; Pica-Mattoccia, Livia; Polcaro, Chiara M.; Donati, Enrica; Cao, Xiaohang; Basso, Annalisa; Guidi, Alessandra; Rugel, Anastasia R.; Holloway, Stephen P.; Anderson, Timothy J.C.; Hart, P. John; Cioli, Donato; LoVerde, Philip T.

    2015-10-20

    For over two decades, a racemic mixture of oxamniquine (OXA) was administered to patients infected by Schistosoma mansoni, but whether one or both enantiomers exert antischistosomal activity was unknown. Recently, a ~30 kDa S. mansoni sulfotransferase (SmSULT) was identified as the target of OXA action. Here, we separate the OXA enantiomers using chromatographic methods and assign their optical activities as dextrorotary [(+)-OXA] or levorotary [(-)-OXA]. Crystal structures of the parasite enzyme in complex with optically pure (+)-OXA and (-)-OXA) reveal their absolute configurations as S- and R-, respectively. When tested in vitro, S-OXA demonstrated the bulk of schistosomicidal activity, while R-OXA had antischistosomal effects when present at relatively high concentrations. Crystal structures R-OXA•SmSULT and S-OXA•SmSULT complexes reveal similarities in the modes of OXA binding, but only the S-OXA enantiomer is observed in the structure of the enzyme exposed to racemic OXA. Together the data suggest the higher schistosomicidal activity of S-OXA is correlated with its ability to outcompete R-OXA binding the sulfotransferase active site. In conclusion, these findings have important implications for the design, syntheses, and dosing of new OXA-based antischistosomal compounds.

  9. Structural and functional characterization of the enantiomers of the antischistosomal drug oxamniquine

    DOE PAGES

    Taylor, Alexander B.; Pica-Mattoccia, Livia; Polcaro, Chiara M.; Donati, Enrica; Cao, Xiaohang; Basso, Annalisa; Guidi, Alessandra; Rugel, Anastasia R.; Holloway, Stephen P.; Anderson, Timothy J.C.; et al

    2015-10-20

    For over two decades, a racemic mixture of oxamniquine (OXA) was administered to patients infected by Schistosoma mansoni, but whether one or both enantiomers exert antischistosomal activity was unknown. Recently, a ~30 kDa S. mansoni sulfotransferase (SmSULT) was identified as the target of OXA action. Here, we separate the OXA enantiomers using chromatographic methods and assign their optical activities as dextrorotary [(+)-OXA] or levorotary [(-)-OXA]. Crystal structures of the parasite enzyme in complex with optically pure (+)-OXA and (-)-OXA) reveal their absolute configurations as S- and R-, respectively. When tested in vitro, S-OXA demonstrated the bulk of schistosomicidal activity, whilemore » R-OXA had antischistosomal effects when present at relatively high concentrations. Crystal structures R-OXA•SmSULT and S-OXA•SmSULT complexes reveal similarities in the modes of OXA binding, but only the S-OXA enantiomer is observed in the structure of the enzyme exposed to racemic OXA. Together the data suggest the higher schistosomicidal activity of S-OXA is correlated with its ability to outcompete R-OXA binding the sulfotransferase active site. In conclusion, these findings have important implications for the design, syntheses, and dosing of new OXA-based antischistosomal compounds.« less

  10. Structural and Functional Characterization of the Enantiomers of the Antischistosomal Drug Oxamniquine

    PubMed Central

    Polcaro, Chiara M.; Donati, Enrica; Cao, Xiaohang; Basso, Annalisa; Guidi, Alessandra; Rugel, Anastasia R.; Holloway, Stephen P.; Anderson, Timothy J. C.; Hart, P. John; Cioli, Donato; LoVerde, Philip T.

    2015-01-01

    Background For over two decades, a racemic mixture of oxamniquine (OXA) was administered to patients infected by Schistosoma mansoni, but whether one or both enantiomers exert antischistosomal activity was unknown. Recently, a ~30 kDa S. mansoni sulfotransferase (SmSULT) was identified as the target of OXA action. Methodology/Principal Findings Here, we separate the OXA enantiomers using chromatographic methods and assign their optical activities as dextrorotary [(+)-OXA] or levorotary [(-)-OXA]. Crystal structures of the parasite enzyme in complex with optically pure (+)-OXA and (-)-OXA) reveal their absolute configurations as S- and R-, respectively. When tested in vitro, S-OXA demonstrated the bulk of schistosomicidal activity, while R-OXA had antischistosomal effects when present at relatively high concentrations. Crystal structures R-OXA•SmSULT and S-OXA•SmSULT complexes reveal similarities in the modes of OXA binding, but only the S-OXA enantiomer is observed in the structure of the enzyme exposed to racemic OXA. Conclusions/Significance Together the data suggest the higher schistosomicidal activity of S-OXA is correlated with its ability to outcompete R-OXA binding the sulfotransferase active site. These findings have important implications for the design, syntheses, and dosing of new OXA-based antischistosomal compounds. PMID:26485649

  11. [Determination of doxazosin enantiomers in rat plasma and investigation of their chiral inversion].

    PubMed

    Zhen, Ya-Qin; Kong, De-Zhi; Li, Qing; Zhao, Jing; Ren, Lei-Ming

    2013-06-01

    The study is to establish an HPLC method using fluorescence detector for the determination of doxazosin enantiomers and investigate their chiral inversion in vitro and in vivo. Ultron ES-OVM was taken as the chiral chromatographic column, and the column temperature was 30 degrees C. Isocratic elution using a mobile phase of phosphate buffer-acetonitrile (85 : 15, v/v) at a flow rate of 0.8 mL x min(-1) was done. The fluorescence detection was set at lambda(Ex) = 255 nm and lambda(Em) = 385 nm. Prazosin was used as the internal standard. (-) Doxazosin or (+) doxazosin added into rat plasma in vitro was determined after incubating in 37 degrees C water bath for 2, 5 and 10 days. (-) Doxazosin or (+) doxazosin was administered orally to the rats for one months. Plasma samples were taken at 8 h after the last administration. A good linear relationship was achieved when the concentration of doxazosin enantiomers was within the range of 4 - 2 000 ng x mL(-1). The average recovery for (-) doxazosin was 99.5% with RSD 3.6%, and for (+) doxazosin was 99.3% with RSD 4.3%. Chiral inversion was observed neither in vitro nor in vivo studies. The method is selective, accurate and reproducible, which is suitable for the detection of doxazosin enantiomers in rat plasma. The in vitro and in vivo studies indicate that chiral inversion occurs uneasily between (-) doxazosin and (+) doxazosin in the rat.

  12. [Chromatographic separation of aminoglutethimide enantiomers on cellulose tris(3,5-dimethylphenylcarbamate) chiral stationary phase].

    PubMed

    Lin, Xiaoiian; Gong, Rujin; Li, Ping; Yu, Jianguo

    2014-08-01

    Aminoglutethimide (AG) has been used clinically as a drug in the treatment of hormone-dependent metastatic breast cancer. It was reported that S-(-)-AG enantiomer had small activity and sometimes might cause side effects. Therefore, it was of great significance to obtain the high-purity R-(+)-AG by enantioseparation. In this work, aminoglutethimide enantiomers were separated by high performance liquid chromatography (HPLC) using an analytical column which was packed with cellulose tris(3,5-dimethylphenylcarbamate) stationary phase (Chiralcel OD-H). The solubilities of racemic AG in two different solvent compositions, n-hexane/ethanol and n-hexane/isopropanol, were measured, separately. The effects of alcohol content and monoethanolamine additive on the separation performance of racemic AG by HPLC were investigated. According to the experiments, n-hexane-ethanol (30:70, v/v) with 0.1% monoethanolamine additive was selected as the mobile phase. The separation factor, resolution, asymmetry factor, number of theoretical plates and maximum column capacity were measured and analyzed for the chromatographic separation of racemic AG at a flow-rate of 0. 6 mL/min and column temperature of 25-40 °C, with Chiralcel OD-H as stationary phase and n-hexane-ethanol (30:70, v/v) with 0. 1% monoethanolamine as mobile phase. This work provides the basic information of chromatographic separation for the batch and continuous production of aminoglutethimide enantiomers.

  13. A simpler and faster capillary electrophoresis method for determination of mianserin enantiomers in human serum.

    PubMed

    Grodner, Błazej; Pachecka, Jan

    2006-01-01

    A stereospecific sample stacking capillary zone electrophoresis method is described for determination of S(+) and R(-) enantiomers of mianserin (1,2,3,4,10,14b-hexahydro-2-methyldibenzo[c,f]pyrazino[1,2-a]azepine) in human serum. The enantiomers of mianserin were extracted from human serum in one step extraction procedure using the mixture n-heptane:ethyl acetate (80:20, v/v). After separation of layers and freezing at -28 degrees C the organic layer was decanted and evaporated under a stream of nitrogen. The sample was dissolved in the mixture: water:methanol:acetonitrile (2:1:1, v/v/v). Separation was conducted in an aqueous solution of phosphoric acid (0.075M) adjusted to pH = 3.0 with concentrated triethylamine, and 2 mmole/L of 2-hydroxypropyl-beta-cyclodextrin. The analytes were measured by ultraviolet detection at 214 nm after separation on a Fused-Silica eCAP capillary. Clozapine was used as an internal standard. Recovery of the enantiomers from serum ranged from 82.94 to 90.37%. Total time of analysis was 49 minutes, whereas the other methods needed up to 100 minutes.

  14. Stereoselective pharmacokinetics and interconversions of flosequinan enantiomers containing chiral sulphoxide in rat.

    PubMed

    Kashiyama, E; Todaka, T; Odomi, M; Tanokura, Y; Johnson, D B; Yokoi, T; Kamataki, T; Shimizu, T

    1994-04-01

    1. In order to study the pharmacokinetics of flosequinan enantiomers ((+-)-7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone) containing chiral sulphur, plasma levels of (+)-(R)- and (-)-(S)-flosequinan (R-FSO and S-FSO) and two metabolites (flosequinan sulphide (FS) and flosequinan sulphone (FSO2)) were measured after oral and i.v. administration of racemic flosequinan (rac-FSO), R-FSO and S-FSO in male rat. 2. The pharmacokinetic parameters of the enantiomers were different after oral and i.v. administration of R-FSO and S-FSO. The plasma clearance of R-FSO was higher than S-FSO. 3. The major metabolites of boh R-FSO and S-FSO was FSO2. A minor metabolite, FS, was also detected in plasma. 4. Interconversions occurred after the oral and i.v. administration of R-FSO and S-FSO. The amount of interconversion from S-FSO and R-FSO was greater than that from R-FSO to S-FSO. The rate of interconversion after oral administration was higher than that after i.v. administration. 5. After i.v. administration of FS, R-FSO and S-FSO were detected in plasma, suggesting that the interconversion occurred via formation of FS. 6. The pharmacokinetic parameters of R-FSO after administration of rac-FSO differed from that after administration of R-FSO, indicating the interaction between each enantiomer.

  15. Enantioselective phytotoxicity and bioacitivity of the enantiomers of the herbicide napropamide.

    PubMed

    Qi, Yanli; Liu, Donghui; Zhao, Wenting; Liu, Chang; Zhou, Zhiqiang; Wang, Peng

    2015-11-01

    Enantioselectivity of chiral pesticide enantiomers should be taken into consideration in pesticide application and environmental risk assessment. The phytotoxicity of the enantiomers of napropamide to cucumber, soybean, and the bioactivity to the target weeds Poa annua and Festuca arundinacea have been studied in this work. To the nontarget crops, the influences of napropamide on the root, shoot, fresh weight, chlorophyll, superoxide dismutase (SOD) and catalase (CAT) activities and membrane lipid peroxides have been studied. (-)-Napropamide was more toxic than the racemate and (+)-napropamide to soybean and cucumber in terms of root, shoot and fresh weight. The content of chlorophyll was not affected by napropamide. The impacts on the activities of SOD, CAT and membrane lipid peroxides showed that napropamide could induce the oxidative stress and rac-napropamide caused a stronger oxidative damage to cucumber and soybean than (-)-napropamide and (+)-napropamide. For the target weeds, the influences of napropamide on root, shoot and fresh weight have been studied. (-)-Napropamid was more active to P. annua, while rac-napropamide was more active to F. arundinacea. To reduce environmental pollution and improve the effectiveness of chiral pesticide, single enantiomer should be developed and produced. This work may provide evidence for developing optical pure product. PMID:26615149

  16. Tianeptine and its enantiomers: effects on spatial memory in rats with medial septum lesions.

    PubMed

    Morris, R G; Kelly, S; Burney, D; Anthony, T; Boyer, P A; Spedding, M

    2001-08-01

    Tianeptine, an atypical antidepressant that exhibits clinical efficacy in measures of depression and anxiety, has been reported to enhance learning and memory in rats under certain conditions, an effect not observed with other tricyclic antidepressants. The present study explores further the possibility that tianeptine or its enantiomers (S 16190 and S 16191) can enhance either learning or retention in animals in which the hippocampus has been made partially dysfunctional. The effects of tianeptine and its enantiomers were tested using an open field watermaze test, in rats with partial lesions of the medial septum/diagonal band of Broca (MSDB). When given to normal rats, tianeptine (10 mg/kg, i.p.) did not significantly affect learning as compared to animals injected with saline. We therefore created, in other animals, partial ibotenic acid lesions of MSDB and showed histochemically that these lesions reduced but did not abolish the density of acetylcholinesterase staining in the hippocampus. They impaired both the acquisition of place-navigation and the long-term retention of spatial information over 7 days. Against the baseline of impaired performance in animals with these lesions, neither tianeptine (10 mg/kg) nor its enantiomers (5 mg/kg) affected the rate of acquisition of place navigation. However, tianeptine did enhance the retention of spatial memory over 7 days. These results are discussed in relation to different effects that tianeptine may have on learning including its ability to block stress-induced dendritic re-modelling of the hippocampus.

  17. Toxicokinetic assessment of methylphenidate (Ritalin) enantiomers in pregnant rats and rabbits.

    PubMed

    Bakhtiar, Ray; Tse, Francis L S

    2004-06-01

    Ritalin or methylphenidate (MPH) is prescribed for the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. The present report describes the determination of plasma concentrations of D-threo- and L-threo-enantiomers of MPH in toxicokinetic (TK) studies in pregnant Wistar Hannover rats and New Zealand white rabbits following repeated daily oral dosing of D,L-MPH (racemate). A previously reported chiral liquid chromatography tandem mass spectrometric (LC-MS/MS) method with a lower limit of quantification (LLOQ) of 1.09 ng/mL was utilized. Oral (gavage) doses of 7, 25 and 75 mg/kg/day of racemic MPH were selected for the rat study. An over-proportional increase in exposure was observed with increasing doses of MPH racemate, the effect being more profound with the D- than the L-enantiomer. In contrast, Cmax values of both enantiomers were approximately proportional to the dose. Oral (gavage) doses of 20, 60 and 200 mg/kg were selected for the rabbit study. In general, for the D-isomer, an over-proportional increase in exposure was observed with increasing doses of MPH racemate. Conversely, for the L-isomer, a slight under-proportionality was detected in exposure with increasing doses of D,L-MPH. For mean Cmax, while L-isomer exhibited dose proportionality with increasing doses of MPH racemate, the D-isomer appeared to be over-proportional. Herein, the experimental design and observed TK parameters in each study are presented.

  18. [Effect of bolus administration of albendazole into the rumen on gastrointestinal nematodes and the Dicrocoelium dendriticum trematode in sheep].

    PubMed

    Corba, J; Krupicer, I; Várady, M; Pet'ko, B

    1994-01-01

    The efficacy of intraruminal albendazole (ABZ) capsules (Proftril-Captec) and the effect of treatment on productivity parameters were studied in two experiments totally on 466 ewes naturally infected with gastrointestinal nematodes and trematodes D. dendriticum. Ovoscopical tests revealed that treated animals remained negative during 10-12 weeks after the administration of capsules and that pasture contamination with helminths was significantly reduced. Necropsy revealed 96.9-99.2% efficacy against nematodes Nematodirus spp., Oesophagostomum spp., Cooperia spp., Trichostrongylus spp. and Trichuris ovis. Priority finding is the efficacy of ABZ capsules against trematodes D. dendriticum which was in the first experiment 88.5% and in the second experiment 91.8%. During the 6-month pasture season treated ewes produced on average 2.56 kg cheese and 0.6 kg wool per ewe more than untreated controls.

  19. Trichuris suis and Oesophagostomum dentatum Show Different Sensitivity and Accumulation of Fenbendazole, Albendazole and Levamisole In Vitro

    PubMed Central

    Hansen, Tina V. A.; Nejsum, Peter; Friis, Christian; Olsen, Annette; Thamsborg, Stig Milan

    2014-01-01

    Background The single-dose benzimidazoles used against Trichuris trichiura infections in humans are not satisfactory. Likewise, the benzimidazole, fenbendazole, has varied efficacy against Trichuris suis whereas Oesophagostomum dentatum is highly sensitive to the drug. The reasons for low treatment efficacy of Trichuris spp. infections are not known. Methodology We studied the effect of fenbendazole, albendazole and levamisole on the motility of T. suis and O. dentatum and measured concentrations of the parent drug compounds and metabolites of the benzimidazoles within worms in vitro. The motility and concentrations of drug compounds within worms were compared between species and the maximum specific binding capacity (Bmax) of T. suis and O. dentatum towards the benzimidazoles was estimated. Comparisons of drug uptake in living and killed worms were made for both species. Principal findings The motility of T. suis was generally less decreased than the motility of O. dentatum when incubated in benzimidazoles, but was more decreased when incubated in levamisole. The Bmax were significantly lower for T. suis (106.6, and 612.7 pmol/mg dry worm tissue) than O. dentatum (395.2, 958.1 pmol/mg dry worm tissue) when incubated for 72 hours in fenbendazole and albendazole respectively. The total drug concentrations (pmol/mg dry worm tissue) were significantly lower within T. suis than O. dentatum whether killed or alive when incubated in all tested drugs (except in living worms exposed to fenbendazole). Relatively high proportions of the anthelmintic inactive metabolite fenbendazole sulphone was measured within T. suis (6–17.2%) as compared to O. dentatum (0.8–0.9%). Conclusion/Significance The general lower sensitivity of T. suis towards BZs in vitro seems to be related to a lower drug uptake. Furthermore, the relatively high occurrence of fenbendazole sulphone suggests a higher detoxifying capacity of T. suis as compared to O. dentatum. PMID:24699263

  20. Inhibition of Ammonia Oxidation in Nitrosomonas europaea by Sulfur Compounds: Thioethers Are Oxidized to Sulfoxides by Ammonia Monooxygenase

    PubMed Central

    Juliette, Lisa Y.; Hyman, Michael R.; Arp, Daniel J.

    1993-01-01

    Organic sulfur compounds are well-known nitrification inhibitors. The inhibitory effects of dimethylsulfide, dimethyldisulfide, and ethanethiol on ammonia oxidation by Nitrosomonas europaea were examined. Both dimethylsulfide and dimethyldisulfide were weak inhibitors of ammonia oxidation and exhibited inhibitory characteristics typical of substrates for ammonia monooxygenase (AMO). Depletion of dimethylsulfide required O2 and was prevented with either acetylene or allylthiourea, two inhibitors of AMO. The inhibition of ammonia oxidation by dimethylsulfide was examined in detail. Cell suspensions incubated in the presence of ammonia oxidized dimethylsulfide to dimethyl sulfoxide. Depletion of six other thioethers was also prevented by treating cell suspensions with either allylthiourea or acetylene. The oxidative products of three thioethers were identified as the corresponding sulfoxides. The amount of sulfoxide formed accounted for a majority of the amount of sulfide depleted. By using gas chromatography coupled with mass spectrometry, allylmethylsulfide was shown to be oxidized to allylmethylsulfoxide by N. europaea with the incorporation of a single atom of 18O derived from 18O2 into the sulfide. This result supported our conclusion that a monooxygenase was involved in the oxidation of allylmethylsulfide. The thioethers are concluded to be a new class of substrates for AMO. This is the first report of the oxidation of the sulfur atom by AMO in whole cells of N. europaea. The ability of N. europaea to oxidize dimethylsulfide is not unique among the ammonia-oxidizing bacteria. Nitrosococcus oceanus, a marine nitrifier, was also demonstrated to oxidize dimethylsulfide to dimethyl sulfoxide. PMID:16349086

  1. Copper(I)-Catalyzed Asymmetric Pinacolboryl Addition of N-Boc-imines Using a Chiral Sulfoxide-Phosphine Ligand.

    PubMed

    Wang, Ding; Cao, Peng; Wang, Bing; Jia, Tao; Lou, Yazhou; Wang, Min; Liao, Jian

    2015-05-15

    Highly efficient and enantioselective copper(I)-catalyzed pinacolboryl addition of N-Boc-imines is reported. By using a single chiral sulfoxide-(dialkyl)phosphine (SOP) ligand, both enantiomeric isomers of α-amino boronic esters were obtained through an achiral counteranion switch. PMID:25906191

  2. Enantiopure 1,4-diols and 1,4-aminoalcohols via stereoselective acyclic sulfoxide-sulfenate rearrangement.

    PubMed

    Fernández de la Pradilla, Roberto; Colomer, Ignacio; Ureña, Mercedes; Viso, Alma

    2011-05-01

    Treatment of acyclic α-hydroxy and α-tosylamino sulfinyl dienes with amines affords enantiopure 1,4-diol or 1,4-hydroxysulfonamide derivatives in good yields and diastereoselectivities. This one-pot procedure entails a conjugate addition that triggers a diastereoselective sulfoxide-sulfenate [2,3]-sigmatropic rearrangement.

  3. Methionine sulfoxide reductase A affects β-amyloid solubility and mitochondrial function in a mouse model of Alzheimer's disease.

    PubMed

    Moskovitz, Jackob; Du, Fang; Bowman, Connor F; Yan, Shirley S

    2016-03-15

    Accumulation of oxidized proteins, and especially β-amyloid (Aβ), is thought to be one of the common causes of Alzheimer's disease (AD). The current studies determine the effect of an in vivo methionine sulfoxidation of Aβ through ablation of the methionine sulfoxide reductase A (MsrA) in a mouse model of AD, a mouse that overexpresses amyloid precursor protein (APP) and Aβ in neurons. Lack of MsrA fosters the formation of methionine sulfoxide in proteins, and thus its ablation in the AD-mouse model will increase the formation of methionine sulfoxide in Aβ. Indeed, the novel MsrA-deficient APP mice (APP(+)/MsrAKO) exhibited higher levels of soluble Aβ in brain compared with APP(+) mice. Furthermore, mitochondrial respiration and the activity of cytochrome c oxidase were compromised in the APP(+)/MsrAKO compared with control mice. These results suggest that lower MsrA activity modifies Aβ solubility properties and causes mitochondrial dysfunction, and augmenting its activity may be beneficial in delaying AD progression.

  4. Regulation of Selenoproteins and Methionine Sulfoxide Reductases A and B1 by Age, Calorie Restriction, and Dietary Selenium in Mice

    PubMed Central

    Novoselov, Sergey V.; Kim, Hwa-Young; Hua, Deame; Lee, Byung Cheon; Astle, Clinton M.; Harrison, David E.; Friguet, Bertrand; Moustafa, Mohamed E.; Carlson, Bradley A.; Hatfield, Dolph L.

    2010-01-01

    Abstract Methionine residues are susceptible to oxidation, but this damage may be reversed by methionine sulfoxide reductases MsrA and MsrB. Mammals contain one MsrA and three MsrBs, including a selenoprotein MsrB1. Here, we show that MsrB1 is the major methionine sulfoxide reductase in liver of mice and it is among the proteins that are most easily regulated by dietary selenium. MsrB1, but not MsrA activities, were reduced with age, and the selenium regulation of MsrB1 was preserved in the aging liver, suggesting that MsrB1 could account for the impaired methionine sulfoxide reduction in aging animals. We also examined regulation of Msr and selenoprotein expression by a combination of dietary selenium and calorie restriction and found that, under calorie restriction conditions, selenium regulation was preserved. In addition, mice overexpressing a mutant form of selenocysteine tRNA reduced MsrB1 activity to the level observed in selenium deficiency, whereas MsrA activity was elevated in these animals. Finally, we show that selenium regulation in inbred mouse strains is preserved in an outbred aging model. Taken together, these findings better define dietary regulation of methionine sulfoxide reduction and selenoprotein expression in mice with regard to age, calorie restriction, dietary Se, and a combination of these factors. Antioxid. Redox Signal. 12, 829–838. PMID:19769460

  5. Preferential solvation of lysozyme in dimethyl sulfoxide/water binary mixture probed by terahertz spectroscopy.

    PubMed

    Das, Dipak Kumar; Patra, Animesh; Mitra, Rajib Kumar

    2016-09-01

    We report the changes in the hydration dynamics around a model protein hen egg white lysozyme (HEWL) in water-dimethyl sulfoxide (DMSO) binary mixture using THz time domain spectroscopy (TTDS) technique. DMSO molecules get preferentially solvated at the protein surface, as indicated by circular dichroism (CD) and Fourier transform infrared (FTIR) study in the mid-infrared region, resulting in a conformational change in the protein, which consequently modifies the associated hydration dynamics. As a control we also study the collective hydration dynamics of water-DMSO binary mixture and it is found that it follows a non-ideal behavior owing to the formation of DMSO-water clusters. It is observed that the cooperative dynamics of water at the protein surface does follow the DMSO-mediated conformational modulation of the protein. PMID:27372901

  6. Strong intermolecular exciton couplings in solid-state circular dichroism of aryl benzyl sulfoxides.

    PubMed

    Padula, Daniele; Di Pietro, Sebastiano; Capozzi, Maria Annunziata M; Cardellicchio, Cosimo; Pescitelli, Gennaro

    2014-09-01

    A series of 13 enantiopure aryl benzyl sulfoxides () with different substituents on the two aromatic rings has been previously analyzed by means of electronic circular dichroism (CD) spectroscopy. Most of these compounds are crystalline and their X-ray structure is established. For almost one-half of the series, CD spectra measured in the solid state were quite different from those in acetonitrile solution. We demonstrate that the difference is due to strong exciton couplings between molecules packed closely together in the crystal. The computational approach consists of time-dependent density functional theory (TDDFT) calculations run on "dimers" composed of nearest neighbors found in the lattice. Solid-state CD spectra are well reproduced by the average of all possible pairwise terms. The relation between the crystal space group and conformation, and the appearance of solid-state CD spectra, is also discussed.

  7. Onychomycosis treated with a dilute povidone–iodine/dimethyl sulfoxide preparation

    PubMed Central

    Capriotti, Kara; Capriotti, Joseph A

    2015-01-01

    Background Povidone–iodine (PVP-I) 10% aqueous solution is a well-known, nontoxic, commonly used topical antiseptic with no reported incidence of fungal resistance. We have been using a low-dose formulation of 1% PVP-I (w/w) in a solution containing dimethyl sulfoxide (DMSO) in our clinical practice for a variety of indications. Presented here is our clinical experience with this novel formulation in a severe case of onychomycosis that was resistant to any other treatment. Findings A 49-year-old woman who had been suffering from severe onychomycosis for years presented after failing to find any remedy including over the counter (OTC), topical, and systemic oral prescribed therapies. Conclusion The topical povidone–iodine/DMSO system was very effective in this case at alleviating the signs and symptoms of onychomycosis. This novel combination warrants further investigation in randomized, controlled trials to further elucidate its clinical utility. PMID:26491374

  8. A protective role of methionine-R-sulfoxide reductase against cadmium in Schizosaccharomyces pombe.

    PubMed

    Lim, Chang-Jin; Jo, Hannah; Kim, Kyunghoon

    2014-11-01

    The Schizosaccharomyces pombe cells harboring the methionine- R-sulfoxide reductase (MsrB)-overexpressing recombinant plasmid pFMetSO exhibited better growth than vector control cells, when shifted into fresh medium containing cadmium chloride (abbreviated as Cd). Although both groups of cells contained enhanced reactive oxygen species (ROS) and nitric oxide (NO) levels in the presence of Cd, ROS and NO levels were significantly lower in the S. pombe cells harboring pFMetSO than in vector control cells. Conversely, the S. pombe cells harboring pFMetSO possessed higher total glutathione (GSH) levels and a greater reduced/oxidized GSH ratio than vector control cells under the same conditions.

  9. Electrical conductivity of solutions of copper(II) nitrate crystalohydrate in dimethyl sulfoxide

    NASA Astrophysics Data System (ADS)

    Mamyrbekova, Aigul K.; Mamitova, A. D.; Mamyrbekova, Aizhan K.

    2016-06-01

    Conductometry is used to investigate the electric conductivity of Cu(NO3)2 ṡ 3H2O solutions in dimethyl sulfoxide in the 0.01-2.82 M range of concentrations and at temperatures of 288-318 K. The limiting molar conductivity of the electrolyte and the mobility of Cu2+ and NO 3 - ions, the effective coefficients of diffusion of copper(II) ions and nitrate ions, and the degree and constant of electrolytic dissociation are calculated for different temperatures from the experimental results. It is established that solutions containing 0.1-0.6 M copper nitrate trihydrate in DMSO having low viscosity and high electrical conductivity can be used in electrochemical deposition.

  10. Methionine sulfoxide reductase A protects neuronal cells against brief hypoxia/reoxygenation

    NASA Astrophysics Data System (ADS)

    Yermolaieva, Olena; Xu, Rong; Schinstock, Carrie; Brot, Nathan; Weissbach, Herbert; Heinemann, Stefan H.; Hoshi, Toshinori

    2004-02-01

    Hypoxia/reoxygenation induces cellular injury by promoting oxidative stress. Reversible oxidation of methionine in proteins involving the enzyme peptide methionine sulfoxide reductase type A (MSRA) is postulated to serve a general antioxidant role. Therefore, we examined whether overexpression of MSRA protected cells from hypoxia/reoxygenation injury. Brief hypoxia increased the intracellular reactive oxygen species (ROS) level in PC12 cells and promoted apoptotic cell death. Adenovirus-mediated overexpression of MSRA significantly diminished the hypoxia-induced increase in ROS and facilitated cell survival. Measurements of the membrane potentials of intact mitochondria in PC12 cells and of isolated rat liver mitochondria showed that hypoxia induced depolarization of the mitochondrial membrane. The results demonstrate that MSRA plays a protective role against hypoxia/reoxygenation-induced cell injury and suggest the therapeutic potential of MSRA in ischemic heart and brain disease.

  11. Dimethyl sulfoxide as a mild oxidizing agent for porous silicon and its effect on photoluminescence

    SciTech Connect

    Song, J.H.; Sailor, M.J.

    1998-06-29

    Dimethyl sulfoxide acts as a mild room-temperature oxidant of luminescent porous silicon. The oxidation reaction is accompanied by a loss in photoluminescence intensity from the silicon nanocrystallites, indicating that the oxide formed under these conditions is electronically defective. The rate of oxidation is reduced if the reaction is carried out in the presence of the radical traps 2,6-di-tert-butyl-4-methylphenol (butylated hydroxytoluene, BHT) or cumene. In addition, photoluminescence intensity is preserved if the DMSO oxidation reaction is carried out in the presence of high concentrations of BHT. The BHT is proposed to form a more electronically passive oxide layer by hydrogenating the surface radicals (dangling bonds) generated during the oxidation reaction.

  12. Inactivation kinetics of polyphenol oxidase from pupae of blowfly (Sarcophaga bullata) in the dimethyl sulfoxide solution.

    PubMed

    Chen, Chao-Qi; Li, Zhi-Cong; Pan, Zhi-Zhen; Zhu, Yu-Jing; Yan, Ruo-Rong; Wang, Qin; Yan, Jiang-Hua; Chen, Qing-Xi

    2010-04-01

    The effects of dimethyl sulfoxide (DMSO) on the activity of polyphenol oxidase (PPO, EC 1.14.18.1) from blowfly pupae for the oxidation of L-3,4-dihydroxyphenylalanine were studied. The results showed that low concentrations of DMSO could lead to reversible inactivation to the enzyme. The IC(50) value, the inactivator concentration leading to 50% activity lost, was estimated to be 2.35 M. Inactivation of the enzyme by DMSO was classified as mixed type. The kinetics of inactivation of PPO from blowfly pupae in the low concentrations of DMSO solution was studied using the kinetic method of the substrate reaction. The rate constants of inactivation were determined. The results show that k(+0) was much larger than k'(+0), indicating that the free enzyme molecule was more fragile than the enzyme-substrate complex in the DMSO solution. It was suggested that the presence of the substrate offers marked protection of this enzyme against inactivation by DMSO.

  13. Membrane permeability of the human granulocyte to water, dimethyl sulfoxide, glycerol, propylene glycol and ethylene glycol

    PubMed Central

    Vian, Alex M.; Higgins, Adam Z.

    2015-01-01

    Granulocytes are currently transfused as soon as possible after collection because they rapidly deteriorate after being removed from the body. This short shelf life complicates the logistics of granulocyte collection, banking and safety testing. Cryopreservation has the potential to significantly increase shelf life; however, cryopreservation of granulocytes has proven to be difficult. In this study, we investigate the membrane permeability properties of human granulocytes, with the ultimate goal of using membrane transport modeling to facilitate development of improved cryopreservation methods. We first measured the equilibrium volume of human granulocytes in a range of hypo- and hypertonic solutions and fit the resulting data using a Boyle-van't Hoff model. This yielded an isotonic cell volume of 378 μm3 and an osmotically inactive volume of 165 μm3. To determine the permeability of the granulocyte membrane to water and cryoprotectant (CPA), cells were injected into well-mixed CPA solution while collecting volume measurements using a Coulter Counter. These experiments were performed at temperatures ranging from 4 to 37 °C for exposure to dimethyl sulfoxide, glycerol, ethylene glycol and propylene glycol. The best-fit water permeability was similar in the presence of all of the CPAs, with an average value at 21 °C of 0.18 μm atm−1 min−1. The activation energy for water transport ranged from 41 to 61 kJ/mol. The CPA permeability at 21 °C was 6.4, 1.0, 8.4 and 4.0 μm/min for dimethyl sulfoxide, glycerol, ethylene glycol and propylene glycol, respectively, and the activation energy for CPA transport ranged between 59 and 68 kJ/mol. PMID:24269528

  14. A sulfonium cation intermediate in the mechanism of methionine sulfoxide reductase B: a DFT study.

    PubMed

    Robinet, Jesse J; Dokainish, Hisham M; Paterson, David J; Gauld, James W

    2011-07-28

    The hybrid density functional theory method B3LYP in combination with three systematically larger active site models has been used to investigate the substrate binding and catalytic mechanism by which Neisseria gonorrhoeae methionine sulfoxide reductase B (MsrB) reduces methionine-R-sulfoxide (Met-R-SO) to methionine. The first step in the overall mechanism is nucleophilic attack of an active site thiolate at the sulfur of Met-R-SO to form an enzyme-substrate sulfurane. This occurs with concomitant proton transfer from an active site histidine (His480) residue to the substrates oxygen center. The barrier for this step, calculated using our largest most complete active site model, is 17.2 kJ mol(-1). A subsequent conformational rearrangement and intramolecular -OH transfer to form an enzyme-derived sulfenic acid ((Cys495)S-OH) is not enzymatically feasible. Instead, transfer of a second proton from a second histidyl active site residue (His477) to the sulfurane's oxygen center to give water and a sulfonium cation intermediate is found to be greatly preferred, occurring with a quite low barrier of just 1.2 kJ mol(-1). Formation of the final product complex in which an intraprotein disulfide bond is formed with generation of methionine preferably occurs in one step via nucleophilic attack of the sulfur of a second enzyme thiolate ((Cys440)S(-)) at the S(Cys495) center of the sulfonium intermediate with a barrier of 23.8 kJ mol(-1). An alternate pathway for formation of the products via a sulfenic acid intermediate involves enzymatically feasible, but higher energy barriers. The role and impact of hydrogen bonding and active site residues on the properties and stability of substrate and mechanism intermediates and the affects of mutating His477 are also examined and discussed. PMID:21721538

  15. Membrane permeability of the human granulocyte to water, dimethyl sulfoxide, glycerol, propylene glycol and ethylene glycol.

    PubMed

    Vian, Alex M; Higgins, Adam Z

    2014-02-01

    Granulocytes are currently transfused as soon as possible after collection because they rapidly deteriorate after being removed from the body. This short shelf life complicates the logistics of granulocyte collection, banking, and safety testing. Cryopreservation has the potential to significantly increase shelf life; however, cryopreservation of granulocytes has proven to be difficult. In this study, we investigate the membrane permeability properties of human granulocytes, with the ultimate goal of using membrane transport modeling to facilitate development of improved cryopreservation methods. We first measured the equilibrium volume of human granulocytes in a range of hypo- and hypertonic solutions and fit the resulting data using a Boyle-van't Hoff model. This yielded an isotonic cell volume of 378 μm(3) and an osmotically inactive volume of 165 μm(3). To determine the permeability of the granulocyte membrane to water and cryoprotectant (CPA), cells were injected into well-mixed CPA solution while collecting volume measurements using a Coulter Counter. These experiments were performed at temperatures ranging from 4 to 37°C for exposure to dimethyl sulfoxide, glycerol, ethylene glycol, and propylene glycol. The best-fit water permeability was similar in the presence of all of the CPAs, with an average value at 21°C of 0.18 μmatm(-1)min(-1). The activation energy for water transport ranged from 41 to 61 kJ/mol. The CPA permeability at 21°C was 6.4, 1.0, 8.4, and 4.0 μm/min for dimethyl sulfoxide, glycerol, ethylene glycol, and propylene glycol, respectively, and the activation energy for CPA transport ranged between 59 and 68 kJ/mol. PMID:24269528

  16. Ischemic Acute Kidney Injury Perturbs Homeostasis of Serine Enantiomers in the Body Fluid in Mice: Early Detection of Renal Dysfunction Using the Ratio of Serine Enantiomers

    PubMed Central

    Sasabe, Jumpei; Suzuki, Masataka; Miyoshi, Yurika; Tojo, Yosuke; Okamura, Chieko; Ito, Sonomi; Konno, Ryuichi; Mita, Masashi; Hamase, Kenji; Aiso, Sadakazu

    2014-01-01

    The imbalance of blood and urine amino acids in renal failure has been studied mostly without chiral separation. Although a few reports have shown the presence of D-serine, an enantiomer of L-serine, in the serum of patients with severe renal failure, it has remained uncertain how serine enantiomers are deranged in the development of renal failure. In the present study, we have monitored serine enantiomers using a two-dimensional HPLC system in the serum and urine of mice after renal ischemia-reperfusion injury (IRI), known as a mouse model of acute kidney injury. In the serum, the level of D-serine gradually increased after renal IRI in parallel with that of creatinine, whereas the L-serine level decreased sharply in the early phase after IRI. The increase of D-serine was suppressed in part by genetic inactivation of a D-serine-degrading enzyme, D-amino acid oxidase (DAO), but not by disruption of its synthetic enzyme, serine racemase, in mice. Renal DAO activity was detected exclusively in proximal tubules, and IRI reduced the number of DAO-positive tubules. On the other hand, in the urine, D-serine was excreted at a rate nearly triple that of L-serine in mice with sham operations, indicating that little D-serine was reabsorbed while most L-serine was reabsorbed in physiological conditions. IRI significantly reduced the ratio of urinary D−/L-serine from 2.82±0.18 to 1.10±0.26 in the early phase and kept the ratio lower than 0.5 thereafter. The urinary D−/L-serine ratio can detect renal ischemia earlier than kidney injury molecule-1 (KIM-1) or neutrophil gelatinase-associated lipocalin (NGAL) in the urine, and more sensitively than creatinine, cystatin C, or the ratio of D−/L-serine in the serum. Our findings provide a novel understanding of the imbalance of amino acids in renal failure and offer a potential new biomarker for an early detection of acute kidney injury. PMID:24489731

  17. Enantioseparation and determination of triticonazole enantiomers in fruits, vegetables, and soil using efficient extraction and clean-up methods.

    PubMed

    Zhang, Qing; Gao, Beibei; Tian, Mingming; Shi, Haiyan; Hua, Xiude; Wang, Minghua

    2016-01-15

    An efficient and novel enantioseparation and determination method was developed to quantify the enantiomers of chiral triazole fungicide triticonazole in fruit, vegetable, and soil samples. Under the optimal chromatographic conditions, the enantiomers of triticonazole were completely enantioseparated on a cellulose tris(3-chloro-4-methyl phenyl carbamate) column with relatively good resolution (Rs=14.04). Two cleanup methods were compared to quantify the enantiomers of triticonazole. The modified QuEChERS (quick, easy, cheap, effective, rugged and safe) extraction procedure was achieved with sufficient recoveries and low detection limits. Good recoveries were obtained for the two enantiomers ranging from 84.1% to 103.2% in the six matrices, and the relative standard deviation values ranged from 1.7% to 8.4%. Under the optimal conditions, the obtained limits of detection (LODs) were in the range of 0.0012-0.0031mg/kg for the two enantiomers, and the limits of quantification (LOQs) were in the range of 0.0036-0.0091mg/kg, which were lower than the maximum residue levels established in Japan. In addition, the stereochemical structure of triticonazole enantiomers were determined for the first time using a combination of experimental and predicted electronic circular dichroism (ECD) spectra. The first eluted enantiomer was confirmed to be (+)-(S)-triticonazole. These results indicate that the proposed method is convenient and reliable for the enantioselective detection of triticonazole in authentic samples. The proposed method could be widely applicable for investigating the stereoselective degradation of triticonazole in food and environmental matrices, providing additional information for reliable risk assessment of triazole fungicides. PMID:26724558

  18. Population deworming every 6 months with albendazole in 1 million pre-school children in north India: DEVTA, a cluster-randomised trial

    PubMed Central

    Awasthi, Shally; Peto, Richard; Read, Simon; Richards, Susan M; Pande, Vinod; Bundy, Donald; the DEVTA (Deworming and Enhanced Vitamin A) team

    2013-01-01

    Summary Background In north India many pre-school children are underweight, many have intestinal worms, and 2–3% die at ages 1·0–6·0 years. We used the state-wide Integrated Child Development Service (ICDS) infrastructure to help to assess any effects of regular deworming on mortality. Methods Participants in this cluster-randomised study were children in catchment areas of 8338 ICDS-staffed village child-care centres (under-5 population 1 million) in 72 administrative blocks. Groups of four neighbouring blocks were cluster-randomly allocated in Oxford between 6-monthly vitamin A (retinol capsule of 200 000 IU retinyl acetate in oil, to be cut and dripped into the child's mouth every 6 months), albendazole (400 mg tablet every 6 months), both, or neither (open control). Analyses of albendazole effects are by block (36 vs 36 clusters). The study spanned 5 calendar years, with 11 6-monthly mass-treatment days for all children then aged 6–72 months. Annually, one centre per block was randomly selected and visited by a study team 1–5 months after any trial deworming to sample faeces (for presence of worm eggs, reliably assessed only after mid-study), weigh children, and interview caregivers. Separately, all 8338 centres were visited every 6 months to monitor pre-school deaths (100 000 visits, 25 000 deaths at age 1·0–6·0 years [the primary outcome]). This trial is registered at ClinicalTrials.gov, NCT00222547. Findings Estimated compliance with 6-monthly albendazole was 86%. Among 2589 versus 2576 children surveyed during the second half of the study, nematode egg prevalence was 16% versus 36%, and most infection was light. After at least 2 years of treatment, weight at ages 3·0–6·0 years (standardised to age 4·0 years, 50% male) was 12·72 kg albendazole versus 12·68 kg control (difference 0·04 kg, 95% CI −0·14 to 0·21, p=0·66). Comparing the 36 albendazole-allocated versus 36 control blocks in analyses of the primary outcome, deaths

  19. Decline in lymphatic filariasis transmission with annual mass drug administration using DEC with and without albendazole over a 10year period in India.

    PubMed

    Sunish, I P; Kalimuthu, M; Rajendran, R; Munirathinam, A; Ashok Kumar, V; Nagaraj, J; Tyagi, B K

    2015-02-01

    The National Programme for the Elimination of Lymphatic Filariasis is underway in the endemic districts of Tamil Nadu State, South India, since 2001. Annual mass drug administration (MDA) was carried out by the state health department to all eligible individuals. The impact of MDAs on transmission parameters was evaluated in 2 revenue blocks, viz, one with DEC alone and the other with a combination of albendazole. After 10 years with 6 annual MDAs, the transmission indices reached low levels in both treatment arms, but still persisted. However, the DEC alone arm showed higher transmission rates, compared to the DEC+ALB arm. Few villages which demonstrated persistent transmission need to be targeted with an additional control measure viz, vector control, to achieve LF elimination. It is evident from the 10 year period of the study that inclusion of albendazole along with DEC has significantly reduced the transmission indices to almost nil level, as compared to DEC alone.

  20. Stereoselective recognition of the enantiomers of phenglutarimide and of six related compounds by four muscarinic receptor subtypes.

    PubMed Central

    Waelbroeck, M.; Lazareno, S.; Pfaff, O.; Friebe, T.; Tastenoy, M.; Mutschler, E.; Lambrecht, G.

    1996-01-01

    1. We have compared the binding properties of the enantiomers of phenglutarimide (1) and of six related compounds to M1 receptors in NB-OK-1 cells, M2 receptors in rat heart, M3 receptors in rat pancreas and the M4 receptors of rat striatum, with their functional (antimuscarinic) properties in rabbit vas deferens (M1/M4-like), guinea-pig atria (M2) and guinea-pig ileum (M3) receptors. The binding properties of the enantiomers of three of the compounds were also measured on cloned human m1-m4 receptors expressed by CHO cells, using [3H]-N-methylscopolamine ([3H]-NMS) as radioligand. 2. The high affinity enantiomers behaved as competitive antagonists in binding and pharmacological studies. (S)-phenglutarimide (pKi-M1 = 9.0/9.3) and (R)-thienglutarimide (pKi-M1 = 8.6/9.2) recognized selectively the native M1 > M4 > M3 > M2 receptors in tissues as well as the respective cloned receptors. 3. The pA2 values at the inhibitory heteroreceptors in the rabbit vas deferens, and at the guinea-pig atria and ileum for the seven more potent enantiomers were compatible with the previous classification of these receptors as M1/M4-like, M2 and M3, respectively. 4. Replacement of the phenyl by a thienyl ring or of the diethylamino by a piperidino group in the phenglutarimide molecule did not affect markedly the potencies of the high affinity enantiomer. In contrast, replacement of the phenyl by a cyclohexyl ring decreased 20 fold the active enantiomers potency. Methylation of the piperidine-2,6-dione nitrogen also reduced markedly the eutomers' affinities, more on the M1 than on the other subtypes. 5. The selectivity profiles (recognition of four receptor subtypes) of six of the seven less active enantiomers were different from the corresponding more active enantiomers selectivity profiles, suggesting that the preparations used in this study were pure. However, we cannot not exclude the hypothesis that the batch of (S)-thienglutarimide used in this study was contaminated by less than

  1. A randomized controlled trial of increased dose and frequency of albendazole with standard dose DEC for treatment of Wuchereria bancrofti microfilaremics in Odisha, India.

    PubMed

    Kar, Shantanu Kumar; Dwibedi, Bhagirathi; Kerketa, Anna Salomi; Maharana, Antaryami; Panda, Sudanshu S; Mohanty, Prafulla Chandra; Horton, John; Ramachandran, Cherubala P

    2015-03-01

    Although current programmes to eliminate lymphatic filariasis have made significant progress it may be necessary to use different approaches to achieve the global goal, especially where compliance has been poor and 'hot spots' of continued infection exist. In the absence of alternative drugs, the use of higher or more frequent dosing with the existing drugs needs to be explored. We examined the effect of higher and/or more frequent dosing with albendazole with a fixed 300 mg dose of diethylcarbamazine in a Wuchereria bancrofti endemic area in Odisha, India. Following screening, 104 consenting adults were randomly assigned to treatment with the standard regimen annually for 24 months (S1), or annually with increased dose (800 mg albendazole)(H1) or with increased frequency (6 monthly) with either standard (S2) or increased (H2) dose. Pre-treatment microfilaria counts (GM) ranged from 348 to 459 mf/ml. Subjects were followed using microfilaria counts, OG4C3 antigen levels and ultrasound scanning for adult worm nests. Microfilarial counts tended to decrease more rapidly with higher or more frequent dosing at all time points. At 12 months, Mf clearance was marginally greater with the high dose regimens, while by 24 months, there was a trend to higher Mf clearance in the arm with increased frequency and 800 mg of albendazole (76.9%) compared to other arms, (S1:64%, S2:69.2% & H1:73.1%). Although higher and/or more frequent dosing showed a trend towards a greater decline in antigenemia and clearance of "nests", all regimens demonstrated the potential macrofilaricidal effect of the combination. The higher doses of albendazole did not result in a greater number or more severe side effects. The alternative regimens could be useful in the later stages of existing elimination programmes or achieving elimination more rapidly in areas where programmes have yet to start. PMID:25781977

  2. Effect of single-dose albendazole and vitamin A supplementation on the iron status of pre-school children in Sichuan, China.

    PubMed

    Chen, Ke; Xie, Hu Mina; Tian, Weizheng; Zheng, Xiaoling; Jiang, Alice C

    2016-04-01

    The aim of this study was to explore the effect of single-dose albendazole and vitamin A intervention on the anaemic status and Fe metabolism of pre-school children. This study was a randomised, placebo-controlled and double-blinded intervention trial. All eligible anaemic pre-school children were randomly divided into three groups: group 1 received no intervention, which served as the control group, group 2 received 400 mg single-dose albendazole administration and group 3 received a 60000 μg vitamin A capsule combined with 400 mg single-dose albendazole at the beginning of the study. The follow-up period was for 6 months. Anthropometry and biochemical index about Fe metabolism were measured before and after intervention. A total of 209 pre-school anaemic children were randomly divided into three intervention groups (sixty-four, sixty-two and sixty for groups 1, 2 and 3, respectively). The mean age of the children in the study was 4·4 (sd 0·7) years and 50·5 % of the children were female (94/186). After a follow-up period of 6 months, the levels of serum retinol, ferritin, transferrin receptor-ferritin index and body total Fe content of children in group 3 were significantly higher compared with children in groups 1 and 2 (P<0·05). Moreover, the proportion of vitamin A deficiency, marginal vitamin A deficiency and Fe deficiency among children in group 3 were markedly lower compared with children in groups 1 and 2 (P<0·05). Albendazole plus vitamin A administration showed more efficacy on the improvement of serum retinol and Fe metabolic status.

  3. A Randomized Controlled Trial of Increased Dose and Frequency of Albendazole with Standard Dose DEC for Treatment of Wuchereria bancrofti Microfilaremics in Odisha, India

    PubMed Central

    Kerketa, Anna Salomi; Maharana, Antaryami; Panda, Sudanshu S; Mohanty, Prafulla Chandra; Horton, John; Ramachandran, Cherubala P

    2015-01-01

    Although current programmes to eliminate lymphatic filariasis have made significant progress it may be necessary to use different approaches to achieve the global goal, especially where compliance has been poor and ‘hot spots’ of continued infection exist. In the absence of alternative drugs, the use of higher or more frequent dosing with the existing drugs needs to be explored. We examined the effect of higher and/or more frequent dosing with albendazole with a fixed 300mg dose of diethylcarbamazine in a Wuchereria bancrofti endemic area in Odisha, India. Following screening, 104 consenting adults were randomly assigned to treatment with the standard regimen annually for 24 months (S1), or annually with increased dose (800mg albendazole)(H1) or with increased frequency (6 monthly) with either standard (S2) or increased (H2) dose. Pre-treatment microfilaria counts (GM) ranged from 348 to 459 mf/ml. Subjects were followed using microfilaria counts, OG4C3 antigen levels and ultrasound scanning for adult worm nests. Microfilarial counts tended to decrease more rapidly with higher or more frequent dosing at all time points. At 12 months, Mf clearance was marginally greater with the high dose regimens, while by 24 months, there was a trend to higher Mf clearance in the arm with increased frequency and 800mg of albendazole (76.9%) compared to other arms, (S1:64%, S2:69.2% & H1:73.1%). Although higher and/or more frequent dosing showed a trend towards a greater decline in antigenemia and clearance of “nests”, all regimens demonstrated the potential macrofilaricidal effect of the combination. The higher doses of albendazole did not result in a greater number or more severe side effects. The alternative regimens could be useful in the later stages of existing elimination programmes or achieving elimination more rapidly in areas where programmes have yet to start. PMID:25781977

  4. Using dispersive liquid-liquid microextraction and liquid chromatography for determination of guaifenesin enantiomers in human urine.

    PubMed

    Hatami, Mehdi; Farhadi, Khalil; Abdollahpour, Assem

    2011-11-01

    A simple, rapid, and efficient method, dispersive liquid-liquid microextraction (DLLME) coupled with high-performance liquid chromatography-fluorescence detector, has been developed for the determination of guaifenesin (GUA) enantiomers in human urine samples after an oral dose administration of its syrup formulation. Urine samples were collected during the time intervals 0-2, 2-4, and 4-6 h and concentration and ratio of two enantiomers was determined. The ratio of R-(-) to S-(+) enantiomer concentrations in urine showed an increase with time, with R/S ratios of 0.66 at 2 h and 2.23 at 6 h. For microextraction process, a mixture of extraction solvent (dichloromethane, 100 μL) and dispersive solvent (THF, 1 mL) was rapidly injected into 5.0 mL diluted urine sample for the formation of cloudy solution and extraction of enantiomers into the fine droplets of CH(2)Cl(2). After optimization of HPLC enantioselective conditions, some important parameters, such as the kind and volume of extraction and dispersive solvents, extraction time, temperature, pH, and salt effect were optimized for dispersive liquid-liquid microextraction process. Under the optimum extraction condition, the method yields a linear calibration curve in the concentration range from 10 to 2000 ng/mL for target analytes. LOD was 3.00 ng/mL for both of the enantiomers. PMID:21972192

  5. Separation of tryptophan-derivative enantiomers with iron-free human serum transferrin by capillary zone electrophoresis.

    PubMed

    Kilár, F; Fanali, S

    1995-08-01

    Enantiomers can be separated by using human serum transferrin as a chiral phase. With the help of the native protein we were able to separate enantiomers with high efficiency, using a low ionic strength 2-(N-morpholino)ethanesulfonic acid (MES) buffer, pH 6, in capillary zone electrophoresis. Tryptophan methyl, ethyl and butyl ester enantiomers-moving towards the cathode at pH 6-were resolved by passing through an iron-free transferrin zone in coated capillaries. Since the isoelectric point of the iron-free transferrin is a little higher than 6, the protein zone is either not moving in the experiment or is slowly moving towards the anode. Under the simplest experimental conditions the highest resolution was obtained for the butyl ester enantiomers and the lowest for the methyl ester ones. By changing the experimental conditions, however, this order could be reversed. The results indicate that the lengths of the alkyl chains in the enantiomers have a significant effect on the resolution, i.e., on the interaction between the protein and the separands.

  6. Determination of bevantolol enantiomers in human plasma by coupled achiral-chiral high performance-liquid chromatography.

    PubMed

    Oh, Joung Weon; Trung, Tran Quoc; Sin, Kwan Seog; Kang, Jong Seong; Kim, Kyeong Ho

    2007-07-01

    A coupled achiral-chiral high performance liquid chromatographic method was developed and fully validated for the determination of bevantolol enantiomers, (-)-(S)-bevantolol and (+)-(R)-bevantolol, in human plasma. Plasma samples were prepared by solid phase extraction with Sep-Pak Plus C18 cartridges followed by HPLC. Bevantolol enantiomers and (+)-(R)-Propranolol as internal standard (IS) were preseparated from interfering components in plasma on a Phenomenex silica column and bevantolol enantiomers and IS were resolved and determined on a Chiralcel OJ-H chiral stationary phase. The two columns were connected by a switching valve equipped with silica precolumn. The Precolumn was used to concentrate bevantolol in the eluent from the achiral column before back flushing onto chiral phase. A detailed validation of the method was performed accordingly to FDA guidelines. For each enantiomer the assay was linear between 20 and 1600 ng/ml. The quantification limits of both bevantolol enantiomers were 20 ng/ml. The intraday variation was between 1.07 and 12.64% in relation to the measured concentration and the interday variation was 0.91 and 11.79%. The method has been applied to the determination of (-)-(S)- and (+)-(R)-bevantolol in plasma from healthy volunteers dosed with racemic bevantolol hydrochloride.

  7. Impact of molecular flexibility on double polymorphism, solid solutions and chiral discrimination during crystallization of diprophylline enantiomers.

    PubMed

    Brandel, Clément; Amharar, Youness; Rollinger, Judith M; Griesser, Ulrich J; Cartigny, Yohann; Petit, Samuel; Coquerel, Gérard

    2013-10-01

    The polymorphic behavior of racemic and enantiopure diprophylline (DPL), a chiral derivative of theophylline marketed as a racemic solid, has been investigated by combining differential scanning calorimetry, powder X-ray diffraction, hot-stage microscopy and single-crystal X-ray experiments. The pure enantiomers were obtained by a chemical synthesis route, and additionally an enantioselective crystallization procedure was developed. The binary phase diagram between the DPL enantiomers was constructed and revealed a double polymorphism (i.e., polymorphism both of the racemic mixture and of the pure enantiomer). The study of the various equilibria in this highly unusual phase diagram revealed a complex situation since mixtures of DPL enantiomers can crystallize either as a stable racemic compound, a metastable conglomerate, or two distinct metastable solid solutions. Crystal structure analysis revealed that the DPL molecules adopt different conformations in the crystal forms suggesting that the conformational degrees of freedom of the substituent that carries the only two H-bond donor groups might be related to the versatile crystallization behavior of DPL. The control of these equilibria and the use of a suitable solvent allowed the design of an efficient protocol for the preparative resolution of racemic DPL via preferential crystallization. Therefore, the resolution of DPL enantiomers despite the existence of a racemic compound stable at any temperature demonstrates that the detection of a stable conglomerate is not mandatory for the implementation of preferential crystallization.

  8. Enantiomer Profiling of Methamphetamine in White Crystal and Tablet Forms (Ma Old) Using LC-MS-MS.

    PubMed

    Wang, Ting; Yu, Zhiguo; Shi, Yan; Xiang, Ping

    2015-09-01

    At the global level, seizures of crystalline methamphetamine (MA) and MA tablets have risen to a new high, indicating that the substance is an imminent threat. MA enantiomer profiling was a useful tool to investigate the prevalence of MA abuse, the intrinsic characteristics of the seized samples and the trends of precursors. In this work, the distribution of enantiomers in clandestine MA crystals and tablets seized mainly in the Yangtze River Delta region, China, from 2008 to 2014 were identified. The MA samples were diluted with internal standard methanol solution, and analyzed by LC-MS-MS. The detection limits of the enantiomers were 0.04 μg/L. The limit of quantification was 0.1 μg/L. As little as 0.2% of the R-enantiomer ratio could be determined. Standard calibration curves of S- and R-MA showed good linearity in the range of 0.1-80 μg/L (r(2) > 0.995). All of the seizures were optically pure S-enantiomer in the years 2008 and 2009. Seized samples containing a slight amount of R-MA began to appear in 2010 and increased in the year 2014. No racemic mixture or R-isomer of MA was seized. From this study, we could find out that smuggling routes and/or precursors might be silently changing in the Yangtze River Delta region, China.

  9. The two enantiomers of tetrahydropalmatine are inhibitors of P-gp, but not inhibitors of MRP1 or BCRP.

    PubMed

    Sun, Siyuan; Chen, Zhongjian; Li, Liping; Sun, Dongli; Tian, Ye; Pan, Hao; Bi, Huichang; Huang, Min; Zeng, Su; Jiang, Huidi

    2012-12-01

    Tetrahydropalmatine (THP), with one chiral centre, is one of the major constituents of Rhizoma corydalis. THP is considered to possess analgesic, sedative, hypnotic actions and cardiac protection. The aim of this study was to elucidate the stereoselective interaction between THP and ABC transporters. The present study investigated three most important ABC transporters, including P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1) and breast cancer resistance protein (BCRP). The intracellular accumulation and bidirectional transport suggested THP enantiomers were inhibitors of P-gp, but not of MRP1 or BCRP. The IC(50) values of (-)-THP and (+)-THP on rhodamine 123 (P-gp substrate) efflux were 48.6 and 20.0 µM, respectively, which showed obvious stereoselective difference. In the bidirectional transport, THP enantiomers showed high passive permeability and the contribution of P-gp could not be testified. The western blot and real-time RT-PCR assays showed that THP enantiomers reduced the protein expression of P-gp, but did not affect its mRNA expression. In in vitro cytotoxicity test, THP enantiomers showed the potential of increasing the cytotoxicity of doxorubicin in P-gp-mediated multidrug resistant tumour cells. The present study showed the stereoselective interaction between THP enantiomers and P-gp, which should be considered in clinical practice. PMID:22900779

  10. Application of a cDNA microarray for profiling the gene expression of Echinococcus granulosus protoscoleces treated with albendazole and artemisinin.

    PubMed

    Lü, Guodong; Zhang, Wenbao; Wang, Jianhua; Xiao, Yunfeng; Zhao, Jun; Zhao, Jianqin; Sun, Yimin; Zhang, Chuanshan; Wang, Junhua; Lin, Renyong; Liu, Hui; Zhang, Fuchun; Wen, Hao

    2014-12-01

    Cystic echinoccocosis (CE) is a neglected zoonosis that is caused by the dog-tapeworm Echinococcus granulosus. The disease is endemic worldwide. There is an urgent need for searching effective drug for the treatment of the disease. In this study, we sequenced a cDNA library constructed using RNA isolated from oncospheres, protoscoleces, cyst membrane and adult worms of E. granulosus. A total of 9065 non-redundant or unique sequences were obtained and spotted on chips as uniEST probes to profile the gene expression in protoscoleces of E. granulosus treated with the anthelmintic drugs albendazole and artemisinin, respectively. The results showed that 7 genes were up-regulated and 38 genes were down-regulated in the protoscoleces treated with albendazole. Gene analysis showed that these genes are responsible for energy metabolism, cell cycle and assembly of cell structure. We also identified 100 genes up-regulated and 6 genes down-regulated in the protoscoleces treated with artemisinin. These genes play roles in the transduction of environmental signals, and metabolism. Albendazole appeared its drug efficacy in damaging cell structure, while artemisinin was observed to increase the formation of the heterochromatin in protoscolex cells. Our results highlight the utility of using cDNA microarray methods to detect gene expression profiles of E. granulosus and, in particular, to understand the pharmacologic mechanism of anti-echinococcosis drugs.

  11. Characterization of Albendazole-Randomly Methylated-β-Cyclodextrin Inclusion Complex and In Vivo Evaluation of Its Antihelmitic Activity in a Murine Model of Trichinellosis

    PubMed Central

    García, Agustina; Leonardi, Darío; Vasconi, María D.; Hinrichsen, Lucila I.; Lamas, María C.

    2014-01-01

    Albendazole is a benzimidazole carbamate extensively used in oral chemotherapy against intestinal parasites, due to its broad spectrum activity, good tolerance and low cost. However, the drug has the disadvantage of poor bioavailability due to its very low solubility in water; as a consequence, a very active area of research focuses on the development of new pharmaceutical formulations to increase its solubility, dissolution rate, and bioavailability. The primary objective of this study was to prepare randomly methylated β-cyclodextrins inclusion complexes to increase albendazole dissolution rate, in order to enhance its antiparasitic activity. This formulation therapeutic efficacy was contrasted with that of the pure drug by treating Trichinella spiralis infected mice during the intestinal phase of the parasite cycle, on days five and six post-infection. This protocol significantly decreased muscle larval burden measured in the parenteral stage on day 30 post-infection, when compared with the untreated control. Thus, it could be demonstrated that the inclusion complexes improve the in vivo therapeutic activity of albendazole. PMID:25406084

  12. Preparative separation of enantiomers based on functional nucleic acids modified gold nanoparticles.

    PubMed

    Huang, Rong; Wang, Daifang; Liu, Shuzhen; Guo, Longhua; Wang, Fangfang; Lin, Zhenyu; Qiu, Bin; Chen, Guonan

    2013-11-01

    The preparative-scale separation of chiral compounds is vitally important for the pharmaceutical industry and related fields. Herein we report a simple approach for rapid preparative separation of enantiomers using functional nucleic acids modified gold nanoparticles (AuNPs). The separation of DL-tryptophan (DL-Trp) is demonstrated as an example to show the feasibility of the approach. AuNPs modified with enantioselective aptamers were added into a racemic mixture of DL -Trp. The aptamer-specific enantiomer (L-Trp) binds to the AuNPs surface through aptamer-L-Trp interaction. The separation of DL-Trp is then simply accomplished by centrifugation: the precipitate containing L-Trp bounded AuNPs is separated from the solution, while the D-Trp remains in the supernatant. The precipitate is then redispersed in water. The aptamer is denatured under 95 °C and a second centrifugation is then performed, resulting in the separation of AuNPs and L-Trp. The supernatant is finally collected to obtain pure L-Trp in water. The results show that the racemic mixture of DL-Trp is completely separated into D-Trp and L-Trp, respectively, after 5 rounds of repeated addition of fresh aptamer-modified AuNPs to the DL-Trp mixture solution. Additionally, the aptamer-modified AuNPs can be repeatedly used for at least eight times without significant loss of its binding ability because the aptamer can be easily denatured and renatured in relatively mild conditions. The proposed approach could be scaled up and extended to the separation of other enantiomers by the adoption of other enantioselective aptamers.

  13. Scalable Preparation and Differential Pharmacologic and Toxicologic Profiles of Primaquine Enantiomers

    PubMed Central

    Tekwani, Babu L.; Herath, H. M. T. Bandara; Sahu, Rajnish; Gettayacamin, Montip; Tungtaeng, Anchalee; van Gessel, Yvonne; Baresel, Paul; Wickham, Kristina S.; Bartlett, Marilyn S.; Fronczek, Frank R.; Melendez, Victor; Ohrt, Colin; Reichard, Gregory A.; McChesney, James D.; Rochford, Rosemary; Walker, Larry A.

    2014-01-01

    Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) activity is the major limitation of primaquine (PQ), the only antimalarial drug in clinical use for treatment of relapsing Plasmodium vivax malaria. PQ is currently clinically used in its racemic form. A scalable procedure was developed to resolve racemic PQ, thus providing pure enantiomers for the first time for detailed preclinical evaluation and potentially for clinical use. These enantiomers were compared for antiparasitic activity using several mouse models and also for general and hematological toxicities in mice and dogs. (+)-(S)-PQ showed better suppressive and causal prophylactic activity than (−)-(R)-PQ in mice infected with Plasmodium berghei. Similarly, (+)-(S)-PQ was a more potent suppressive agent than (−)-(R)-PQ in a mouse model of Pneumocystis carinii pneumonia. However, at higher doses, (+)-(S)-PQ also showed more systemic toxicity for mice. In beagle dogs, (+)-(S)-PQ caused more methemoglobinemia and was toxic at 5 mg/kg of body weight/day given orally for 3 days, while (−)-(R)-PQ was well tolerated. In a novel mouse model of hemolytic anemia associated with human G6PD deficiency, it was also demonstrated that (−)-(R)-PQ was less hemolytic than (+)-(S)-PQ for the G6PD-deficient human red cells engrafted in the NOD-SCID mice. All these data suggest that while (+)-(S)-PQ shows greater potency in terms of antiparasitic efficacy in rodents, it is also more hematotoxic than (−)-(R)-PQ in mice and dogs. Activity and toxicity differences of PQ enantiomers in different species can be attributed to their different pharmacokinetic and metabolic profiles. Taken together, these studies suggest that (−)-(R)-PQ may have a better safety margin than the racemate in human. PMID:24913163

  14. Enantiomers of 3-methylspermidine selectively modulate deoxyhypusine synthesis and reveal important determinants for spermidine transport.

    PubMed

    Hyvönen, Mervi T; Khomutov, Maxim; Petit, Marine; Weisell, Janne; Kochetkov, Sergey N; Alhonen, Leena; Vepsäläinen, Jouko; Khomutov, Alex R; Keinänen, Tuomo A

    2015-06-19

    Eukaryotic translation initiation factor 5A (eIF5A) is essential for cell proliferation, becoming functionally active only after post-translational conversion of a specific Lys to hypusine [N(ε)-(4-amino-2-hydroxybutyl)lysine]. Deoxyhypusine synthase (DHS) is the rate-limiting enzyme of this two-step process, and the polyamine spermidine is the only natural donor of the butylamine group for this reaction, which is very conserved-hypusine biosynthesis suffers last when the intracellular spermidine pool is depleted. DHS has a very strict substrate specificity, and only a few spermidine analogs are substrates of the enzyme and can support long-term growth of spermidine-depleted cells. Herein, we compared the biological properties of earlier unknown enantiomers of 3-methylspermidine (3-MeSpd) in deoxyhypusine synthesis, in supporting cell growth and in polyamine transport. Long-term treatment of DU145 cells with α-difluoromethylornithine (inhibitor of polyamine biosynthesis) and (R)-3-MeSpd did not cause depletion of hypusinated eIF5A, and the cells were still able to grow, whereas the combination of α-difluoromethylornithine with a racemate or (S)-3-MeSpd caused cessation of cell growth. Noticeably, DHS preferred the (R)- over the (S)-enantiomer as a substrate. (R)-3-MeSpd competed with [(14)C]-labeled spermidine for cellular uptake less efficiently than the (S)-3-MeSpd (Ki = 141 μM vs 19 μM, respectively). The cells treated with racemic 3-MeSpd accumulated intracellularly mainly (S)-3-MeSpd, but not DHS substrate (R)-3-MeSpd, explaining the inability of the racemate to support long-term growth. The distinct properties of 3-MeSpd enantiomers can be exploited in designing polyamine uptake inhibitors, facilitating drug delivery and modulating deoxyhypusine synthesis.

  15. Biological activity of the enantiomers of 3-methylhentriacontane, a queen pheromone of the ant Lasius niger.

    PubMed

    Motais de Narbonne, Marine; van Zweden, Jelle S; Bello, Jan E; Wenseleers, Tom; Millar, Jocelyn G; d'Ettorre, Patrizia

    2016-06-01

    Queen pheromones are essential for regulation of the reproductive division of labor in eusocial insect species. Although only the queen is able to lay fertilized eggs and produce females, in some cases workers may develop their ovaries and lay male-destined eggs, thus reducing the overall colony efficiency. As long as the queen is healthy, it is usually in the workers' collective interest to work for the colony and remain sterile. Queens signal their fertility via pheromones, which may have a primer effect, affecting the physiology of workers, or a releaser effect, influencing worker behavior. The queen pheromone of the ant Lasius niger was among the first queen pheromones of social insects to be identified. Its major component is 3-methylhentriacontane (3-MeC31), which is present in relatively large amounts on the queen's cuticle and on her eggs. 3-MeC31 regulates worker reproduction by inhibiting ovarian development. Most monomethyl-branched hydrocarbons can exist in two stereoisomeric forms. The correct stereochemistry is fundamental to the activity of most bioactive molecules, but this has rarely been investigated for methyl-branched hydrocarbons. Here, we tested the bioactivity of the (S)- and (R)-enantiomers of 3-MeC31, and found that whereas both enantiomers were effective in suppressing worker ovarian development, (S)-3-MeC31 appeared to be more effective at suppressing aggressive behavior by workers. This suggests that the natural pheromone may be a mixture of the two enantiomers. The enantiomeric ratio produced by queens remains unknown because of the small amounts of the compound available from each queen. PMID:26994182

  16. Scalable preparation and differential pharmacologic and toxicologic profiles of primaquine enantiomers.

    PubMed

    Nanayakkara, N P Dhammika; Tekwani, Babu L; Herath, H M T Bandara; Sahu, Rajnish; Gettayacamin, Montip; Tungtaeng, Anchalee; van Gessel, Yvonne; Baresel, Paul; Wickham, Kristina S; Bartlett, Marilyn S; Fronczek, Frank R; Melendez, Victor; Ohrt, Colin; Reichard, Gregory A; McChesney, James D; Rochford, Rosemary; Walker, Larry A

    2014-08-01

    Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) activity is the major limitation of primaquine (PQ), the only antimalarial drug in clinical use for treatment of relapsing Plasmodium vivax malaria. PQ is currently clinically used in its racemic form. A scalable procedure was developed to resolve racemic PQ, thus providing pure enantiomers for the first time for detailed preclinical evaluation and potentially for clinical use. These enantiomers were compared for antiparasitic activity using several mouse models and also for general and hematological toxicities in mice and dogs. (+)-(S)-PQ showed better suppressive and causal prophylactic activity than (-)-(R)-PQ in mice infected with Plasmodium berghei. Similarly, (+)-(S)-PQ was a more potent suppressive agent than (-)-(R)-PQ in a mouse model of Pneumocystis carinii pneumonia. However, at higher doses, (+)-(S)-PQ also showed more systemic toxicity for mice. In beagle dogs, (+)-(S)-PQ caused more methemoglobinemia and was toxic at 5 mg/kg of body weight/day given orally for 3 days, while (-)-(R)-PQ was well tolerated. In a novel mouse model of hemolytic anemia associated with human G6PD deficiency, it was also demonstrated that (-)-(R)-PQ was less hemolytic than (+)-(S)-PQ for the G6PD-deficient human red cells engrafted in the NOD-SCID mice. All these data suggest that while (+)-(S)-PQ shows greater potency in terms of antiparasitic efficacy in rodents, it is also more hematotoxic than (-)-(R)-PQ in mice and dogs. Activity and toxicity differences of PQ enantiomers in different species can be attributed to their different pharmacokinetic and metabolic profiles. Taken together, these studies suggest that (-)-(R)-PQ may have a better safety margin than the racemate in human.

  17. Accumulation dynamics of chlordanes and their enantiomers in cockerels (Gallus gallus) after oral exposure.

    PubMed

    Lu, Zhijiang; Xue, Miao; Shen, Guofeng; Li, Kaiyang; Li, Xiqing; Wang, Xilong; Tao, Shu

    2011-09-15

    After a single oral exposure of technical chlordane, levels of cis-chlordane (CC), trans-chlordane (TC), heptachlor (HEP), heptachlorepoxide (HEPX), and oxychlordane (OXY) were determined in gastrointestinal residues, droppings, and various tissues of cockerels at times of 60, 120, 160, 200, 300, 500, 1000, and 2000 min. Over 98% of CC and TC were found to be bioaccessible; only 1.1% of CC and TC were directly excreted through droppings without further biotransformation. According to the single-compartment toxicokinetic modeling, CC and TC shared similar absorption rates in the whole body while TC showed a slightly more rapid elimination rate, with a half-life of 13.4 h for CC and 12.5 h for TC. The metabolites HEPX and OXY appeared quickly in tissues 60 min after exposure and were mainly accumulated in fat and liver tissues. Concentrations of CC, TC, and HEP in cockerel tissues roughly followed the order as fat > intestine > skin > liver> brain > muscle > blood. Levels of CC, TC, and HEP in various tissues showed significant correlation with the lipid contents of the tissues (p < 0.05) for samples beginning 500 min after exposure. A multicompartment toxicokinetic model was developed to characterize the accumulation dynamics of CC and TC in the various tissues. All tissues of cockerels enantioselectively accumulated (-)-CC and (+)-TC, and fat, skin, and liver tissues showed a relatively stronger capacity of enantioenrichment. The enantiomer fractions (EFs) of droppings remained nearly racemic at first but gradually decreased to less than 0.5 for CC and increased to more than 0.5 for TC, which could rule out enantioselective absorption and excretion of CC and TC in cockerels. The one-compartment toxicokinetic model was applied to the individual enantiomers of CC and TC. Different elimination rates but similar absorption rates were observed between the enantiomers for both CC and TC. PMID:21823571

  18. Binding of naproxen enantiomers to human serum albumin studied by fluorescence and room-temperature phosphorescence

    NASA Astrophysics Data System (ADS)

    Lammers, Ivonne; Lhiaubet-Vallet, Virginie; Ariese, Freek; Miranda, Miguel A.; Gooijer, Cees

    2013-03-01

    The interaction of the enantiomers of the non-steroidal anti-inflammatory drug naproxen (NPX) with human serum albumin (HSA) has been investigated using fluorescence and phosphorescence spectroscopy in the steady-state and time-resolved mode. The absorption, fluorescence excitation, and fluorescence emission spectra of (S)-NPX and (R)-NPX differ in shape in the presence of HSA, indicating that these enantiomers experience a different environment when bound. In solutions containing 0.2 M KI, complexation with HSA results in a strongly increased NPX fluorescence intensity and a decreased NPX phosphorescence intensity due to the inhibition of the collisional interaction with the heavy atom iodide. Fluorescence intensity curves obtained upon selective excitation of NPX show 8-fold different slopes for bound and free NPX. No significant difference in the binding constants of (3.8 ± 0.6) × 105 M-1 for (S)-NPX and (3.9 ± 0.6) × 105 M-1 for (R)-NPX was found. Furthermore, the addition of NPX quenches the phosphorescence of the single tryptophan in HSA (Trp-214) based on Dexter energy transfer. The short-range nature of this mechanism explains the upward curvature of the Stern-Volmer plot observed for HSA: At low concentrations NPX binds to HSA at a distance from Trp-214 and no quenching occurs, whereas at high NPX concentrations the phosphorescence intensity decreases due to dynamic quenching by NPX diffusing into site I from the bulk solution. The dynamic quenching observed in the Stern-Volmer plots based on the longest phosphorescence lifetime indicates an overall binding constant to HSA of about 3 × 105 M-1 for both enantiomers.

  19. The use of symmetry in enantioselective synthesis: four pairs of chrysene enantiomers prepared from 19-nortestosterone.

    PubMed

    Stastna, Eva; Rath, Nigam P; Covey, Douglas F

    2011-06-21

    Expansion of the D-ring of 19-norsteroids with incorporation of the steroid C-18 methyl group into a newly formed six-membered ring provides easy access to the chrysene ring system. By taking advantage of the symmetry of the chrysene ring system and avoiding meso chrysene intermediates, four optically pure 2,8-difunctionalized (C-2 hydroxyl group and C-8 oxo group) hexadecahydrochrysene diastereomers, and their corresponding optically pure enantiomers were prepared from 19-nortestosterone. The eight chrysene stereoisomers are of interest as starting materials for preparing chrysene analogues of physiologically important neurosteroids.

  20. Annual cycles of organochlorine pesticide enantiomers in Arctic air suggest changing sources and pathways

    NASA Astrophysics Data System (ADS)

    Bidleman, T. F.; Jantunen, L. M.; Hung, H.; Ma, J.; Stern, G. A.; Rosenberg, B.; Racine, J.

    2015-02-01

    Air samples collected during 1994-2000 at the Canadian Arctic air monitoring station Alert (82°30' N, 62°20' W) were analysed by enantiospecific gas chromatography-mass spectrometry for α-hexachlorocyclohexane (α-HCH), trans-chlordane (TC) and cis-chlordane (CC). Results were expressed as enantiomer fractions (EF = peak areas of (+)/[(+) + (-)] enantiomers), where EFs = 0.5, < 0.5 and > 0.5 indicate racemic composition, and preferential depletion of (+) and (-) enantiomers, respectively. Long-term average EFs were close to racemic values for α -HCH (0.504 ± 0.004, n = 197) and CC (0.505 ± 0.004, n = 162), and deviated farther from racemic for TC (0.470 ± 0.013, n = 165). Digital filtration analysis revealed annual cycles of lower α-HCH EFs in summer-fall and higher EFs in winter-spring. These cycles suggest volatilization of partially degraded α-HCH with EF < 0.5 from open water and advection to Alert during the warm season, and background transport of α-HCH with EF > 0.5 during the cold season. The contribution of sea-volatilized α-HCH was only 11% at Alert, vs. 32% at Resolute Bay (74.68° N, 94.90° W) in 1999. EFs of TC also followed annual cycles of lower and higher values in the warm and cold seasons. These were in phase with low and high cycles of the TC/CC ratio (expressed as FTC = TC/(TC+CC)), which suggests greater contribution of microbially "weathered" TC in summer-fall versus winter-spring. CC was closer to racemic than TC and displayed seasonal cycles only in 1997-1998. EF profiles are likely to change with rising contribution of secondary emission sources, weathering of residues in the environment, and loss of ice cover in the Arctic. Enantiomer-specific analysis could provide added forensic capability to air monitoring programs.

  1. [Plasma ibuprofen enantiomers and their pharmacokinetics in Beagle dogs determined by HPLC].

    PubMed

    Wang, Hong-yan; Kong, Ai-ying; Yang, Bo; Yan, Liang-ping; Di, Xin

    2015-12-01

    A chiral high-performance liquid chromatography method was developed for the simultaneous determination of ibuprofen enantiomers in dog plasma. It was used to study the pharmacokinetics in the Beagle dog after intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen. Ketoprofen was chosen as the internal standard. After a simple precipitation using methanol as the precipitating solvent, both analytes and IS were separated on a Kromasil 100-5CHI-TBB chiral column (250 mm x4.6 mm, 5 μm) with isocratic elution using acetonitrile - 20 mmol x L(-1) phosphate buffer (pH 3.0, containing 5% methanol) (6 : 4) as the mobile phase. The detection wavelength was 220 nm. Liner calibration curves for both of the ibuprofen enantiomers were over the concentration range from 0.5 to 50 μg x mL(-1) with a lower limit of quantification of 0.5 μg x mL(-1), the accuracies were all in standard ranges. The intra- and inter- assay precisions were all below 7%. The recovery rate was 93.1% to 100.4%. The experiments proved that the method was simple, rapid and sensitive. It can be used in the quantitative determination of ibuprofen enantiomers in dog plasma. The method was used to determine the concentration of ibuprofen enantiomers in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen (9 mg x kg(-1)) and the pharmacokinetics parameters were calculated based on the concentration-time curves. The C(max) of S-ibuprofen in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen were 30.8 ± 4.7, 46.1 ± 5.9 and 20.0 ± 2.6 μg x mL(-1), respectively. In terms of the exposure of active ingredient, it revealed a significant difference between the administration of S-ibuprofen and the other two groups. The systematical R- to S- chiral inversion was discussed. Comparing the pharmacokinetic parameters at different doses, chiral inversion were 70.1% ± 36.6% and 76

  2. Two pairs of farnesyl phenolic enantiomers as natural nitric oxide inhibitors from Ganoderma sinense.

    PubMed

    Wang, Meng; Wang, Fei; Xu, Feng; Ding, Li-Qin; Zhang, Qian; Li, Hui-Xiang; Zhao, Feng; Wang, Li-Qing; Zhu, Li-Han; Chen, Li-Xia; Qiu, Feng

    2016-07-15

    Four new farnesyl phenolic compounds, ganosinensols A-D (1-4) were isolated from the 95% EtOH extract of the fruiting bodies of Ganoderma sinense. Two pairs of enantiomers, 1/2, and 3/4 were isolated by HPLC using a Daicel Chiralpak IE column. Their structures were elucidated from extensive spectroscopic analyses and comparison with literature data. The absolute configurations of 1-4 were assigned by ECD spectra. All of these isolated compounds showed potent inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages, with IC50 values from 1.15 to 2.26μM. PMID:27256914

  3. Biannual cycles of organochlorine pesticide enantiomers in arctic air suggest changing sources and pathways

    NASA Astrophysics Data System (ADS)

    Bidleman, T. F.; Jantunen, L. M.; Hung, H.; Ma, J.; Stern, G. A.; Rosenberg, B.; Racine, J.

    2014-09-01

    Air samples collected during 1994-2000 at the Canadian arctic air monitoring station Alert (82°30' N, 62°20' W) were analyzed by enantiospecific gas chromatography - mass spectrometry for α-hexachlorocyclohexane (α-HCH), trans-chlordane (TC) and cis-chlordane (CC). Results were expressed as enantiomer fractions (EF = quantities of (+)/[(+) + (-)] enantiomers), where EFs = 0.5, <0.5 and >0.5 indicate racemic composition, and preferential depletion of (+) and (-) enantiomers, respectively. Long-term average EFs were close to racemic values for α-HCH (0.504 ± 0.004, n = 197) and CC (0.505 ± 0.004, n = 162), and deviated farther from racemic for TC (0.470 ± 0.013, n = 165). Digital filtration analysis revealed biannual cycles of lower α-HCH EFs in summer-fall and higher EFs in winter-spring. These cycles suggest volatilization of partially degraded α-HCH with EF < 0.5 from open water and advection to Alert during the warm season, and background transport of α-HCH with EF > 0.5 during the cold season. The contribution of sea-volatilized α-HCH was only 11% at Alert, vs. 32% at Resolute Bay (74.68° N, 94.90° W) in 1999. EFs of TC also followed biannual cycles of lower and higher values in the warm and cold seasons. These were in phase with low and high cycles of the TC/CC ratio (expressed as FTC = TC/(TC + CC)), which suggests greater contribution of microbially "weathered" TC in summer-fall vs. winter-spring. CC was closer to racemic than TC and displayed seasonal cycles only in 1997-1998. EF profiles are likely to change with rising contribution of secondary emission sources, weathering of residues in the environment, and loss of ice cover in the Arctic. Enantiomer-specific analysis could provide added forensic capability to air monitoring programs.

  4. Stereospecificity of the sensory irritation receptor for nonreactive chemicals illustrated by pinene enantiomers.

    PubMed

    Kasanen, J P; Pasanen, A L; Pasanen, P; Liesivuori, J; Kosma, V M; Alarie, Y

    1998-01-01

    To clarify the existence of a receptor protein for sensory irritants in trigeminal nerve endings, D- [i.e. (+)] and L- [i.e. (-)] enantiomers of alpha- and beta-pinene as models of nonreactive chemicals were evaluated for their potency in outbred OF1 and NIH/S mice using ASTM E981-84 bioassay. All pinenes possess sensory irritation properties and also induced sedation and signs of anaesthesia but had no pulmonary irritation effects. According to the ratio of RD50 (i.e. concentration which causes a 50% decrease in respiratory rate,f) and vapour pressure (Po), all pinenes are nonreactive chemicals. For nonreactive chemicals, Po and olive oil-gas partition (Loil) can be used to estimate their potency as sensory irritant. Thus, for enantiomers with identical physicochemical properties, the estimated RD50 values are the same. In addition, although alpha- and beta-pinene do not have identical Po and Loil values, their estimated potencies are quite close. However, the experimental results showed that D-enantiomers of pinenes were the most potent as sensory irritants and a difference in potency also exists between alpha- and beta-pinene. RD50 for D-enantiomers of alpha- and beta-pinene were almost equal, 1053 ppm and 1279 ppm in OF1 strain and 1107 ppm and 1419 ppm in NIH/S strain, respectively. Values differed by a factor of approximately 4 to 5 from L-beta-pinene for which the RD50 was 4663 ppm in OF1 and 5811 ppm in NIH/S mice. RD50 could not be determined for L-alpha-pinene; this pinene was almost inactive. D-alpha-pinene seems to best fit the receptor because its experimental RD50 was one-half of the estimated value while for D-beta-pinene those values were equal. On the contrary, L-beta-pinene was about 3 to 4 times less potent than estimated. L-alpha-pinene was only slightly active although it was estimated to be as potent as D-alpha-pinene. The remarkable difference in potency between L-enantiometers is most likely due to a structural difference between alpha- and

  5. Vibrational spectra, NMR and theoretical studies of the enantiomers and rotamers of alpha-cypermethrin.

    PubMed

    Jubert, Alicia H; Alegre, María L; Diez, Reinaldo Pis; Pomilio, Alicia B; Szewczuk, Víctor D

    2007-04-01

    NMR, infrared and Raman vibrational spectra of alpha-cypermethrin have been measured at room temperature. Infrared spectra were also recorded to low temperature. The spectra were analyzed by means of ab initio calculations. The conformational space of both enantiomers and some rotamers A, B and C of alpha-cypermethrin has been scanned using molecular dynamics and complemented with functional density calculations that optimize the geometry of the lowest-energy conformers of each species as obtained in the simulations. The vibrational frequencies and the 1H and 13C NMR chemical shifts were assigned using functional density calculations. The molecular electrostatic potential maps were obtained and analyzed.

  6. Vibrational spectra, NMR and theoretical studies of the enantiomers and rotamers of alpha-cypermethrin

    NASA Astrophysics Data System (ADS)

    Jubert, Alicia H.; Alegre, María L.; Diez, Reinaldo Pis; Pomilio, Alicia B.; Szewczuk, Víctor D.

    2007-04-01

    NMR, infrared and Raman vibrational spectra of alpha-cypermethrin have been measured at room temperature. Infrared spectra were also recorded to low temperature. The spectra were analyzed by means of ab initio calculations. The conformational space of both enantiomers and some rotamers A, B and C of alpha-cypermethrin has been scanned using molecular dynamics and complemented with functional density calculations that optimize the geometry of the lowest-energy conformers of each species as obtained in the simulations. The vibrational frequencies and the 1H and 13C NMR chemical shifts were assigned using functional density calculations. The molecular electrostatic potential maps were obtained and analyzed.

  7. β-Cyclodextrin as the suitable molecular container for isopulegol enantiomers.

    PubMed

    Ceborska, Magdalena; Szwed, Kamila; Suwinska, Kinga

    2013-09-12

    Isopulegol, an insoluble in water and highly volatile compound, due to its neuroactive properties is a potentially important agent for medical applications. Formation of "host-guest" molecular complexes with cyclodextrins would lead to the increase of its water solubility and bioavailability. Interactions between native cyclodextrins (α, β and γ) and isopulegol enantiomers were studied in solution proving the formation of inclusion complexes for β- and γ-cyclodextrins. For the more stable complexes with β-cyclodextrin crystal structures were obtained showing the formation of molecular capsules forming molecular container able to accommodate two guest molecules. PMID:23911483

  8. [Synthesis and applications of chiral metal-organic framework in the selective separation of enantiomers].

    PubMed

    Qi, Xiaoyue; Li, Xianjiang; Bai, Yu; Liu, Huwei

    2016-01-01

    Chirality is a universal phenomenon in nature. Chiral separation is vitally important in drug development, agricultural chemistry, pharmacology, environmental science, biology and many other fields. Chiral metal-organic frameworks (MOFs) are a new group of porous materials with special topology and designable pore structures, as well as their high specific surface area, porosity, excellent thermal stability, solvent resistance, etc. Thus, chiral MOFs are promising with various applications in the field of analytical chemistry. This review summarizes the synthesis strategies of chiral MOFs and their applications in the selective separation of enantiomers, as well as related mechanism.

  9. Chromatographic resolution of the enantiomers of a pharmaceutical intermediate from the milligram to the kilogram scale.

    PubMed

    Miller, L; Orihuela, C; Fronek, R; Honda, D; Dapremont, O

    1999-07-23

    The preparative chromatographic resolution of racemic mixtures is rapidly becoming a standard approach for the generation of enantiomers in pharmaceutical R&D. This paper will discuss the optical resolution of a pharmaceutical intermediate as the separation is scaled up from the milligram to the kilogram scale. Difficulties encountered and their solutions at each scale will be discussed. In addition, the exploration of Simulated Moving Bed (SMB) for the separation will also be discussed. Finally, a comparison of the productivities and solvent consumption for each method and scale will be presented.

  10. [Plasma ibuprofen enantiomers and their pharmacokinetics in Beagle dogs determined by HPLC].

    PubMed

    Wang, Hong-yan; Kong, Ai-ying; Yang, Bo; Yan, Liang-ping; Di, Xin

    2015-12-01

    A chiral high-performance liquid chromatography method was developed for the simultaneous determination of ibuprofen enantiomers in dog plasma. It was used to study the pharmacokinetics in the Beagle dog after intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen. Ketoprofen was chosen as the internal standard. After a simple precipitation using methanol as the precipitating solvent, both analytes and IS were separated on a Kromasil 100-5CHI-TBB chiral column (250 mm x4.6 mm, 5 μm) with isocratic elution using acetonitrile - 20 mmol x L(-1) phosphate buffer (pH 3.0, containing 5% methanol) (6 : 4) as the mobile phase. The detection wavelength was 220 nm. Liner calibration curves for both of the ibuprofen enantiomers were over the concentration range from 0.5 to 50 μg x mL(-1) with a lower limit of quantification of 0.5 μg x mL(-1), the accuracies were all in standard ranges. The intra- and inter- assay precisions were all below 7%. The recovery rate was 93.1% to 100.4%. The experiments proved that the method was simple, rapid and sensitive. It can be used in the quantitative determination of ibuprofen enantiomers in dog plasma. The method was used to determine the concentration of ibuprofen enantiomers in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen (9 mg x kg(-1)) and the pharmacokinetics parameters were calculated based on the concentration-time curves. The C(max) of S-ibuprofen in Beagle dog plasma after a single intravenous administration of racemic-ibuprofen, S-ibuprofen and R-ibuprofen were 30.8 ± 4.7, 46.1 ± 5.9 and 20.0 ± 2.6 μg x mL(-1), respectively. In terms of the exposure of active ingredient, it revealed a significant difference between the administration of S-ibuprofen and the other two groups. The systematical R- to S- chiral inversion was discussed. Comparing the pharmacokinetic parameters at different doses, chiral inversion were 70.1% ± 36.6% and 76

  11. Chromatographic separation of phenylpropanol enantiomers on a quinidine carbamate-type chiral stationary phase

    SciTech Connect

    Asnin, Leonid; Guiochon, Georges A

    2005-07-01

    The retention and the separation of the enantiomers of 1-phenylpropanol (1PP), 2-phenylpropanol (2PP), and 3-chloro-1-phenylpropanol (3CPP) on silica-bonded quinidine carbamate under normal phase HPLC conditions were investigated. A relatively high selectivity of the stationary phase for 3CPP and 1PP ({alpha} {approx} 1.07-1.09) was achieved with eluents containing ethyl acetate as the polar modifier. These mobile phases were examined in detail. Based on the set of chromatographic and thermodynamic data collected, conclusions regarding the mechanism of enantioselectivity and the structure of the selector chiral center are made.

  12. Validation of a Chiral Liquid Chromatographic Method for the Degradation Behavior of Flumequine Enantiomers in Mariculture Pond Water.

    PubMed

    Wang, Yan-Fei; Gao, Xiao-Feng; Jin, Huo-Xi; Wang, Yang-Guang; Wu, Wei-Jian; Ouyang, Xiao-Kun

    2016-09-01

    In this work, flumequine (FLU) enantiomers were separated using a Chiralpak OD-H column, with n-hexane-ethanol (20:80, v/v) as the mobile phase at a flow rate of 0.6 mL/min. Solid phase extraction (SPE) was used for cleanup and enrichment. The limit of detection, limit of quantitation, linearity, precision, and intra/interday variation of the chiral high-performance liquid chromatography (HPLC) method were determined. The developed method was then applied to investigate the degradation behavior of FLU enantiomers in mariculture pond water samples. The results showed that the degradation of FLU enantiomers under natural, sterile, or dark conditions was not enantioselective. Chirality 28:649-655, 2016. © 2016 Wiley Periodicals, Inc. PMID:27483447

  13. Synthesis and Characterization of Magnetic Molecularly Imprinted Polymer for the Enrichment of Ofloxacin Enantiomers in Fish Samples.

    PubMed

    Wang, Yan-Fei; Jin, Huo-Xi; Wang, Yang-Guang; Yang, Li-Ye; OuYang, Xiao-Kun; Wu, Wei-Jian

    2016-01-01

    A new method for the isolation and enrichment of ofloxacin enantiomers from fish samples was developed using magnetic molecularly imprinted polymers (MMIPs). These polymers can be easily collected and rapidly separated using an external magnetic field, and also exhibit a high specific recognition for ofloxacin enantiomers. The preparation of amino-functionalized MMIPs was carried out via suspension polymerization and a ring-opening reaction using rac-ofloxacin as a template, ethylenediamine as an active group, glycidyl methacrylate and methyl methacrylate as functional monomers, divinylbenzene as a cross-linker, and Fe₃O₄ nanoparticles as magnetic cores. The characteristics of the MMIPs were assessed using transmission electron microscopy (TEM), X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and vibrating sample magnetometer (VSM) measurements. Furthermore, the adsorption properties were determined using Langmuir and Freundlich isotherm models. The conditions for use of these MMIPs as magnetic solid-phase extraction (MSPE) sorbents, including pH, adsorption time, desorption time, and eluent, were investigated in detail. An extraction method using MMIPs coupled with high performance liquid chromatography (HPLC) was developed for the determination of ofloxacin enantiomers in fish samples. The limits of quantitation (LOQ) for the developed method were 0.059 and 0.067 μg∙mL(-1) for levofloxacin and dextrofloxacin, respectively. The recovery of ofloxacin enantiomers ranged from 79.2% ± 5.6% to 84.4% ± 4.6% and ofloxacin enantiomers had good linear relationships within the concentration range of 0.25-5.0 μg∙mL(-1) (R² > 0.999). The obtained results demonstrate that MSPE-HPLC is a promising approach for preconcentration, purification, and simultaneous separation of ofloxacin enantiomers in biomatrix samples. PMID:27428943

  14. Simultaneous determination of chiral pesticide flufiprole enantiomers in vegetables, fruits, and soil by high-performance liquid chromatography.

    PubMed

    Tian, Mingming; Zhang, Qing; Shi, Haiyan; Gao, Beibei; Hua, Xiude; Wang, Minghua

    2015-05-01

    A simple and reliable method for the simultaneous determination of chiral pesticide flufiprole enantiomers using high-performance liquid chromatography has been established. The separation and determination were performed using reversed-phase chromatography on a carbamoyl-cellulose-type chiral stationary phase, a Lux Cellulose-2 column. The effects of different mobile phase composition on separation were discussed. The absolute configuration of flufiprole enantiomers was measured through the combination of experimental and predicted ECD spectra. An Alumina-N solid-phase extraction (SPE) column was used in the cleanup of the vegetables, fruits, and soil samples. The method was evaluated by the specificity, matrix effect, linearity, precision, accuracy and stability. The mean recoveries of two enantiomers ranged from 86.8 to 98.9 %, with 1.1-6.4 % intra-day relative standard deviation (RSD) and 1.2 to 5.8 % inter-day RSD. Good linearity (R (2) > 0.998) was obtained for all analyte matrix calibration curves within the range of 0.2-20 mg L(-1). The limit of detection for two enantiomers in the six matrices was 0.007-0.008 mg kg(-1), whereas the limit of quantification of two enantiomers in fruits, vegetables, and soil was 0.021-0.025 mg kg(-1). The results confirmed that this method was convenient and accurate for the simultaneous determination of flufiprole enantiomers in food and environmental samples. PMID:25736242

  15. Synthesis and Characterization of Magnetic Molecularly Imprinted Polymer for the Enrichment of Ofloxacin Enantiomers in Fish Samples.

    PubMed

    Wang, Yan-Fei; Jin, Huo-Xi; Wang, Yang-Guang; Yang, Li-Ye; OuYang, Xiao-Kun; Wu, Wei-Jian

    2016-07-14

    A new method for the isolation and enrichment of ofloxacin enantiomers from fish samples was developed using magnetic molecularly imprinted polymers (MMIPs). These polymers can be easily collected and rapidly separated using an external magnetic field, and also exhibit a high specific recognition for ofloxacin enantiomers. The preparation of amino-functionalized MMIPs was carried out via suspension polymerization and a ring-opening reaction using rac-ofloxacin as a template, ethylenediamine as an active group, glycidyl methacrylate and methyl methacrylate as functional monomers, divinylbenzene as a cross-linker, and Fe₃O₄ nanoparticles as magnetic cores. The characteristics of the MMIPs were assessed using transmission electron microscopy (TEM), X-ray powder diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR), and vibrating sample magnetometer (VSM) measurements. Furthermore, the adsorption properties were determined using Langmuir and Freundlich isotherm models. The conditions for use of these MMIPs as magnetic solid-phase extraction (MSPE) sorbents, including pH, adsorption time, desorption time, and eluent, were investigated in detail. An extraction method using MMIPs coupled with high performance liquid chromatography (HPLC) was developed for the determination of ofloxacin enantiomers in fish samples. The limits of quantitation (LOQ) for the developed method were 0.059 and 0.067 μg∙mL(-1) for levofloxacin and dextrofloxacin, respectively. The recovery of ofloxacin enantiomers ranged from 79.2% ± 5.6% to 84.4% ± 4.6% and ofloxacin enantiomers had good linear relationships within the concentration range of 0.25-5.0 μg∙mL(-1) (R² > 0.999). The obtained results demonstrate that MSPE-HPLC is a promising approach for preconcentration, purification, and simultaneous separation of ofloxacin enantiomers in biomatrix samples.

  16. Sulfoxide-TFAA and nucleophile combination as new reagent for aliphatic C-H functionalization at indole 2α-position.

    PubMed

    Tayu, Masanori; Higuchi, Kazuhiro; Inaba, Masato; Kawasaki, Tomomi

    2013-01-21

    Aliphatic C-H functionalization at indole 2α-position mediated by acyloxythionium species 1 generated from sulfoxide and acid anhydride has been developed. The combination of sulfoxide and TFAA with O-, N- and C-nucleophiles enabled introduction of various substituents in a one-pot procedure. Especially on utilizing DMSO, the combination provided a practical and efficient method for the synthesis of a wide range of 2α-substituted indoles.

  17. Visualisation of enantiomers via insertion of a BIRD module in X H correlation experiments in chiral liquid crystal solvent

    NASA Astrophysics Data System (ADS)

    Ziani, L.; Courtieu, J.; Merlet, D.

    2006-11-01

    Several 13C- 1H NMR techniques are derived simplifying the visualisation of enantiomers in chiral ordering solvents. They proceed through various heteronuclear 2D experiments where a bilinear rotation decoupling sequence (BIRD) is inserted in the middle of the t1 evolution period. In this way, the small couplings are refocused while the large couplings are preserved. The methods allow extracting precise values of one-bond carbon-proton residual dipolar couplings for each enantiomer out of unresolved proton-coupled 13C or carbon-coupled 1H spectra. Illustrative examples are analysed and discussed using various pulse sequences.

  18. Bis(dimethyl sulfoxide-κO)bis­(mercapto­acetato-κ2 O,S)tin(IV)

    PubMed Central

    Song, Li

    2009-01-01

    In the title compound, [Sn(C2H2O2S)2(C2H6OS)2], the mercaptoacetato ligands chelate to SnIV through S and one O atoms. The metal centre is also coordinated by two dimethyl sulfoxide (DMSO) ligands through the O atom, leading to an overall distorted octahedral coordination environment for the SnIV atom. The mol­ecular adduct lies on a twofold rotation axis. PMID:21578179

  19. Iodine-Catalyzed Cross Dehydrogenative Coupling Reaction: A Regioselective Sulfenylation of Imidazoheterocycles Using Dimethyl Sulfoxide as an Oxidant.

    PubMed

    Siddaraju, Yogesh; Prabhu, Kandikere Ramaiah

    2016-09-01

    A regioselective formation of C-S bonds has been achieved using a cross dehydrogenative coupling (CDC) protocol using iodine as a catalyst and dimethyl sulfoxide as an oxidant under green chemistry conditions. This strategy employs the reaction of easily available heterocyclic thiols or thiones with imidazoheterocycles. This protocol provides an efficient, mild, and inexpensive method for sulfenylation of imidazoheterocycles with a diverse range of heterocyclic thiols and heterocyclic thiones. PMID:27490357

  20. Variation of Spectral Characteristics of Coelenteramide-Containing Fluorescent Protein from Obelia Longissima Exposed to Dimethyl Sulfoxide

    NASA Astrophysics Data System (ADS)

    Petrova, A. S.; Alieva, R. R.; Belogurova, N. V.; Tirranen, L. S.; Kudryasheva, N. S.

    2016-08-01

    Effect of dimethyl sulfoxide (DMSO), a widespread biomedical agent, on spectral-luminescent characteristics of coelenteramide-containing fluorescent protein - discharged obelin - is investigated. Contributions of violet and blue-green spectral components to fluorescence of discharged obelin are elucidated and characterized at different photoexcitation energies. Dependences of these contributions on the DMSO concentration are presented. Spectral changes are related to the destructive effect of DMSO on fluorescent protein and decreasing efficiency of proton transfer to electronically excited states of fluorophore.

  1. Charge-transfer complexation and photoreduction of viologen derivatives bearing the para-substituted benzophenone group in dimethyl sulfoxide

    SciTech Connect

    Tanaka, Chiho; Nambu, Yoko; Endo, Takeshi

    1992-08-20

    New viologen derivatives having the various para-substituted benzophenone groups connected with a -(CH{sub 2}){sub 3}-linkage were effectively photoreduced by dimethyl sulfoxide by the intramolecular charge transfer complex formation between the viologen and benzophenone groups through effective stacking. The photoreduction was enhanced by the introduction of electron-donating para-substituents on the benzophenone units which were favorable for the intramolecular charge transfer complexation. 6 refs., 5 figs.

  2. Effect of basic and acidic additives on the separation of some basic drug enantiomers on polysaccharide-based chiral columns with acetonitrile as mobile phase.

    PubMed

    Gogaladze, Khatuna; Chankvetadze, Lali; Tsintsadze, Maia; Farkas, Tivadar; Chankvetadze, Bezhan

    2015-03-01

    The separation of enantiomers of 16 basic drugs was studied using polysaccharide-based chiral selectors and acetonitrile as mobile phase with emphasis on the role of basic and acidic additives on the separation and elution order of enantiomers. Out of the studied chiral selectors, amylose phenylcarbamate-based ones more often showed a chiral recognition ability compared to cellulose phenylcarbamate derivatives. An interesting effect was observed with formic acid as additive on enantiomer resolution and enantiomer elution order for some basic drugs. Thus, for instance, the enantioseparation of several β-blockers (atenolol, sotalol, toliprolol) improved not only by the addition of a more conventional basic additive to the mobile phase, but also by the addition of an acidic additive. Moreover, an opposite elution order of enantiomers was observed depending on the nature of the additive (basic or acidic) in the mobile phase.

  3. Cloning the expression of a mammalian gene involved in the reduction of methionine sulfoxide residues in proteins.

    PubMed Central

    Moskovitz, J; Weissbach, H; Brot, N

    1996-01-01

    An enzyme that reduces methionine sulfoxide [Met(O)] residues in proteins [peptide Met(O) reductase (MsrA), EC 1.8.4.6; originally identified in Escherichia coli] was purified from bovine liver, and the cDNA encoding this enzyme was cloned and sequenced. The mammalian homologue of E. coli msrA (also called pmsR) cDNA encodes a protein of 255 amino acids with a calculated molecular mass of 25,846 Da. This protein has 61% identity with the E. coli MsrA throughout a region encompassing a 199-amino acid overlap. The protein has been overexpressed in E. coli and purified to homogeneity. The mammalian recombinant MsrA can use as substrate, proteins containing Met(O) as well as other organic compounds that contain an alkyl sulfoxide group such as N-acetylMet(O), Met(O), and dimethyl sulfoxide. Northern analysis of rat tissue extracts showed that rat msrA mRNA is present in a variety of organs with the highest level found in kidney. This is consistent with the observation that kidney extracts also contained the highest level of enzyme activity. Images Fig. 3 Fig. 5 PMID:8700890

  4. Thermochemistry of 1,3-dithiacyclohexane 1-oxide (1,3-dithiane sulfoxide): calorimetric and computational study.

    PubMed

    Roux, María Victoria; Temprado, Manuel; Jiménez, Pilar; Dávalos, Juan Z; Notario, Rafael; Martín-Valcárcel, Gloria; Garrido, Leoncio; Guzmán-Mejía, Ramón; Juaristi, Eusebio

    2004-08-01

    The enthalpies of combustion and sublimation of 1,3-dithiacyclohexane 1-oxide (1,3-dithiane sulfoxide, 2) were measured by a rotating-bomb combustion calorimeter and the Knudsen effusion technique, and the gas-phase enthalpy of formation was determined, DeltafH degrees m(g) = -98.0 +/- 1.9 kJ mol(-1). This value is not as large (negative) as could have been expected from comparison with thermochemical data available for the thiane/thiane oxide reference system. High-level ab initio molecular orbital calculations at the MP2(FULL)/6-31G(3df,2p) level were performed, and the optimized molecular and electronic structures of 2 afforded valuable information on (1) the relative conformational energies of 2-axial and 2-equatorial--the latter being 7.1 kJ mol(-1) more stable than 2-axial, (2) the possible involvement of nS --> sigma*(C-S(O)) hyperconjugation in 2-equatorial, (3) the lack of computational evidence for sigma(S-C) --> sigma*(S-O) stereoelectronic interaction in 2-equatorial, and (4) the relevance of a repulsive electrostatic interaction between sulfur atoms in 1,3-dithiane sulfoxide, which apparently counterbalances any nS --> sigma*(C-S(O)) stabilizing hyperconjugative interaction and accounts for the lower than expected enthalpy of formation for sulfoxide 2. PMID:15287796

  5. Studies of a Novel Cysteine Sulfoxide Lyase from Petiveria alliacea: The First Heteromeric Alliinase1[W][OA

    PubMed Central

    Musah, Rabi A.; He, Quan; Kubec, Roman; Jadhav, Abhijit

    2009-01-01

    A novel alliinase (EC 4.4.1.4) was detected and purified from the roots of the Amazonian medicinal plant Petiveria alliacea. The isolated enzyme is a heteropentameric glycoprotein composed of two α-subunits (68.1 kD each), one β-subunit (56.0 kD), one γ-subunit (24.8 kD), and one δ-subunit (13.9 kD). The two α-subunits are connected by a disulfide bridge, and both α- and β-subunits are glycosylated. The enzyme has an isoelectric point of 4.78 and pH and temperature optima of 8.0 and approximately 52°C, respectively. Its activation energy with its natural substrate S-benzyl-l-cysteine sulfoxide is 64.6 kJ mol−1. Kinetic studies showed that both Km and Vmax vary as a function of substrate structure, with the most preferred substrates being the naturally occurring P. alliacea compounds S-benzyl-l-cysteine sulfoxide and S-2-hydroxyethyl-l-cysteine sulfoxide. The alliinase reacts with these substrates to produce S-benzyl phenylmethanethiosulfinate and S-(2-hydroxyethyl) 2-hydroxyethanethiosulfinate, respectively. PMID:19789290

  6. Determination of methiocarb and its degradation products, methiocarb sulfoxide and methiocarb sulfone, in bananas using QuEChERS extraction.

    PubMed

    Plácido, Alexandra; Paíga, Paula; Lopes, David H; Correia, Manuela; Delerue-Matos, Cristina

    2013-01-16

    The present work describes the development of an analytical method for the determination of methiocarb and its degradation products (methiocarb sulfoxide and methiocarb sulfone) in banana samples, using the QuEChERS (quick, easy, cheap, effective, rugged, and safe) procedure followed by liquid chromatography coupled to photodiode array detector (LC-PAD). Calibration curves were linear in the range of 0.5-10 mg L⁻¹ for all compounds studied. The average recoveries, measured at 0.1 mg kg⁻¹ wet weight, were 92.0 (RSD = 1.8%, n = 3), 84.0 (RSD = 3.9%, n = 3), and 95.2% (RSD = 1.9%, n = 3) for methiocarb sulfoxide, methiocarb sulfone, and methiocarb, respectively. Banana samples treated with methiocarb were collected from an experimental field. The developed method was applied to the analysis of 24 samples (peel and pulp) and to 5 banana pulp samples. Generally, the highest levels were found for methiocarb sulfoxide and methiocarb. Methiocarb sulfone levels were below the limit of quantification, except in one sample (not detected).

  7. Methionine sulfoxide profiling of milk proteins to assess the influence of lipids on protein oxidation in milk.

    PubMed

    Wüst, Johannes; Pischetsrieder, Monika

    2016-06-15

    Thermal treatment of milk and milk products leads to protein oxidation, mainly the formation of methionine sulfoxide. Reactive oxygen species, responsible for the oxidation, can be generated by Maillard reaction, autoxidation of sugars, or lipid peroxidation. The present study investigated the influence of milk fat on methionine oxidation in milk. For this purpose, quantitative methionine sulfoxide profiling of all ten methionine residues of β-lactoglobulin, α-lactalbumin, and αs1-casein was carried out by ultrahigh-performance liquid chromatography-electrospray ionization tandem mass spectrometry with scheduled multiple reaction monitoring (UHPLC-ESI-MS/MS-sMRM). Analysis of defatted and regular raw milk samples after heating for up to 8 min at 120 °C and analysis of ultrahigh-temperature milk samples with 0.1%, 1.5%, and 3.5% fat revealed that methionine oxidation of the five residues of the whey proteins and of residues M 123, M 135, and M 196 of αs1-casein was not affected or even suppressed in the presence of milk fat. Only the oxidation of residues M 54 and M 60 of αs1-casein was promoted by lipids. In evaporated milk samples, formation of methionine sulfoxide was hardly influenced by the fat content of the samples. Thus, it can be concluded that lipid oxidation products are not the major cause of methionine oxidation in milk.

  8. Resveratrol preconditioning increases methionine sulfoxide reductases A expression and enhances resistance of human neuroblastoma cells to neurotoxins.

    PubMed

    Wu, Peng-Fei; Xie, Na; Zhang, Juan-Juan; Guan, Xin-Lei; Zhou, Jun; Long, Li-Hong; Li, Yuan-Long; Xiong, Qiu-Ju; Zeng, Jian-Hua; Wang, Fang; Chen, Jian-Guo

    2013-06-01

    Methionine sulfoxide reductases A (MsrA) has been postulated to act as a catalytic antioxidant system involved in the protection of oxidative stress-induced cell injury. Recently, attention has turned to MsrA in coupling with the pathology of Parkinson's disease, which is closely related to neurotoxins that cause dopaminergic neuron degeneration. Here, we firstly provided evidence that pretreatment with a natural polyphenol resveratrol (RSV) up-regulated the expression of MsrA in human neuroblastoma SH-SY5Y cells. It was also observed that the expression and nuclear translocation of forkhead box group O 3a (FOXO3a), a transcription factor that activates the human MsrA promoter, increased after RSV pretreatment. Nicotinamide , an inhibitor of silent information regulator 1 (SIRT1), prevented RSV-induced elevation of FOXO3a and MsrA expression, indicating that the effect of RSV was mediated by a SIRT1-dependent pathway. RSV preconditioning increased methionine sulfoxide(MetO)-reducing activity in SH-SY5Y cells and enhanced their resistance to neurotoxins, including chloramine-T and 1-methyl-4-phenyl-pyridinium. In addition, the enhancement of cell resistance to neurotoxins caused by RSV preconditioning can be largely prevented by MsrA inhibitor dimethyl sulfoxide. Our findings suggest that treatment with polyphenols such as RSV can be used as a potential regulatory strategy for MsrA expression and function.

  9. Thermodynamics of sublimation, crystal lattice energies, and crystal structures of racemates and enantiomers: (+)- and (+/-)-ibuprofen.

    PubMed

    Perlovich, German L; Kurkov, Sergey V; Hansen, Lars Kr; Bauer-Brandl, Annette

    2004-03-01

    Thermodynamic differences between ibuprofen (IBP) racemate and the (+)-enantiomer were studied by X-ray diffraction, thermoanalysis, and crystal energy calculations. The thermodynamic functions of sublimation (as a measure of crystal lattice energy) were obtained by the transpiration method. The sublimation enthalpies (DeltaH(sub)) of (+/-)-IBP and (+)-IBP are 115.8 +/- 0.6 and 107.4 +/- 0.5 kJ. mol(-1), respectively. Using the temperature dependency of the saturated vapor pressure, the relative fractions of enthalpy and entropy of the sublimation process were calculated, and the sublimation process for both the racemate and the enantiomer was found to be enthalpy driven (62%). Two different force fields, Mayo et al. (M) and Gavezzotti (G), were used for comparative analysis of crystal lattice energies. Both force fields revealed that the van der Waals term contributes more to the packing energy in (+)-IBP than in (+/-)-IBP. The hydrogen bonding energy, however, contributes at 29.7 and 32.3% to the total crystal lattice energy in (+)-IBP and (+/-)-IBP (M), respectively. Furthermore, different structure fragments of the IBP molecule were analyzed with respect to their contribution to nonbonded van der Waals interactions. The effect of the C-H distance on the van der Waals term of the crystal lattice energy was also studied.

  10. Racemization of undesired enantiomers: Immobilization of mandelate racemase and application in a fixed bed reactor.

    PubMed

    Wrzosek, Katarzyna; Rivera, Mariel A García; Bettenbrock, Katja; Seidel-Morgenstern, Andreas

    2016-03-01

    Production of optically pure products can be based on simple unselective synthesis of racemic mixtures combined with a subsequent separation of the enantiomers; however, this approach suffers from a 50% yield limitation which can be overcome by racemization of the undesired enantiomer and recycling. Application of biocatalyst for the racemization steps offers an attractive option for high-yield manufacturing of commercially valuable compounds. Our work focuses on exploiting the potential of racemization with immobilized mandelate racemase. Immobilization of crude mandelate racemase via covalent attachment was optimized for two supports: Eupergit(®) CM and CNBr-activated Sepharose 4 Fast Flow. To allow coupling of enzymatic reaction with enantioselective chromatography, a mobile phase composition compatible with both processes was used in enzymatic reactor. Kinetic parameters obtained analyzing experiments carried out in a batch reactor could be successfully used to predict fixed-bed reactor performance. The applicability of the immobilized enzyme and the determined kinetic parameters were validated in transient experiments recording responses to pulse injections of R-mandelic acid. The approach investigated can be used for futher design and optimization of high yield combined resolution processes. The characterized fixed-bed enzymatic reactor can be integrated e.g. with chromatographic single- or multicolumn steps in various configurations.

  11. Enantiomer Discrimintation Illustrated by the High Resolution Crystal Structures of Type 4 Phosphodiesterase

    SciTech Connect

    Huai,Q.; Sun, Y.; Wang, H.; MacDonald, D.; Aspiotis, R.; Robinson, H.; Huang, Z.; Ke, H.

    2006-01-01

    Type 4 phosphodiesterase (PDE4) inhibitors are emerging as new treatments for a number of disorders including asthma and chronic obstructive pulmonary disease. Here we report the biochemical characterization on the second generation inhibitor (+)-1 (L-869298, IC50 = 0.4 nM) and its enantiomer (-)-1 (L-869299, IC50 = 43 nM) and their cocrystal structures with PDE4D at 2.0 Angstroms resolution. Despite the 107-fold affinity difference, both enantiomers interact with the same sets of residues in the rigid active site. The weaker (-)-1 adopts an unfavorable conformation to preserve the pivotal interactions between the Mg-bound waters and the N-oxide of pyridine. These structures support a model in which inhibitors are anchored by the invariant glutamine at one end and the metal-pocket residues at another end. This model provides explanations for most of the observed structure-activity relationship and the metal ion dependency of the catechol-ether based inhibitors and should facilitate their further design.

  12. Quantification of chlorpheniramine maleate enantiomers by ultraviolet spectroscopy and chemometric methods.

    PubMed

    Valderrama, P; Romero, A L; Imamura, P M; Magalhães, I R S; Bonato, P S; Poppi, R J

    2010-05-01

    Chlorpheniramine maleate (CLOR) enantiomers were quantified by ultraviolet spectroscopy and partial least squares regression. The CLOR enantiomers were prepared as inclusion complexes with beta-cyclodextrin and 1-butanol with mole fractions in the range from 50 to 100%. For the multivariate calibration the outliers were detected and excluded and variable selection was performed by interval partial least squares and a genetic algorithm. Figures of merit showed results for accuracy of 3.63 and 2.83% (S)-CLOR for root mean square errors of calibration and prediction, respectively. The ellipse confidence region included the point for the intercept and the slope of 1 and 0, respectively. Precision and analytical sensitivity were 0.57 and 0.50% (S)-CLOR, respectively. The sensitivity, selectivity, adjustment, and signal-to-noise ratio were also determined. The model was validated by a paired t test with the results obtained by high-performance liquid chromatography proposed by the European pharmacopoeia and circular dichroism spectroscopy. The results showed there was no significant difference between the methods at the 95% confidence level, indicating that the proposed method can be used as an alternative to standard procedures for chiral analysis.

  13. Enantiomer fractions of polychlorinated biphenyls in three selected Standard Reference Materials.

    PubMed

    Morrissey, Joshua A; Bleackley, Derek S; Warner, Nicholas A; Wong, Charles S

    2007-01-01

    The enantiomer composition of six chiral polychlorinated biphenyls (PCBs) were measured in three different certified Standard Reference Materials (SRMs) from the US National Institute of Standards and Technology (NIST): SRM 1946 (Lake Superior fish tissue), SRM 1939a (PCB Congeners in Hudson River Sediment), and SRM 2978 (organic contaminants in mussel tissue--Raritan Bay, New Jersey) to aid in quality assurance/quality control methodologies in the study of chiral pollutants in sediments and biota. Enantiomer fractions (EFs) of PCBs 91, 95, 136, 149, 174, and 183 were measured using a suite of chiral columns by gas chromatography/mass spectrometry. Concentrations of target analytes were in agreement with certified values. Target analyte EFs in reference materials were measured precisely (<2% relative standard deviation), indicating the utility of SRM in quality assurance/control methodologies for analyses of chiral compounds in environmental samples. Measured EFs were also in agreement with previously published analyses of similar samples, indicating that similar enantioselective processes were taking place in these environmental matrices. PMID:16777177

  14. Conformational transformation of ascidiacyclamide analogues induced by incorporating enantiomers of phenylalanine, 1-naphthylalanine or 2-naphthylalanine.

    PubMed

    Asano, Akiko; Minoura, Katsuhiko; Yamada, Takeshi; Doi, Mitsunobu

    2016-03-01

    We designed five ascidiacyclamide analogues [cyclo(-Xxx(1) -oxazoline(2) -d-Val(3) -thiazole(4) -l-Ile(5) -oxazoline(6) -d-Val(7) -thiazole(8) -)] incorporating l-1-naphthylalanine (l-1Nal), l-2-naphthylalanine (l-2Nal), d-phenylalanine (d-Phe), d-1-naphthylalanine (d-1Nal) or d-2-naphthylalanine (d-2Nal) into the Xxx(1) position of the peptide. The conformations of these analogues were then examined using (1) H NMR, CD spectroscopy, and X-ray diffraction. These analyses suggested that d-enantiomer-incorporated ASCs [(d-Phe), (d-1Nal), and (d-2Nal)ASC] transformed from the folded to the open structure in solution more easily than l-enantiomer-incorporated ASCs [(l-Phe), (l-1Nal), and (l-2Nal)ASC]. Structural comparison of the two analogues containing isomeric naphthyl groups showed that the 1-naphthyl isomer induced a more stable open structure than the 2-naphthyl isomer. In particular, [d-1Nal]ASC showed the most significant transformation from the folded to the open structure in solution, and exhibited the strongest cytotoxicity toward HL-60 cells. PMID:26856689

  15. Diarylpropionitrile (DPN) Enantiomers: Synthesis and Evaluation of Estrogen Receptor Beta-Selective Ligands

    PubMed Central

    Carroll, Vincent M.; Jeyakumar, M.; Carlson, Kathryn E.; Katzenellenbogen, John A.

    2011-01-01

    Two estrogen receptor (ER) subtypes, ERα and ERβ, mediate the actions of estrogens in diverse reproductive and non-reproductive target tissues. ER subtype-selective ligands, which bind to and activate these subtypes differentially, have proved to be useful in elucidating which actions of estrogens proceed through ERα vs. ERβ. Some of these ligands show potential as novel therapeutic agents. Diarylpropionitrile (DPN), an ERβ selective ligand that we developed, is a chiral molecule, but it has been studied almost exclusively as the racemic mixture (rac-DPN, 1). Herein we report the development of an efficient enantioselective synthesis of the two isomers, R-DPN (3) and S-DPN (2), and we have compared the in vitro ligand binding affinities, coactivator binding affinities and recruitment potencies, and cellular transcriptional potencies of these isomers. Both enantiomers show a very high affinity and potency preference for ERβ over ERα, typically in the range of 80-300 fold. Although the enantioselectivity is only modest (3-4 fold), the R-enantiomer is the higher affinity and more potent isomer. While ERβ can be effectively and selectively stimulated by rac-DPN or by either R-DPN or S-DPN, R-DPN might be the preferred member of this isomeric series for biological studies of ERβ function. PMID:22122563

  16. Diarylpropionitrile (DPN) enantiomers: synthesis and evaluation of estrogen receptor β-selective ligands.

    PubMed

    Carroll, Vincent M; Jeyakumar, M; Carlson, Kathryn E; Katzenellenbogen, John A

    2012-01-12

    Two estrogen receptor (ER) subtypes, ERα and ERβ, mediate the actions of estrogens in diverse reproductive and nonreproductive target tissues. ER subtype-selective ligands, which bind to and activate these subtypes differentially, have proved to be useful in elucidating which actions of estrogens proceed through ERα vs ERβ. Some of these ligands show potential as novel therapeutic agents. Diarylpropionitrile (DPN), an ERβ selective ligand that we developed, is a chiral molecule, but it has been studied almost exclusively as the racemic mixture (rac-DPN, 1). Herein we report the development of an efficient enantioselective synthesis of the two isomers, R-DPN (3) and S-DPN (2), and we have compared the in vitro ligand binding affinities, coactivator binding affinities, recruitment potencies, and cellular transcriptional potencies of these isomers. Both enantiomers show a very high affinity and potency preference for ERβ over ERα, typically in the range of 80-300-fold. Although the enantioselectivity is only modest (3-4-fold), the R-enantiomer is the higher affinity and more potent isomer. While ERβ can be effectively and selectively stimulated by rac-DPN or by either R-DPN or S-DPN, R-DPN might be the preferred member of this isomeric series for biological studies of ERβ function.

  17. Use of vancomycin silica stationary phase in packed capillary electrochromatography I. Enantiomer separation of basic compounds.

    PubMed

    Desiderio, C; Aturki, Z; Fanali, S

    2001-02-01

    Chiral separation of basic compounds was achieved by using 75 or 100 microm ID fused-silica capillaries packed with a vanoomycin-modified diol silica stationary phase. The capillary was firstly packed for about 12 cm with a slurry mixture composed of diolsilica (3:1) then with the vancomycin modified diol-silica (3:1) (23 cm), and finally with diol-silica (3:1) for about 2 cm. Frits were prepared by a heating wire at the two ends of the capillary; the detector window was prepared at 8.5 cm from the end of the capillary where vancomycin was not present. The influence of the mobile phase composition (pH and concentration, organic modifier type and concentration) on the velocity of the electroosmotic flow, chiral resolution and enantioselectivity was studied. Good enantiomeric resolution was achieved for atenolol, oxprenolol, propranolol, and venlafaxine using a mobile phase composition of 100 mM ammonium acetate solution (pH 6)/water/acetonitrile (5:5:90 v/v/v) while for terbutaline a mixture of 5:15:80 v/v/v provided the best separations. The use of methanol instead of acetonitrile caused a general increase of enantiomer resolution of the studied compounds together with a reduction of efficiency and detector response. However, the combination of acetonitrile and methanol in the mobile phase (as, e.g., 10% methanol and 80% acetonitrile) allowed to improve the enantiomer resolution with satisfactory detector response.

  18. Highly selective separation of enantiomers using a chiral porous organic cage.

    PubMed

    Zhang, Jun-Hui; Xie, Sheng-Ming; Wang, Bang-Jin; He, Pin-Gang; Yuan, Li-Ming

    2015-12-24

    Porous solids composed of shape-persistent organic cage molecules have attracted considerable attention due to their important applications such as molecular separation, heterogeneous catalysis, and gas storage. In this study, an imine-linked porous organic cage (POC) CC10 diluted with a polysiloxane OV-1701 was explored as a novel stationary phase for high-resolution gas chromatography (GC). A wide variety of enantiomers belonging to different classes of organic compounds have been resolved on the coated capillary column, including chiral alcohols, esters, ketones, ethers, halohydrocarbons, epoxides, and organic acids. The fabricated column complements to commercial β-DEX 120 column and our recently reported CC3-R column for separating enantiomers, which indicates that the excellent chiral recognition ability of CC10 is not only interesting academically, but also has potential for practical application. In addition, CC10 also exhibits good selectivity for the separation of n-alkanes, n-alcohols, Grob mixture, and positional isomers. This work also indicates that this type of chiral POCs will become a new class of chiral selector in the near future. PMID:26632517

  19. Selective preparation of enantiomers by laser pulses: From optimal control to specific pump and dump transitions

    NASA Astrophysics Data System (ADS)

    González, L.; Hoki, K.; Kröner, D.; Leal, A. S.; Manz, J.; Ohtsuki, Y.

    2000-12-01

    Starting from optimal control, various series of infrared, ultrashort laser pulses with analytical shapes are designed in order to drive a preoriented molecule from its ground torsional state, which represents the coherent superposition of left and right atropisomers, towards a single enantiomer. Close analysis of the population dynamics, together with the underlying symmetry selection rules for the laser induced transitions, yields the mechanism. Namely, the molecule is driven from its ground vibrational state towards the coherent superposition of the lowest doublet of states via a doublet of excited torsional states with opposite symmetries. This pump-and-dump mechanism can be achieved by simpler series of analytical laser pulses. This decomposition of the optimal pulse into analytical subpulses allows us to design different scenarios for the selective preparation of left or right enantiomers. Exemplary this is demonstrated by quantum simulations of representative wave packets for the torsional motions of the model system, H2POSH, in the electronic ground state, based on the ab initio potential energy surface, and with ab initio dipole couplings.

  20. Enantiomer discrimination illustrated by the high resolution crystal structures of type 4 phosphodiesterase.

    PubMed

    Huai, Qing; Sun, Yingjie; Wang, Huanchen; Macdonald, Dwight; Aspiotis, Renée; Robinson, Howard; Huang, Zheng; Ke, Hengming

    2006-03-23

    Type 4 phosphodiesterase (PDE4) inhibitors are emerging as new treatments for a number of disorders including asthma and chronic obstructive pulmonary disease. Here we report the biochemical characterization on the second generation inhibitor (+)-1 (L-, IC50=0.4 nM) and its enantiomer (-)-1 (L-, IC50=43 nM) and their cocrystal structures with PDE4D at 2.0 A resolution. Despite the 107-fold affinity difference, both enantiomers interact with the same sets of residues in the rigid active site. The weaker (-)-1 adopts an unfavorable conformation to preserve the pivotal interactions between the Mg-bound waters and the N-oxide of pyridine. These structures support a model in which inhibitors are anchored by the invariant glutamine at one end and the metal-pocket residues at another end. This model provides explanations for most of the observed structure-activity relationship and the metal ion dependency of the catechol-ether based inhibitors and should facilitate their further design.

  1. Albendazole in environment: faecal concentrations in lambs and impact on lower development stages of helminths and seed germination.

    PubMed

    Prchal, Lukáš; Podlipná, Radka; Lamka, Jiří; Dědková, Tereza; Skálová, Lenka; Vokřál, Ivan; Lecová, Lenka; Vaněk, Tomáš; Szotáková, Barbora

    2016-07-01

    Albendazole (ABZ), widely used benzimidazole anthelmintic, administered to animals enters via excrements into environment and may impact non-target organisms. Moreover, exposure of lower development stages of helminths to anthelmintics may also encourage the development of drug-resistant strains of helminths. In present project, the kinetics of ABZ (10 mg kg(-1) p.o.) and its metabolite (ABZ.SO, ABZSO2) elimination in faeces from treated Texel lambs were studied using UHPLC/MS/MS with the aim to find out their concentrations achievable in the environment. Consequently, the effect of these compounds on lower development stages of Barber's pole worm (Haemonchus contortus) and on germination of white mustard (Sinapis alba) seeds was evaluated. The results showed that ABZ concentrations in faeces excreted in 4-60 h after treatment were above the concentrations lethal for H. contortus eggs. Moreover, pre-incubation with sub-lethal doses of ABZ and ABZ.SO did not increase the resistance of H. contortus eggs and larvae to anthelmintics. On the other hand, concentrations of ABZ and ABZ.SO in faeces are so high that might have negative influence on non-target soil invertebrates. As neither ABZ nor its metabolites affect the germination of mustard seeds, phytoremediation could be considered as potential tool for detoxification of ABZ in the environment. PMID:26996913

  2. Cystic echinococcosis therapy: Albendazole-loaded lipid nanocapsules enhance the oral bioavailability and efficacy in experimentally infected mice.

    PubMed

    Pensel, Patricia E; Ullio Gamboa, Gabriela; Fabbri, Julia; Ceballos, Laura; Sanchez Bruni, Sergio; Alvarez, Luis I; Allemandi, Daniel; Benoit, Jean Pierre; Palma, Santiago D; Elissondo, María C

    2015-12-01

    Therapeutic failures attributed to medical management of cystic echinococcosis (CE) with albendazole (ABZ) have been primarily linked to the poor drug absorption rate resulting in low drug level in plasma and hydatid cysts. Lipid nanocapsules (LNCs) represent nanocarriers designed to encapsulate lipophilic drugs, such as ABZ. The goals of the current work were: (i) to characterize the plasma and cyst drug exposure after the administration of ABZ as ABZ-LNCs or ABZ suspension (ABZ-SUSP) in mice infected with Echinococcus granulosus, and ii) to compare the clinical efficacies of both ABZ formulations. Enhanced ABZ sulphoxide (ABZ-SO) concentration profiles were obtained in plasma and cysts from ABZ-LNC treated animals. ABZSO exposure (AUC0-LOQ) was significantly higher in plasma and cyst after the ABZ-LNC treatments, both orally and subcutaneously, compared to that observed after oral administration of ABZ-SUSP. Additionally, ABZSO concentrations measured in cysts from ABZ-LNC treated mice were 1.7-fold higher than those detected in plasma. This enhanced drug availability correlated with an increased efficacy against secondary CE in mice observed for the ABZ-LNCs, while ABZ-SUSP did not reach differences with the untreated control group. This new pharmacotechnically-based strategy could be a potential alternative to improve the treatment of human CE. PMID:26409727

  3. Efficacy of different albendazole and mebendazole regimens against heavy-intensity Trichuris trichiura infections in school children, Jimma Town, Ethiopia.

    PubMed

    Mekonnen, Z; Levecke, B; Boulet, G; Bogers, J-P; Vercruysse, J

    2013-06-01

    Recent studies have shown that the efficacy of benzimidazole drugs is influenced by the intensity of trichuriasis. Therefore, the objective of this study was to determine the efficacy of albendazole (ALB) and mebendazole (MBZ) administered randomly for 1 (ALB×1 and MBZ×1) or 2 days (ALB×2 and MBZ×2) to 385 school children with heavy-intensity trichuriasis (mean faecal egg counts (FEC) >1000 eggs per gram of stool (epg)) in Jimma Town, Ethiopia. The efficacies (95% confidence intervals) by means of reduction in faecal egg counts (FECs) were 29·3% (-9·9-56·2), 60·0% (48·5-70·9), 73·5% (64·2-81·3), and 87·1% (81·4-91·2) for ALB×1, MBZ×1, ALB×2, and MBZ×2, respectively. These observations highlight that assessment of the anthelmintic efficacy of existing or new compounds against Trichuris trichiura should be assessed under varying levels of infection intensity.

  4. Biotransformation of albendazole and activities of selected detoxification enzymes in Haemonchus contortus strains susceptible and resistant to anthelmintics.

    PubMed

    Vokřál, Ivan; Jirásko, Robert; Stuchlíková, Lucie; Bártíková, Hana; Szotáková, Barbora; Lamka, Jiří; Várady, Marián; Skálová, Lenka

    2013-09-23

    The increased activity of drug-metabolizing enzymes can protect helminths against the toxic effect of anthelmintics. The aim of this study was to compare the metabolism of the anthelmintic drug albendazole (ABZ) and the activities of selected biotransformation and antioxidant enzymes in three different strains of Haemonchus contortus: the ISE strain (susceptible to common anthelmintics), the BR strain (resistant to benzimidazole anthelmintics) and the WR strain (multi-resistant). H. contortus adults were collected from the abomasum of experimentally infected lambs. In vitro (subcellular fractions of H. contortus homogenate) as well as ex vivo (living nematodes cultivated in flasks with medium) experiments were performed. HPLC with spectrofluorimetric and mass-spectrometric detection was used in the analysis of ABZ metabolites. The in vitro activities of oxidation/antioxidation and conjugation enzymes toward model substrates were also assayed. The in vitro data showed significant differences between the susceptible (ISE) and resistant (BR, WR) strains regarding the activities of peroxidases, catalase and UDP-glucosyltransferases. S-oxidation of ABZ was significantly lower in BR than in the ISE strain. Ex vivo, four ABZ metabolites were identified: ABZ sulphoxide and three ABZ glucosides. In the resistant strains BR and WR, the ex vivo formation of all ABZ glucosides was significantly higher than in the susceptible ISE strain. The altered activities of certain detoxifying enzymes might partly protect the parasites against the toxic effect of the drugs as well as contribute to drug-resistance in these parasites.

  5. Albendazole in environment: faecal concentrations in lambs and impact on lower development stages of helminths and seed germination.

    PubMed

    Prchal, Lukáš; Podlipná, Radka; Lamka, Jiří; Dědková, Tereza; Skálová, Lenka; Vokřál, Ivan; Lecová, Lenka; Vaněk, Tomáš; Szotáková, Barbora

    2016-07-01

    Albendazole (ABZ), widely used benzimidazole anthelmintic, administered to animals enters via excrements into environment and may impact non-target organisms. Moreover, exposure of lower development stages of helminths to anthelmintics may also encourage the development of drug-resistant strains of helminths. In present project, the kinetics of ABZ (10 mg kg(-1) p.o.) and its metabolite (ABZ.SO, ABZSO2) elimination in faeces from treated Texel lambs were studied using UHPLC/MS/MS with the aim to find out their concentrations achievable in the environment. Consequently, the effect of these compounds on lower development stages of Barber's pole worm (Haemonchus contortus) and on germination of white mustard (Sinapis alba) seeds was evaluated. The results showed that ABZ concentrations in faeces excreted in 4-60 h after treatment were above the concentrations lethal for H. contortus eggs. Moreover, pre-incubation with sub-lethal doses of ABZ and ABZ.SO did not increase the resistance of H. contortus eggs and larvae to anthelmintics. On the other hand, concentrations of ABZ and ABZ.SO in faeces are so high that might have negative influence on non-target soil invertebrates. As neither ABZ nor its metabolites affect the germination of mustard seeds, phytoremediation could be considered as potential tool for detoxification of ABZ in the environment.

  6. A mathematical model for long-term effect of diethylcarbamazine-albendazole mass drug administration on lymphatic filariasis

    NASA Astrophysics Data System (ADS)

    Tasman, H.; Supali, T.; Supriatna, A. K.; Nuraini, N.; Soewono, E.

    2015-03-01

    In this paper we discuss a mathematical model for the transmission of lymphatic filariasis disease. The human population is divided into susceptible, latent, acute and chronic subpopulations. Treatment is carried out within the scheme of mass drug administration (MDA) by giving the diethylcarbamazine (DEC) and albendazole (ALB) to all individuals. In the model, we assume that the treatments have direct killing effect to microfilariae, increase of immune-mediated effect. The treated individuals are assumed to remain susceptible to the disease. This is due to the fact that the treatment is only partially effective against macrofilaria. Simulations of the model reveals that DEC-ALB treatment does give significant reduction of acute and chronic compartments at the end of the treatment period and slow down the growth after the treatment before eventually tend to the endemic state. It showed that repeated treatment during MDA is effective to decrease the transmission. This suggests that terminating MDA program after a long period of its application may still effective in controlling the disease.

  7. Theoretical Modeling of the Chirality Discrimination of Enantiomers by Nanotubular Cyclic Peptides using Gas-Phase Photoelectron Spectroscopy: An ONIOM Spectroscopic Calculations.

    PubMed

    Farrokhpour, H; Karachi, S; Chermahini, A Najafi

    2016-09-01

    In the present work, the chirality recognition of the enantiomers of a chiral molecule (1-phenyl-1-propanol) interacting with a nanotubular cyclic peptide (E-type cyclic decapeptide) was investigated by their ionization in the gas phase, theoretically. The absolute energy difference between the interaction of the S- and R-enantiomer with the cyclic peptide, calculated at the M06-2X/6-311++G(d, p) level of theory, was 4.70 kcal·mol(-1). Two different schemes of "Our own N-layered Integrated molecular Orbital and molecular Mechanics (ONIOM)" method such as (quantum mechanics (QM):molecular mechanics (MM)) and (QM:QM) were employed to study the effect of the interaction on the gas-phase ionization energies of the enantiomers and cyclic peptide, separately. The symmetry-adapted cluster/configuration interaction (SAC-CI) methodology was used for the calculation of the ionization energies. It was found that the difference between the interactions of R- and S-enantiomer with the cyclic peptide caused different changes in the photoelectron spectrum of each enantiomer so that these changes could be used for the chirality discrimination of the enantiomers in the gas phase. Similarly, the photoelectron spectrum of the cyclic peptide interacting with the R and S-enantiomer were calculated, separately, and it was observed that the difference in the interaction with the R- and S-enantiomer created different changes in the spectrum of cyclic peptide. Finally, it was shown that the difference in the interaction of cyclic peptide with the enantiomers of a chiral molecule in the gas phase can be used for the identification of enantiomers in the gas phase by the direct ionization. PMID:27500312

  8. Methionine sulfoxide reductase A regulates cell growth through the p53-p21 pathway

    SciTech Connect

    Choi, Seung Hee; Kim, Hwa-Young

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer Down-regulation of MsrA inhibits normal cell proliferation. Black-Right-Pointing-Pointer MsrA deficiency leads to an increase in p21 by enhanced p53 acetylation. Black-Right-Pointing-Pointer Down-regulation of MsrA causes cell cycle arrest at the G{sub 2}/M stage. Black-Right-Pointing-Pointer MsrA is a regulator of cell growth that mediates the p53-p21 pathway. -- Abstract: MsrA is an oxidoreductase that catalyzes the stereospecific reduction of methionine-S-sulfoxide to methionine. Although MsrA is well-characterized as an antioxidant and has been implicated in the aging process and cellular senescence, its roles in cell proliferation are poorly understood. Here, we report a critical role of MsrA in normal cell proliferation and describe the regulation mechanism of cell growth by this protein. Down-regulation of MsrA inhibited cell proliferation, but MsrA overexpression did not promote it. MsrA deficiency led to an increase in p21, a major cyclin-dependent kinase inhibitor, thereby causing cell cycle arrest at the G{sub 2}/M stage. While protein levels of p53 were not altered upon MsrA deficiency, its acetylation level was significantly elevated, which subsequently activated p21 transcription. The data suggest that MsrA is a regulator of cell growth that mediates the p53-p21 pathway.

  9. Extracellular respiration of dimethyl sulfoxide by Shewanella oneidensis strain MR-1.

    PubMed

    Gralnick, Jeffrey A; Vali, Hojatollah; Lies, Douglas P; Newman, Dianne K

    2006-03-21

    Shewanella species are renowned for their respiratory versatility, including their ability to respire poorly soluble substrates by using enzymatic machinery that is localized to the outside of the cell. The ability to engage in "extracellular respiration" to date has focused primarily on respiration of minerals. Here, we identify two gene clusters in Shewanella oneidensis strain MR-1 that each contain homologs of genes required for metal reduction and genes that are predicted to encode dimethyl sulfoxide (DMSO) reductase subunits. Molecular and genetic analyses of these clusters indicate that one (SO1427-SO1432) is required for anaerobic respiration of DMSO. We show that DMSO respiration is an extracellular respiratory process through the analysis of mutants defective in type II secretion, which is required for transporting proteins to the outer membrane in Shewanella. Moreover, immunogold labeling of DMSO reductase subunits reveals that they reside on the outer leaflet of the outer membrane under anaerobic conditions. The extracellular localization of the DMSO reductase in S. oneidensis suggests these organisms may perceive DMSO in the environment as an insoluble compound.

  10. Dimethyl sulfoxide modulates NF-kappa B and cytokine activation in lipopolysaccharide-treated murine macrophages.

    PubMed Central

    Kelly, K A; Hill, M R; Youkhana, K; Wanker, F; Gimble, J M

    1994-01-01

    Antioxidants are protective against septic shock in animal models. Recently, free radical scavengers have been found to inhibit the activation of the NF-kappa B protein in a number of cell lines. This transcriptional regulatory protein binds to the promoters of the proinflammatory cytokines tumor necrosis factor, interleukin-6, and the macrophage inflammatory proteins. The current work examined lipopolysaccharide-induced NF-kappa B activation in the J774 macrophage-like cell line and primary peritoneal macrophages from lipopolysaccharide-responsive (C3HeB/Fej) and -nonresponsive (C3H/HeJ) murine strains. The DNA-binding activity of the NF-kappa B protein directly correlated with mRNA expression for the genes encoding the proinflammatory cytokines and the free radical scavenging enzyme, superoxide dismutase. Both the p50 and p65 NF-kappa B subunits were detected on gel supershift assays. Minimal NF-kappa B activity was observed following exposure of C3H/HeJ macrophages to lipopolysaccharide. The antioxidant dimethyl sulfoxide decreased the level of NF-kappa B activation in the J774 cells. This correlated with decreased expression of cytokine mRNAs and tumor necrosis factor bioactivity. These results suggest that modulation of NF-kappa B activation may provide a mechanism through which antioxidants protect against endotoxemia in murine models. Images PMID:8039880

  11. Solvent stimulated actuation of polyurethane-based shape memory polymer foams using dimethyl sulfoxide and ethanol

    NASA Astrophysics Data System (ADS)

    Boyle, A. J.; Weems, A. C.; Hasan, S. M.; Nash, L. D.; Monroe, M. B. B.; Maitland, D. J.

    2016-07-01

    Solvent exposure has been investigated to trigger actuation of shape memory polymers (SMPs) as an alternative to direct heating. This study aimed to investigate the feasibility of using dimethyl sulfoxide (DMSO) and ethanol (EtOH) to stimulate polyurethane-based SMP foam actuation and the required solvent concentrations in water for rapid actuation of hydrophobic SMP foams. SMP foams exhibited decreased T g when submerged in DMSO and EtOH when compared to water submersion. Kinetic DMA experiments showed minimal or no relaxation for all SMP foams in water within 30 min, while SMP foams submerged in EtOH exhibited rapid relaxation within 1 min of submersion. SMP foams expanded rapidly in high concentrations of DMSO and EtOH solutions, where complete recovery over 30 min was observed in DMSO concentrations greater than 90% and in EtOH concentrations greater than 20%. This study demonstrates that both DMSO and EtOH are effective at triggering volume recovery of polyurethane-based SMP foams, including in aqueous environments, and provides promise for use of this actuation technique in various applications.

  12. Multinuclear NMR spectroscopy for differentiation of molecular configurations and solvent properties between acetone and dimethyl sulfoxide

    NASA Astrophysics Data System (ADS)

    Wen, Yuan-Chun; Kuo, Hsiao-Ching; Jia, Hsi-Wei

    2016-04-01

    The differences in molecular configuration and solvent properties between acetone and dimethyl sulfoxide (DMSO) were investigated using the developed technique of 1H, 13C, 17O, and 1H self-diffusion liquid state nuclear magnetic resonance (NMR) spectroscopy. Acetone and DMSO samples in the forms of pure solution, ionic salt-added solution were used to deduce their active sites, relative dipole moments, dielectric constants, and charge separations. The NMR results suggest that acetone is a trigonal planar molecule with a polarized carbonyl double bond, whereas DMSO is a trigonal pyramidal-like molecule with a highly polarized S-O single bond. Both molecules use their oxygen atoms as the active sites to interact other molecules. These different molecular models explain the differences their physical and chemical properties between the two molecules and explain why DMSO is classified as an aprotic but highly dipolar solvent. The results are also in agreement with data obtained using X-ray diffraction, neutron diffraction, and theoretical calculations.

  13. Aggregation behavior of N-alkyl perfluorooctanesulfonamides in dimethyl sulfoxide solution.

    PubMed

    Li, Guo-Li; Gao, Yan-An; Li, Xin-Wei; Liu, Jie; Zheng, Li-Qiang; Xing, Hang; Xiao, Jin-Xin

    2010-02-15

    N-alkyl perfluorooctanesulfonamides (C8F17SO2NHCnH2n+1, FC8-HCn, n = 2, 4, 6, 8) were shown to form aggregates in dimethyl sulfoxide (DMSO). Surface tension results revealed that the dissolution of FC8-HCn reduced the surface tension of DMSO in a manner analogous to common surfactants in aqueous solutions. Maximum surface excess amount (Gamma(max)) and minimum surface area per molecule (Amin) at the air-liquid interface were estimated. Gamma(max) decreases and Amin increases with an increase of the hydrocarbon chain length of FC8-HCn. Steady-state fluorescence and NMR measurements demonstrated that both fluorocarbon and hydrocarbon chains of FC8-HCn molecules were incorporated inside the aggregates. UV-vis spectroscopy confirmed the formation of aggregates and determined the critical micelle concentration (cmc) of FC8-HC6 and FC8-HC8 solutions. The thermodynamic parameters DeltaG(0)(agg), DeltaH(0)(agg), and DeltaS(0)(agg) for the aggregate formation of FC8-HCn in DMSO derived from the temperature dependence of the cmc revealed that the aggregate formation is an enthalpy-driven process, which was further confirmed by isothermal titration calorimetry (ITC) measurements. Moreover, the absolute values of DeltaG(0)(agg) and DeltaH(0)(agg) increase with an increase of the hydrocarbon chain length of FC8-HCn at 298 K.

  14. A catalase-peroxidase for oxidation of β-lactams to their (R)-sulfoxides.

    PubMed

    Sangar, Shefali; Pal, Mohan; Moon, Lomary S; Jolly, Ravinder S

    2012-07-01

    In this communication we report for the first time a biocatalytic method for stereoselective oxidation of β-lactams, represented by penicillin-G, penicillin-V and cephalosporin-G to their (R)-sulfoxides. The method involves use of a bacterium, identified as Bacillus pumilis as biocatalyst. The enzyme responsible for oxidase activity has been purified and characterized as catalase-peroxidase (KatG). KatG of B. pumilis is a heme containing protein showing characteristic heme spectra with soret peak at 406 nm and visible peaks at 503 and 635 nm. The major properties that distinguish B. pumilis KatG from other bacterial KatGs are (i) it is a monomer and contains one heme per monomer, whereas KatGs of other bacteria are dimers or tetramers and have low heme content of about one per dimer or two per tetramer and (ii) its 12-residue, N-terminal sequence obtained by Edman degradation did not show significant similarity with any of known KatGs. PMID:21996477

  15. Structural, energetic, and electronic properties of La(III)-dimethyl sulfoxide clusters.

    PubMed

    Bodo, Enrico; Chiricotto, Mara; Spezia, Riccardo

    2014-12-11

    By using accurate density functional theory calculations, we have studied the cluster complexes of a La(3+) ion interacting with a small number of dimethyl sulfoxide (DMSO) molecules of growing size (from 1 to 12). Extended structural, energetic, and electronic structure analyses have been performed to provide a complete picture of the physical properties that are the basis of the interaction of La(III) with DMSO. Recent experimental data in the solid and liquid phase have suggested a coordination number of 8 DMSO molecules with a square antiprism geometry arranged similarly in the liquid and crystalline phases. By using a cluster approach on the La(3+)(DMSO)n gas phase isolated structures, we have found that the 8-fold geometry, albeit less regular than in the crystal, is probably the most stable cluster. Furthermore, we provide new evidence of a 9-fold complexation geometric arrangement that is competitive (at least energetically) with the 8-fold one and that might suggest the existence of transient structures with higher coordination numbers in the liquid phase.

  16. Dimethyl sulfoxide induces chemotherapeutic resistance in the treatment of testicular embryonal carcinomas

    PubMed Central

    KITA, HIROKO; OKAMOTO, KEISEI; KUSHIMA, RYOJI; KAWAUCHI, AKIHIRO; CHANO, TOKUHIRO

    2015-01-01

    Dimethyl sulfoxide (DMSO) is an amphipathic molecule that is used as a solvent in biological studies and as a vehicle for drug therapy. The present study was designed to evaluate the potential effects of DMSO as a solvent in the treatment of testicular embryonal carcinomas (ECs). DMSO was applied to two human EC cell lines (NEC8 and NEC14), with the treated cells evaluated in relation to cisplatin (CDDP) resistance, differentiation (using Vimentin, Fibronectin, TRA-1-60, and SSEA-1 and -3 as markers) and stemness (denoted by expression of SOX2 and OCT3/4). Furthermore, DNA methyltransferase (DNMT-1, -3A and -3L) expression and methylation status were analyzed. DMSO induced resistance to CDDP, aberrant differentiation and reduction of stemness-related markers in each of the EC cell lines. The expression levels of DNMT-3L and -3A were reduced in response to DMSO, while this treatment also affected DNA methylation. The data demonstrated that DMSO perturbed differentiation, reduced stemness and induced resistance to CDDP in human EC cells. Therefore, DMSO could reduce drug efficacy against EC cells and its use should be carefully managed in the clinical application of chemotherapy. PMID:26622550

  17. Effect of interferon on dimethyl sulfoxide-stimulated Friend erythroleukemic cells: ultrastructural and biochemical study.

    PubMed Central

    Luftig, R B; Conscience, J F; Skoultchi, A; McMillan, P; Revel, M; Ruddle, F H

    1977-01-01

    Treatment of dimethyl sulfoxide-stimulated Friend erythroleukemic cells (clone 745) with mouse interferon (50 U/ml) led to the following changes: (i) a net decrease (40 to 60%) in both the total number of apparently newly synthesized virion particles per cell section and in the average number of cell sections containing one or more virion particles; (ii) a large decrease (80 to 90%) in the number of particles released into the supernatant fluid, as assayed by reverse transcriptase activity; (iii) an initial increase in the number of "immature" or "enveloped A-type" virions followed by an increase in the accumulation of empty, core shell-like particles; and (iv) a decrease in the number of cytoplasmic vacuolar structures, which have been implicated as a major site of virus production and which we show here by serial sectioning to be, in several instances, invaginations of the plasma membrane. The effects on virus production were noticeable 2 h after interferon addition and reached their full extent by 13 h. We conclude from these observations that interferon acts upon the late stage(s) of virion maturation, leading both to a decrease in virion production as well as to the formation of defective particles. In contrast, a small but significant increase in the rate at which globin mRNA and hemoglobin accumulate is observed after interferon treatment. Images PMID:561195

  18. Dimethyl sulfoxide at high concentrations inhibits non-selective cation channels in human erythrocytes.

    PubMed

    Nardid, Oleg A; Schetinskey, Miroslav I; Kucherenko, Yuliya V

    2013-03-01

    Dimethyl sulfoxide (DMSO), a by-product of the pulping industry, is widely used in biological research, cryobiology and medicine. On cellular level DMSO was shown to suppress NMDA-AMPA channels activation, blocks Na+ channel activation and attenuates Ca2+ influx (Lu and Mattson 2001). In the present study we explored the whole-cell patch-clamp to examine the acute effect of high concentrations of DMSO (0.1-2 mol/l) on cation channels activity in human erythrocytes. Acute application of DMSO (0.1-2 mol/l) dissolved in Cl--containing saline buffer solution significantly inhibited cation conductance in human erythrocytes. Inhibition was concentration-dependent and had an exponential decay profile. DMSO (2 mol/l) induced cation inhibition in Cl-- containing saline solutions of: 40.3 ± 3.9% for K+, 35.4 ± 3.1% for Ca2+ and 47.4 ± 1.9% for NMDG+. Substitution of Cl- with gluconate- increased the inhibitory effect of DMSO on the Na+ current. Inhibitory effect of DMSO was neither due to high permeability of erythrocytes to DMSO nor to an increased tonicity of the bath media since no effect was observed in 2 mol/l glycerol solution. In conclusion, we have shown that high concentrations of DMSO inhibit the non-selective cation channels in human erythrocytes and thus protect the cells against Na+ and Ca2+ overload. Possible mechanisms of DMSO effect on cation conductance are discussed. PMID:23531832

  19. Arabidopsis Peptide Methionine Sulfoxide Reductase2 Prevents Cellular Oxidative Damage in Long NightsW⃞

    PubMed Central

    Bechtold, Ulrike; Murphy, Denis J.; Mullineaux, Philip M.

    2004-01-01

    Peptide methionine sulfoxide reductase (PMSR) is a ubiquitous enzyme that repairs oxidatively damaged proteins. In Arabidopsis (Arabidopsis thaliana), a null mutation in PMSR2 (pmsr2-1), encoding a cytosolic isoform of the enzyme, exhibited reduced growth in short-day conditions. In wild-type plants, a diurnally regulated peak of total PMSR activity occurred at the end of the 16-h dark period that was absent in pmsr2-1 plants. This PMSR activity peak in the wild-type plant coincided with increased oxidative stress late in the dark period in the mutant. In pmsr2-1, the inability to repair proteins resulted in higher levels of their turnover, which in turn placed an increased burden on cellular metabolism. This caused increased respiration rates, leading to the observed higher levels of oxidative stress. In wild-type plants, the repair of damaged proteins by PMSR2 at the end of the night in a short-day diurnal cycle alleviates this potential burden on metabolism. Although PMSR2 is not absolutely required for viability of plants, the observation of increased damage to proteins in these long nights suggests the timing of expression of PMSR2 is an important adaptation for conservation of their resources. PMID:15031406

  20. Comparative study of halogen- and hydrogen-bond interactions between benzene derivatives and dimethyl sulfoxide.

    PubMed

    Zheng, Yan-Zhen; Deng, Geng; Zhou, Yu; Sun, Hai-Yuan; Yu, Zhi-Wu

    2015-08-24

    The halogen bond, similar to the hydrogen bond, is an important noncovalent interaction and plays important roles in diverse chemistry-related fields. Herein, bromine- and iodine-based halogen-bonding interactions between two benzene derivatives (C6 F5 Br and C6 F5 I) and dimethyl sulfoxide (DMSO) are investigated by using IR and NMR spectroscopy and ab initio calculations. The results are compared with those of interactions between C6 F5 Cl/C6 F5 H and DMSO. First, the interaction energy of the hydrogen bond is stronger than those of bromine- and chlorine-based halogen bonds, but weaker than iodine-based halogen bond. Second, attractive energies depend on 1/r(n) , in which n is between three and four for both hydrogen and halogen bonds, whereas all repulsive energies are found to depend on 1/r(8.5) . Third, the directionality of halogen bonds is greater than that of the hydrogen bond. The bromine- and iodine-based halogen bonds are strict in this regard and the chlorine-based halogen bond only slightly deviates from 180°. The directional order is iodine-based halogen bond>bromine-based halogen bond>chlorine-based halogen bond>hydrogen bond. Fourth, upon the formation of hydrogen and halogen bonds, charge transfers from DMSO to the hydrogen- and halogen-bond donors. The CH3 group contributes positively to stabilization of the complexes.

  1. Marmoset induced pluripotent stem cells: Robust neural differentiation following pretreatment with dimethyl sulfoxide.

    PubMed

    Qiu, Zhifang; Mishra, Anuja; Li, Miao; Farnsworth, Steven L; Guerra, Bernadette; Lanford, Robert E; Hornsby, Peter J

    2015-07-01

    The marmoset is an important nonhuman primate model for regenerative medicine. For experimental autologous cell therapy based on induced pluripotent (iPS) cells in the marmoset, cells must be able to undergo robust and reliable directed differentiation that will not require customization for each specific iPS cell clone. When marmoset iPS cells were aggregated in a hanging drop format for 3 days, followed by exposure to dual SMAD inhibitors and retinoic acid in monolayer culture for 3 days, we found substantial variability in the response of different iPS cell clones. However, when clones were pretreated with 0.05-2% dimethyl sulfoxide (DMSO) for 24 hours, all clones showed a very similar maximal response to the directed differentiation scheme. Peak responses were observed at 0.5% DMSO in two clones and at 1% DMSO in a third clone. When patterns of gene expression were examined by microarray analysis, hierarchical clustering showed very similar responses in all 3 clones when they were pretreated with optimal DMSO concentrations. The change in phenotype following exposure to DMSO and the 6 day hanging drop/monolayer treatment was confirmed by immunocytochemistry. Analysis of DNA content in DMSO-exposed cells indicated that it is unlikely that DMSO acts by causing cells to exit from the cell cycle. This approach should be generally valuable in the directed neural differentiation of pluripotent cells for experimental cell therapy. PMID:26070112

  2. Ion transport properties of magnesium bromide/dimethyl sulfoxide non-aqueous liquid electrolyte

    PubMed Central

    Sheha, E.

    2015-01-01

    Nonaqueous liquid electrolyte system based dimethyl sulfoxide DMSO and magnesium bromide (MgBr2) is synthesized via ‘Solvent-in-Salt’ method for the application in magnesium battery. Optimized composition of MgBr2/DMSO electrolyte exhibits high ionic conductivity of 10−2 S/cm at ambient temperature. This study discusses different concentrations from 0 to 5.4 M of magnesium salt, representing low, intermediate and high concentrations of magnesium salt which are examined in frequency dependence conductivity studies. The temperature dependent conductivity measurements have also been carried out to compute activation energy (Ea) by least square linear fitting of Arrhenius plot: ‘log σ − 1/T. The transport number of Mg2+ ion determined by means of a combination of d.c. and a.c. techniques is ∼0.7. A prototype cell was constructed using nonaqueous liquid electrolyte with Mg anode and graphite cathode. The Mg/graphite cell shows promising cycling. PMID:26843967

  3. Solvation structure and transport properties of alkali cations in dimethyl sulfoxide under exogenous static electric fields

    SciTech Connect

    Kerisit, Sebastien; Vijayakumar, M. E-mail: karl.mueller@pnnl.gov; Han, Kee Sung; Mueller, Karl T. E-mail: karl.mueller@pnnl.gov

    2015-06-14

    A combination of molecular dynamics simulations and pulsed field gradient nuclear magnetic resonance spectroscopy is used to investigate the role of exogenous electric fields on the solvation structure and dynamics of alkali ions in dimethyl sulfoxide (DMSO) and as a function of temperature. Good agreement was obtained, for select alkali ions in the absence of an electric field, between calculated and experimentally determined diffusion coefficients normalized to that of pure DMSO. Our results indicate that temperatures of up to 400 K and external electric fields of up to 1 V nm{sup −1} have minimal effects on the solvation structure of the smaller alkali cations (Li{sup +} and Na{sup +}) due to their relatively strong ion-solvent interactions, whereas the solvation structures of the larger alkali cations (K{sup +}, Rb{sup +}, and Cs{sup +}) are significantly affected. In addition, although the DMSO exchange dynamics in the first solvation shell differ markedly for the two groups, the drift velocities and mobilities are not significantly affected by the nature of the alkali ion. Overall, although exogenous electric fields induce a drift displacement, their presence does not significantly affect the random diffusive displacement of the alkali ions in DMSO. System temperature is found to have generally a stronger influence on dynamical properties, such as the DMSO exchange dynamics and the ion mobilities, than the presence of electric fields.

  4. [Permeability of isolated rat hepatocyte plasma membranes for molecules of dimethyl sulfoxide].

    PubMed

    Kuleshova, L G; Gordienko, E A; Kovalenko, I F

    2014-01-01

    We have studied permeability of isolated rat hepatocyte membranes for molecules of dimethyl sulfoxide (DMSO) at different hypertonicity of a cryoprotective medium. The permeability coefficient of hepatocyte membranes κ1 for DMSO molecules was shown to be the differential function of osmotic pressure between a cell and an extracellular medium. Ten-fold augmentation of DMSO concentration in the cryoprotective medium causes the decrease of permeability coefficients κ1 probably associated with the increased viscosity in membrane-adjacent liquid layers as well as partial limitations appeared as a result of change in cell membrane shape after hepatocyte dehydration. We have found out that in aqueous solutions of NaCl (2246 mOsm/l) and DMSO (2250 mOsm/l) the filtration coefficient L(p) in the presence of a penetrating cryoprotectant (L(pDMSO) = (4.45 ± 0.04) x 10(-14) m3/Ns) is 3 orders lower compared to the case with electrolyte (L(pNaCl) = (2.25 ± 0.25) x 10(-11) m3/Ns). This phenomenon is stipulated by the cross impact of flows of a cryoprotectant and water at the stage of cell dehydration. Pronounced lipophilicity of DMSO, geometric parameters of its molecule as well as the presence of large aqueous pores in rat hepatocyte membranes allow of suggesting the availability of two ways of penetrating this cryoprotectant into the cells by non-specific diffusion through membrane lipid areas and hydrophilic channels.

  5. Effects of Dimethyl Sulfoxide on Neuronal Response Characteristics in Deep Layers of Rat Barrel Cortex

    PubMed Central

    Soltani, Narjes; Mohammadi, Elham; Allahtavakoli, Mohammad; Shamsizadeh, Ali; Roohbakhsh, Ali; Haghparast, Abbas

    2016-01-01

    Introduction: Dimethyl sulfoxide (DMSO) is a chemical often used as a solvent for water-insoluble drugs. In this study, we evaluated the effect of intracerebroventricular (ICV) administration of DMSO on neural response characteristics (in 1200–1500 μm depth) of the rat barrel cortex. Methods: DMSO solution was prepared in 10% v/v concentration and injected into the lateral ventricle of rats. Neuronal spontaneous activity and neuronal responses to deflection of the principal whisker (PW) and adjacent whisker (AW) were recorded in barrel cortex. A condition test ratio (CTR) was used to measure inhibitory receptive fields in barrel cortex. Results: The results showed that both PW and AW evoked ON and OFF responses, neuronal spontaneous activity and inhibitory receptive fields did not change following ICV administration of DMSO. Conclusion: Results of this study suggest that acute ICV administration of 10% DMSO did not modulate the electrophysiological characteristics of neurons in the l deep ayers of rat barrel cortex. PMID:27563414

  6. Protective effect of dimethyl sulfoxide on acute myocardial infarction in rats.

    PubMed

    Parisi, Antonio; Alfieri, Alessio; Mazzella, Marialuisa; Mazzella, Antonio; Scognamiglio, Mattia; Scognamiglio, Gianluigi; Mascolo, Nicola; Cicala, Carla

    2010-01-01

    Dimethyl sulfoxide (DMSO) is an organic compound widely used as solvent in biological studies and as vehicle for drug administration. DMSO has been shown to possess several biological effects, including antioxidant, anti-inflammatory, antinociceptive effects, and it has been proposed to be therapeutic in several disorders, such as gastrointestinal diseases, rheumatologic diseases, and for the treatment of several manifestations of amyloidosis. To better define the biological profile of DMSO, we investigated its effect on an in vivo model of acute myocardial infarction in rats, caused by left anterior descending coronary artery ligation. Our results show that pretreatment of rats with intraperitoneal (ip) DMSO (500 microL/Kg) for 3 consecutive days before left anterior descending coronary artery ligation significantly (P < 0.05) reduced cardiac damage from 18.75 +/- 4.88% (n = 12) to 4.46 +/- 2.01% (n = 8); serum levels of troponin I from 29.35 +/- 12.32 ng/mL (n = 8) to 2.95 +/- 1.32 ng/mL (n = 4); and serum levels of myoglobin from 46.86 +/- 10.35 ng/mL (n = 7) to 13.75 +/- 0.85 ng/mL (n = 4). Our data demonstrate that DMSO has a protective effect in a model of acute myocardial infarction in rats. PMID:19904216

  7. The Role of Dimethyl Sulfoxide in the Reductive Dissolution of Iron in Marine Aerosols

    NASA Astrophysics Data System (ADS)

    Key, J. M.; Johansen, A. M.

    2003-12-01

    Very little is known about the effects of atmospheric iron (Fe) deposition from aeolian dusts into the remote oceans and the role it plays as a key nutrient for photosynthesis in marine phytoplankton in high nutrient low chlorophyll (HNLC) waters. Several in situ iron fertilization studies in HNLC regions have reported increases in chlorophyll a concentrations, nutrient and carbon uptake, and the release of various biogenic gases which have the potential to directly and indirectly impact global climate. Of particular interest in the present study is the indirect effect of dimethyl sulfoxide (DMSO) as part of a positive feedback cycle that may exist between such biogenically derived reduced sulfur compounds and crustal derived iron in the atmosphere over remote oceanic regions. To determine whether DMSO can lead to larger atmospheric concentrations of bioavailable iron in the form of Fe(II), photochemical simulation experiments were carried out using synthetic ferrihydrite (Fe5HO8ṡ4H2O) in the presence of DMSO. During these experiments DMSO oxidation products, such as methane sulfonic acid (MSA), methane sulfinic acid (MSIA), and sulfate (SO42-), were quantified by means of ion chromatography (IC), while Fe(II) was determined spectrophotometrically by complexation with ferrozine. Preliminary results suggest that current ambient DMSO levels are too low to play a significant role in the reductive dissolution of iron hydroxide in aerosol particles. However, increased DMSO levels may enhance bioavailability of iron, thus potentially closing the gap in the positive feedback cycle.

  8. Dimethyl Sulfoxide Perturbs Cell Cycle Progression and Spindle Organization in Porcine Meiotic Oocytes

    PubMed Central

    Li, Xuan; Wang, Yan-Kui; Song, Zhi-Qiang; Du, Zhi-Qiang; Yang, Cai-Xia

    2016-01-01

    Meiotic maturation of mammalian oocytes is a precisely orchestrated and complex process. Dimethyl sulfoxide (DMSO), a widely used solvent, drug, and cryoprotectant, is capable of disturbing asymmetric cytokinesis of oocyte meiosis in mice. However, in pigs, DMSO’s effect on oocyte meiosis still remains unknown. We aimed to evaluate if DMSO treatment will affect porcine oocyte meiosis and the underlying molecular changes as well. Interestingly, we did not observe the formation of the large first polar body and symmetric division for porcine oocytes treated with DMSO, contrary to findings reported in mice. 3% DMSO treatment could inhibit cumulus expansion, increase nuclear abnormality, disturb spindle organization, decrease reactive oxygen species level, and elevate mitochondrial membrane potential of porcine oocytes. There was no effect on germinal vesicle breakdown rate regardless of DMSO concentration. 3% DMSO treatment did not affect expression of genes involved in spindle organization (Bub1 and Mad2) and apoptosis (NF-κB, Pten, Bcl2, Caspase3 and Caspase9), however, it significantly decreased expression levels of pluripotency genes (Oct4, Sox2 and Lin28) in mature oocytes. Therefore, we demonstrated that disturbed cumulus expansion, chromosome alignment, spindle organization and pluripotency gene expression could be responsible for DMSO-induced porcine oocyte meiotic arrest and the lower capacity of subsequent embryo development. Our results provide new insights on DMSO’s effect on porcine oocyte meiosis and raise safety concerns over DMSO’s usage on female reproduction in both farm animals and humans. PMID:27348312

  9. Methionine Sulfoxide Reductases Protect against Oxidative Stress in Staphylococcus aureus Encountering Exogenous Oxidants and Human Neutrophils

    PubMed Central

    Pang, Yun Yun; Schwartz, Jamie; Bloomberg, Sarah; Boyd, Jeffrey M; Horswill, Alexander R.; Nauseef, William M.

    2013-01-01

    To establish infection successfully, S. aureus must evade clearance by polymorphonuclear neutrophils (PMN). We studied the expression and regulation of the methionine sulfoxide reductases (Msr) that are involved in the repair of oxidized staphylococcal proteins and investigated their influence over the fate of S. aureus exposed to oxidants or PMN. We evaluated a mutant deficient in msrA1 and msrB for susceptibility to hydrogen peroxide, hypochlorous acid and PMN. The expression of msrA1 in wild-type bacteria ingested by human PMN was assessed by real-time PCR. The regulation of msr was studied by screening a library of two-component regulatory system (TCS) mutants for altered msr responses. Relative to the wild-type, bacteria deficient in Msr were more susceptible to oxidants and to PMN. Upregulation of staphylococcal msrA1 occurred within the phagosomes of normal PMN and PMN deficient in NADPH oxidase activity. Furthermore, PMN granule-rich extract stimulated the upregulation of msrA1. Modulation of msrA1 within PMN was shown to be partly dependent on the VraSR TCS. Msr contributes to staphylococcal responses to oxidative attack and PMN. Our study highlights a novel interaction between the oxidative protein repair pathway and the VraSR TCS that is involved in cell wall homeostasis. PMID:24247266

  10. Electrochemical machining of gold microstructures in LiCl/dimethyl sulfoxide.

    PubMed

    Ma, Xinzhou; Bán, Andreas; Schuster, Rolf

    2010-02-22

    LiCl/dimethyl sulfoxide (DMSO) electrolytes were applied for the electrochemical micromachining of Au. Upon the application of short potential pulses in the nanosecond range to a small carbon-fiber electrode, three-dimensional microstructures with high aspect ratios were fabricated. We achieved machining resolutions down to about 100 nm. In order to find appropriate machining parameters, that is, tool and workpiece rest potentials, the electrochemical behavior of Au in LiCl/DMSO solutions with and without addition of water was studied by cyclic voltammetry. In waterless electrolyte Au dissolves predominantly as Au(I), whereas upon the addition of water the formation of Au(III) becomes increasingly important. Because of the low conductivity of LiCl/DMSO compared with aqueous electrolytes, high machining precision is obtained with moderately short pulses. Furthermore, the redeposition of dissolved Au can be effectively avoided, since Au dissolution in LiCl/DMSO is highly irreversible. Both observations render LiCl/DMSO an appropriate electrolyte for the routine electrochemical micromachining of Au. PMID:20017182

  11. Dissolution of brominated epoxy resins by dimethyl sulfoxide to separate waste printed circuit boards.

    PubMed

    Zhu, Ping; Chen, Yan; Wang, Liangyou; Qian, Guangren; Zhang, Wei Jie; Zhou, Ming; Zhou, Jin

    2013-03-19

    Improved methods are required for the recycling of waste printed circuit boards (WPCBs). In this study, WPCBs (1-1.5 cm(2)) were separated into their components using dimethyl sulfoxide (DMSO) at 60 °C for 45 min and a metallographic microscope was used to verify their delamination. An increased incubation time of 210 min yielded a complete separation of WPCBs into their components, and copper foils and glass fibers were obtained. The separation time decreased with increasing temperature. When the WPCB size was increased to 2-3 cm(2), the temperature required for complete separation increased to 90 °C. When the temperature was increased to 135 °C, liquid photo solder resists could be removed from the copper foil surfaces. The DMSO was regenerated by rotary decompression evaporation, and residues were obtained. Fourier transform infrared spectroscopy (FT-IR), thermal analysis, nuclear magnetic resonance, scanning electron microscopy, and energy-dispersive X-ray spectroscopy were used to verify that these residues were brominated epoxy resins. From FT-IR analysis after the dissolution of brominated epoxy resins in DMSO it was deduced that hydrogen bonding may play an important role in the dissolution mechanism. This novel technology offers a method for separating valuable materials and preventing environmental pollution from WPCBs.

  12. Specific reduction of N,N-dimethylnitrosamine mutagenicity in Drosophila melanogaster by dimethyl sulfoxide

    SciTech Connect

    Brodberg, R.K.; Mitchell, M.J.; Smith, S.L.; Woodruff, R.C.

    1988-01-01

    Dimethyl sulfoxide (DMSO) used as a solvent has been observed to complicate mutagenicity screens by interacting with tested chemicals to yield false positive or negatives. The authors have used DMSO as a solvent in the Drosophila melanogaster recessive sex-linked lethal mutation assay and find that it reduces, but does not abolish, the detectable mutagenicity of N,N-dimethylnitrosamine (DMN). Its use as a solvent with procarbazine, another promutagen, shows no effect on mutagenicity in Drosophila. DMSO does not exhibit a general inhibitory action on microsome activity when ecdysone 20-monooxygenase activity is used as a measure of cytochrome P-450 activity. They were unable to detect the low DMN demethylase activity in the strain used. Hence, the inhibitory effect of DMSO in Drosophila at both the physiological and biological level appears to be limited and not general in action. Because DMN and DMSO are similar in structure, it is possible that DMSO is interacting with a DMN demethylase in Drosophila. This might lead to a reduction in the conversion of DMN to a mutagen. Consequently, from the results of this study and others DMSO should be used cautiously as a solvent in Drosophila mutagen screening.

  13. Ion transport properties of magnesium bromide/dimethyl sulfoxide non-aqueous liquid electrolyte.

    PubMed

    Sheha, E

    2016-01-01

    Nonaqueous liquid electrolyte system based dimethyl sulfoxide DMSO and magnesium bromide (MgBr2) is synthesized via 'Solvent-in-Salt' method for the application in magnesium battery. Optimized composition of MgBr2/DMSO electrolyte exhibits high ionic conductivity of 10(-2) S/cm at ambient temperature. This study discusses different concentrations from 0 to 5.4 M of magnesium salt, representing low, intermediate and high concentrations of magnesium salt which are examined in frequency dependence conductivity studies. The temperature dependent conductivity measurements have also been carried out to compute activation energy (Ea ) by least square linear fitting of Arrhenius plot: 'log σ - 1/T. The transport number of Mg(2+) ion determined by means of a combination of d.c. and a.c. techniques is ∼0.7. A prototype cell was constructed using nonaqueous liquid electrolyte with Mg anode and graphite cathode. The Mg/graphite cell shows promising cycling.

  14. Field response of Colorado potato beetle to the (R)-enantiomer of the male-produced aggregation pheromone CPB I and determination of activity of blends of the (S)- and (R)-enantiomers of the pheromone

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adult Colorado potato beetles (CPB) are attracted to (S)-3,7-dimethyl-2-oxo-oct-6-ene-1,3-diol [(S)-CPB I], a male-produced aggregation pheromone. Studies were conducted to determine if the opposite enantiomer of the pheromone, (R)-CPB I had an effect on CPB in the field. Results revealed no differe...

  15. ENANTIOMER FRACTIONS OF CHLORDANE COMPOUNDS IN SEDIMENT SAMPLES FROM U.S. GEOLOGICAL SURVEY SITES IN LAKES, RIVERS AND RESERVOIRS

    EPA Science Inventory

    The environmental behavior of the enantiomers of cis- and trans-chlordane has been the topic of much research since the first chiral separations on cyclodextrin gas chromatography (GC) columns. When chlordane is manufactured, it is always a racemic mixture (equal portion of two e...

  16. Enantioselective synthesis of both enantiomers of methyl dihydrojasmonate using solid-liquid asymmetric phase-transfer catalysis.

    PubMed

    Perrard, T; Plaquevent, J C; Desmurs, J R; Hébrault, D

    2000-09-21

    Both enantiomers of methyl dihydrojasmonate (-)-1 and (+)-1 were obtained by a short route using asymmetric Michael addition of dimethyl malonate onto pentyl enone 3, followed by nonracemizing demethoxycarbonylation. The key enantioselective step involves a new system of asymmetric solid-liquid phase-transfer catalysis using solvent-free conditions. Enantiomeric excess as high as 90% (91% yield) was achieved.

  17. Application of maltodextrin as chiral selector in capillary electrophoresis for quantification of amlodipine enantiomers in commercial tablets.

    PubMed

    Nojavan, Saeed; Pourmoslemi, Shabnam; Behdad, Hamideh; Fakhari, Ali Reza; Mohammadi, Ali

    2014-08-01

    Maltodextrin was investigated as a chiral selector in capillary electrophoresis (CE) analysis of amlodipine (AM) enantiomers. For development of a stereoselective CE method, various effective parameters on the enantioseparation were optimized. The best results were achieved on an uncoated fused silica capillary at 20 °C using phosphate buffer (100 mM, pH 4) containing 10% w/v maltodextrin (dextrose equivalent value 4-7). The UV detector was set at 214 nm and a constant voltage of 20 kV was applied. The range of quantitation was 2.5-250 µg/mL (R(2)  > 0.999) for both enantiomers. Intra- (n = 5) and interday (n = 3) relative standard deviation (RSD) values were less than 7%. The limits of quantitation and detection were 1.7 µg/mL and 0.52 µg/mL, respectively. Recoveries of R(+) and S(-) enantiomers from tablet matrix were 97.2% and 97.8%, respectively. The method was applied for the quantification of AM enantiomers in commercial tablets. Also, the enantioseparation capability of heparin was evaluated and the results showed that heparin did not have any chiral selector activity in this study.

  18. An Enantiomer of an Oral Small-Molecule TSH Receptor Agonist Exhibits Improved Pharmacologic Properties.

    PubMed

    Neumann, Susanne; Padia, Umesh; Cullen, Mary Jane; Eliseeva, Elena; Nir, Eshel A; Place, Robert F; Morgan, Sarah J; Gershengorn, Marvin C

    2016-01-01

    We are developing an orally available small-molecule, allosteric TSH receptor (TSHR) agonist for follow-up diagnostics of patients with thyroid cancer. The agonist C2 (NCGC00161870) that we have studied so far is a racemic mixture containing equal amounts of two enantiomers, E1 and E2. As enantiomers of many drugs exhibit different pharmacologic properties, we assessed the properties of E1 and E2. We separated the two enantiomers by chiral chromatography and determined E2 as the (S)-(+) isomer via crystal structure analysis. E1 and E2 were shown to bind differently to a homology model of the transmembrane domain of TSHR in which E2 was calculated to exhibit lower binding energy than E1 and was, therefore, predicted to be more potent than E1. In HEK293 cells expressing human TSHRs, C2, E1, and E2 were equally efficacious in stimulating cAMP production, but their potencies were different. E2 was more potent (EC50 = 18 nM) than C2 (EC50 = 46 nM), which was more potent than E1 (EC50 = 217 nM). In primary cultures of human thyrocytes, C2, E1, and E2 stimulated increases in thyroperoxidase mRNA of 92-, 55-, and 137-fold and in sodium-iodide symporter mRNA of 20-, 4-, and 121-fold above basal levels, respectively. In mice, C2 stimulated an increase in radioactive iodine uptake of 1.5-fold and E2 of 2.8-fold above basal level, whereas E1 did not have an effect. C2 stimulated an increase in serum T4 of 2.4-fold, E1 of 1.9-fold, and E2 of 5.6-fold above basal levels, and a 5-day oral dosing regimen of E2 increased serum T4 levels comparable to recombinant human TSH (rhTSH, Thyrogen(®)). Thus, E2 is more effective than either C2 or E1 in stimulating thyroid function and as efficacious as rhTSH in vivo. E2 represents the next step toward developing an oral drug for patients with thyroid cancer. PMID:27512388

  19. Disposition and effects of flurbiprofen enantiomers in human serum and blister fluid

    PubMed Central

    Oelkers, R.; Neupert, W.; Williams, K. M.; Brune, K.; Geisslinger, G.

    1997-01-01

    Aims To investigate the pharmacokinetics of the enantiomers of flurbiprofen and inhibition of prostanoid production in blister fluid and serum. Methods Eleven healthy volunteers received 75 mg R-, 75 mg S-flurbiprofen or no medication in a randomized 3-way cross-over study. Flurbiprofen concentrations were determined by h.p.l.c. TXB2 and PGE2 were determined by enzyme immunoassay and chemiluminescence immunoassay respectively. Results S-flurbiprofen produced almost complete (>99%vs baseline) inhibition of thromboxane B2 (TXB2 ) in serum in all volunteers and significant inhibition of prostaglandin E2 (PGE2 ) generation in blister fluid, but there was a considerable inter-individual variation in the response ranging from −78 to +190% change from control PGE2 AUC. After administration of R-flurbiprofen, there was a mean maximum TXB2 inhibition of 65.2±15.0% in serum but no significant changes of PGE2 levels in blister fluid were observed. The pharmacokinetic parameters in serum and blister fluid were not significantly different between enantiomers. R- to S-inversion did not occur to a clinically relevant extent. For R-flurbiprofen, the complex rate constant of transfer into blister fluid was greater at the u.v.-exposed site (0.110±0.050) than at the control site (0.079±0.026, P<0.05) which corresponded to a higher AUC and Cmax of R-flurbiprofen in u.v.-exposed blister as compared with control. For inhibition of TXB2 generation after administration of S-flurbiprofen, a sigmoidal log-linear concentration–response relationship was established in all subjects (EC50: 0.123±0.092 μg ml−1 ). In contrast, inhibition of PGE2 production in blister showed no clear concentration-response relationship when correlated with concentrations of S-flurbiprofen in either serum or blister fluid. After administration of R-flurbiprofen, no concentration-effect relationship could be established. Conclusions It is concluded that the blister model may have

  20. Antagonistic interaction of selenomethionine enantiomers on methylmercury toxicity in the microalgae Chlorella sorokiniana.

    PubMed

    Moreno, Fernando; García-Barrera, Tamara; Gómez-Jacinto, Verónica; Gómez-Ariza, José Luis; Garbayo-Nores, Inés; Vílchez-Lobato, Carlos

    2014-02-01

    The protective effect of selenium against mercury toxicity is well known especially between selenomethionine and methylmercury and it has been studied in several living organisms, however information is lacking about the interaction of these species in Chlorella. Investigation into which chiral form of selenomethionine effectively acts against the toxic effects of methylmercury has not previously been carried out. In the present work, two control cultures and two cultures of C. sorokiniana were grown in standard medium with D,L-SeMet, L-SeMet or D-SeMet. After the experiment was started up MeHg(+) was added periodically to the cultures containing D,L-SeMet, L-SeMet, D-SeMet and to one of the control batches. The results show that both SeMet enantiomers counteract the toxicity of MeHg(+), by markedly increasing the total content of chlorophyll, carotenoids, as well as the dry weight and light dependent oxygen production, compared to the culture which is non pre-treated with SeMet and is only exposed to MeHg(+). The levels of MeHg(+) measured in cells are lower in the cultures pre-treated with SeMet indicating that the passage of MeHg(+) into the cells is negligible when carried out in the presence of SeMet, or that SeMet enhances the release of MeHg(+). On the other hand, L-SeMet is directly involved in the detoxification of MeHg(+), but the involvement of D-SeMet occurs only indirectly since it has been neither identified in the medium nor in C. sorokiniana after supplementation with this enantiomer. It may be that D-SeMet is transformed into SeMeSec and L-SeMet. Moreover, SeMeSec is almost totally released from the cells after 72 hours. No mercury-selenium complex was detected but, since the summation of the different species identified accounted only for 77% of the total selenium and mercury measured directly after sample digestion, it is possible that they are present in the form of an undetected Se-Hg complex. This hypothesis is supported by the decrease of