Liquiritigenin (7,4'-dihydroxyflavone), the primary active component of a traditional Chinese medicine Glycyrrhizae radix, has a wide range of pharmacological activities. Six oxidative metabolites of liquiritigenin (7,3',4'-trihydroxyflavone, a hydroxyl quinine metabolite, two A-ring dihydroxymetabolites, 7,4'-dihydroxyflavone, and 7-hydroxychromone) have been detected in rat ...
PubMed
Novel diacrylates are prepared by reacting a monohydroxylated acrylic monomer with a polyisocyanate. The reaction product may be polymerized by subjecting to ionizing irradiation, actinic light or to free radical catalysts to form a useful coating material. The diacrylates may also be copolymerized with other radiation sensitive materials. 6 claims, no drawings.
Energy Citations Database
Novel diacrylates are prepared by reacting a monohydroxylated acrylic monomer with a polyisocyanate. The reaction product may be polymerized by subjecting to ionizing irradiation, actinic light or to free radical catalysis to form a useful coating material. The diacrylates may also be copolymerized with other radiation sensitive materials.
... above. Finally, hydroxylated fatty acids were converted into methyl ester and trimethylsilyl ether derivatives as described previously (29). Gas Chromatography-Mass ... ...
NBII National Biological Information Infrastructure
A potent synthetic cannabinoid receptor agonist, JHW-018, was recently detected as one of the most prominent active agents in abusively used incenses such as Spice and other herbal blends. The high pharmacological and addictive potency of JWH-018 highlights the importance of elucidating the metabolism of JWH-018, without which a meaningful insight into its pharmacokinetics and its toxicity would ...
The case is described of a tumour of the iris and ciliary body--a ring type melanoma--primarily diagnosed and treated as pigmentary glaucoma.Images
PubMed Central
... for developing new approaches to TAT: (a) ring synthetic methods from small molecules; (b) partially destructed hexamethylenetetramine (DAPT); (c ...
DTIC Science & Technology
... through the esophagus and into the stomach. A ring of muscle at the bottom of the esophagus, ... the esophagus, beyond the upper esophageal sphincter (a ring of muscle at the top of the esophagus), ...
MedlinePLUS
Eight actinomycetes of the genera Amycolatopsis and Streptomyces were tested for the degradation of aromatic compounds by growth in a liquid medium containing benzoate, monohydroxylated benzoates, or quinate as the principal carbon source. Benzoate was converted to catechol. The key intermediate in the degradation of salicylate was either catechol or gentisate, while ...
A preharvest method to reduce the accumulation of limonoate A-ring lactone (LARL), the precursor of the principal bitter limonoid constituent of citrus juice, is described. In the method of the invention, auxins are applied two or more times in an effecti...
National Technical Information Service (NTIS)
In the mid-eighties, three new arachidonic acid metabolites were discovered in burned guinea pigs; their probable structures corresponded to monohydroxylized derivatives of arachidonic acid in positions 16, 17 and 18. In the study, all of the optically pu...
A pillar[5]arene dimer was synthesized by linking a mono-hydroxylated pillar[5]arene with 1,4-bis(bromomethyl)benzene. The pillar[5]arene dimer formed stronger complexes with n-alkanes than did a monomeric pillar[5]arene. PMID:21858335
A process for stabilizing mixtures of gasoline and methanol containing at least 30% by volume of methanol is disclosed wherein a primary, linear or branched chain monohydroxylated aliphatic saturated alcohol containing from 8 to 15 carbon atoms or a mixture of such alcohols, is added to the gasoline/methanol mixture. The stabilized mixtures described herein are useful as a ...
Pseudomonas putida F1 contains a multicomponent enzyme system, toluene dioxygenase, that converts toluene and a variety of substituted benzenes to cis-dihydrodiols by the addition of one molecule of molecular oxygen. Toluene-grown cells of P. putida F1 al...
Available online 30 January 2006 Abstract We show that the C40 carotenoid desaturase CrtI from Pantoea), and the subsequent desaturation of this backbone by CrtI in an atypical manner. Under some conditions, the C40, C45, and C50 carotenoid backbones synthesized in E. coli were monohydroxylated; their desaturation by Crt
E-print Network
AimsThe aims of this study were to examine the in vitro enzyme kinetics and CYP isoform selectivity of perhexiline monohydroxylation using human liver microsomes.MethodsConversion of rac-perhexiline to monohydroxyperhexiline by human liver microsomes was assessed using a high-performance liquid chromatography assay with precolumn derivatization to measure the formation rate of ...
Under the conditions of C-C bond forming transfer hydrogenation, 1,3-propanediol 1 engages in double asymmetric carbonyl allylation to furnish the C(2)-symmetric diol 2. Double ozonolysis of 2 followed by TBS protection delivers aldehyde 3, which is subject to catalyst directed carbonyl reverse prenylation via transfer hydrogenation to deliver neopentyl alcohol 4 and, ultimately, the bryostatin ...
Under the conditions of C-C bond forming transfer hydrogenation, 1,3-propanediol 1 engages in double asymmetric carbonyl allylation to furnish the C2-symmetric diol 2. Double ozonolysis of 2 followed by TBS protection delivers aldehyde 3, which is subject to catalyst directed carbonyl prenylation via transfer hydrogenation to deliver neopentyl alcohol 4 and, ultimately, the ...
In continuation of our current research project we are trying to obtain new synthetic approaches to the TAT molecule along the following three pathways (cf. previous Interim Reports): (a) ring synthetic methods from small molecules; (b) selective bridge r...
At present we are continuing our synthetic strategy on three different pathways: (a) ring synthetic methods from easily accessible small molecules without template effect, (b) half-synthetic methods starting from partially destructed hexamethylenetramine,...
This dramatic close-up of Tethys shows the large crater Penelope lying near ..... PIA08975: A-Ring Odyssey Full Resolution: TIFF (1.042 MB) JPEG (39.55 kB) ...
NASA Website
Pseudomonas fluorescens 5R, a naphthalene-degrading bacterium isolated from manufactured gas plant soil contaminated with polycyclic aromatic hydrocarbons, was examined for its degradative capacity of a number of substituted naphthalenes. In general, those compounds substituted on only one ring with an electrically neutral substituent were found to be transformed primarily to substituted salicylic ...
Scope: Monohydroxylation of alternariol (AOH) and alternariol-9-methyl ether (AME) has previously been reported as a prominent metabolic route under cell-free conditions. This pathway gives rise to several catechol metabolites and may therefore be of toxicological relevance. Methods and results: To clarify whether hydroxylation of AOH and AME occurs under in vivo-like ...
The metabolism of 10 different congeners of polychlorinated biphenyls (PCBs) was tested in cell cultures of 12 different plant species. The rate of metabolism was determined through comparison with cells inactivated by treatment with perchloric acid. The metabolism of defined PCB congeners was strongly dependent on the plant species. In particular, two Fabaceae species exhibited high capacities ...
We characterized the ability of a yeast to cleave the aromatic structure of the dioxin-like compound dibenzofuran. The yeast strain was isolated from a dioxin-contaminated soil sample and identified as Trichosporon mucoides. During incubation of glucose-pregrown cells with dibenzofuran, six major metabolites were detected by high-performance liquid chromatography. The formation of four different ...
The Russian Federation prohibited the distribution of herbal mixtures with synthetic aminoalkylindoles JWH-018 and JWH-073, agonist cannabinoid receptors, on January 22, 2010. The lack or low content of their native compounds in urine requires detailed identification of their metabolites, which are excreted with urine and are present in blood. Using gas and liquid chromatography-mass spectrometry, ...
The biotransformation of [14C]4-n-nonylphenol (5 mg l(-1); 10 mg l(-1)) by Agrostemma githago cell suspensions was studied using a batch two-liquid-phase system (medium/n-hexadecane 200:1, v/v). The highly lipophilic 4-n-nonylphenol was applied via n-hexadecane phase. After 7 d of incubation, more than 85% of applied 4-n-nonylphenol was absorbed by the cells, and 40% was transformed to 10 ...
The larvicidal activity against Culex pipiens of all stereoisomers of dihydroguaiaretic acid (DGA) and secoisolariciresinol was measured, and these DGAs were found to be potent. Sixteen (-)-DGA derivatives were then newly synthesized to analyze their structure-activity relationship. Two derivatives monohydroxylated at the 3- or 4-position of the 7-phenyl group of DGA induced ...
Prohibition of some synthetic cannabimimetics (e.g., JWH-018, JWH-073 and CP 47497) in a number of countries has led to a rise in new compounds in herbal mixtures that create marijuana-like psychotropic effects when smoked. The cannabimimetic JWH-250 (1-pentyl-3-(2-methoxyphenylacetyl)indole) was identified in May 2009 by the German Federal Criminal Police as an new ingredient in herbal smoking ...
Biological macromolecules embedded in vitreous ice are known to suffer from charging while being imaged in an electron transmission cryomicroscope. We developed an electron beam coater that deposits conductive films onto the surface of frozen-hydrated specimens. The conductive films help to dissipate charge during electron irradiation of poorly conductive ice-embedded biological samples. We ...
NASA Astrophysics Data System (ADS)
The metabolism of hyperforin, one of the pharmacologically most active components of St. John's wort (Hypericum perforatum), was characterized in vitro using human liver microsomes and recombinant heterologously expressed P450 enzymes. A total of 57 hyperforin metabolites were detected. Of those, six were identified as monohydroxylations (M1-M6), while the others were formed ...
Overexpression of human CYP4Z1, a cytochrome P450 enzyme, has been correlated with poor prognosis in human cancer. However, its catalytic properties are not yet known. We expressed this P450 in Schizosaccharomyces pombe and demonstrate by whole-cell biotransformation assays CYP4Z1-dependent in-chain hydroxylation of lauric and myristic acid, which in both cases leads to the formation of four ...
The authors studied adsorption of copper and zinc on three different soils: a brown silty soil, an Oxisol, and a Podzol. They determined the amounts adsorbed and the shapes of adsorption isotherms as a function of the pH of the adsorbing medium at a constant ionic strength. The adsorbed amount-pH relationship depended strongly on the natures of the metallic cation and of the soil. The pH greatly ...
... non-natives in Canada and the United States. Ringing programmes at Arctic breeding colonies have been used ... Bay and at Prince Leopold Island (Gaston 2002a). Ringing of nestling Br�nnich's guillemots ha...
A stereoselective synthesis of agelastatin A, a potent cytotoxin and inhibitor of osteopontin (OPN)�mediated neoplastic transformations, has been accomplished in 14 steps (12 operations) with an approximate overall yield of 8%. Notable features of this route include the direct manner in which the pyrroloketopiperazine A-ring of the target is generated and the efficient ...
A convergent and effective synthesis of the pyrrolopyrrole substructure (CDEFG) of the isoquinocyclines is reported. A key step is a tin-lithium exchange of an imidato-alkenyltin compound (a ring G equivalent) and the subsequent acylation with a lactone. The resulting acetal is used successfully for the ring F closure to the pyrrolopyrrole. The sole ...
extremely fast roughing system for normal testing. Fig- ure 4 shows a pressure profile for fast pumpdown. Table 2 .... (5) Scaffold hoist-a ring scaffold suspended from .... trolley travels on the monorail at speeds of 5 and 15 ft/min . ...
Several polycyclic aromatic hydrocarbons (PAH) have been identified in recent Amazon River and Cariaco Trench sediments. The skeletal structures of these compounds suggest triterpenoid precursors. The tetracyclic compounds seem to result from A-ring cleavage and the pentacyclic compounds from aromatization which begins with ring A and proceeds through ring D. These compounds ...
loss may be accompanied by tinnitus--a ringing, buzzing, or roaring in the ears or head--which may subside over time. Hearing loss and tinnitus may be experienced in one or both ears, and tinnitus may damage the structure of hair cells, resulting in hearing loss and tinnitus, although the process occurs
. Stewart Peck (Leiodidae, Hydro- philidae), Dr. David Kavanaugh (Carabidae), Dr. Robb Bennett (Agelenidae Carabidae Scaphinotus angusticollis Opportunistic predator Mannerheim Opportunistic predator Carabidae Pterostichus crenicollis LeConte Opportunistic predator Carabidae P. amethystinus Mannerheim Opportunistic
In continuation and implementation of my recent travel & conference report dated July 24, 1987, we are still following up our three general synthetic strategies for developing new approaches to TAT: (a) ring synthetic methods from small molecules; (b) par...
f�r positiv aufgeladene Staubteilchen kommen der �u�ere Rand von Saturns A-Ring sowie der d�nne E-Ring Dienst: Dr. Andreas Trepte (-1238) ISSN 0170-4656 Saturn wirkt als kosmische Staubschleuder Staubdetektor an den Saturn entdeckt. Bereits in einer Entfernung von 70 Millionen Kilometern registrierte der Detektor
Delayed bitterness is a well-known phenomenon in citrus juice and has a negative impact on juice quality. Bitterness results when the tasteless limonoic acid A-ring lactone (LARL) in juice is converted to the bitter compound limonin after juicing. Citrus varieties that produce juice that becomes bit...
Technology Transfer Automated Retrieval System (TEKTRAN)
The local environment of NiIII ions in the HNiO2 oxyhydroxide has been studied by Ni-K edge EXAFS and compared to those of various layered nickelates. The NiIII site in the ?(III)-HNiO2 phase exhibits a Jahn Teller distortion, as in LiNiO2 or NaNiO2, characterized by four Ni-O distances at 1.87 A&ring and two long ones at 2.03 A&ring. A very strong ...
experienced tinnitus or hearing impairment after attending a concert.(Tinnitus is a persistent ringing be detected with a hearing test. Excessive noise also may cause tinnitus,a ringing or buzzing sound in the ear.Similar to NIHL,tinnitus can be permanent. What Is NIHL? A decibelis a unit for measuring sound.The softest sound
...2010-07-01 false What are the requirements for ring life buoys? 149.320 Section 149.320 Navigation...149.320 What are the requirements for ring life buoys? (a) Ring life buoys must be approved under approval series...
Code of Federal Regulations, 2010
The non-steroidal anti-inflammatory drugs diclofenac (DCF) and mefenamic acid (MFA) were treated with the white rot fungus Phanerochaete sordida YK-624. DCF completely disappeared and MFA decreased by about 90% after 6 days of treatment. It was also confirmed that the fungus almost completely removed the acute lethal toxicity of DCF and MFA towards the freshwater crustacean Thamnocephalus ...
Tipranavir (TPV) is the first nonpeptidic protease inhibitor used for the treatment of drug-resistant HIV infection. Clinically, TPV is coadministered with ritonavir (RTV) to boost blood concentrations and increase therapeutic efficacy. The mechanism of metabolism-mediated drug interactions associated with RTV-boosted TPV is not fully understood. In the current study, TPV metabolism was ...
Ebracteolata compound B (ECB) is one major active component of both Euphorbia ebracteolata and Euphorbia fischeriana, which have been extensively used as a tuberculocide in the Asian countries. The aim of our present study was to characterize ECB metabolism in human liver microsomes, HepG2 cells, and recombinant human enzymes. One monohydroxylation metabolite, determined by ...
Taranabant (N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2-{[5-(trifluoromethyl)pyridin-2-yl]oxy}propanamide or MK-0364) is an orally active inverse agonist of the cannabinoid 1 (CB-1) receptor that was under development for the management of obesity. The metabolism and excretion of taranabant were investigated following a single oral dose of 5?mg/201 ?Ci ...
Irosustat is a novel steroid sulfatase inhibitor for hormone-dependent cancer therapy. Its structure is a tricyclic coumarin-based sulfamate that undergoes desulfamoylation in aqueous solution, yielding the sulfamoyl-free derivative, 667-coumarin. The aim of the present work was to study the in vitro metabolism of irosustat, including its metabolic profile in liver microsomes and hepatocytes, the ...
The experimental data of Wubs and Beenackers on the oxidative absorption of H{sub 2}S into aqueous solutions of ferric chelates of ethylenediaminetetraacetic acid (EDTA) and hydroxyethylethylenediaminetriactic (HEDTA) were reinterpreted using a new penetration model for mass transfer parallel to chemical reaction. Different from the discussion by Wubs and Beenackers (1994), which was based on ...
Echinochloa phyllopogon (late watergrass) is a major weed of California rice (Oryza sativa) that has evolved cytochrome P450-mediated metabolic resistance to different herbicides with multiple modes of action. E. phyllopogon populations from Sacramento Valley rice fields have also recently shown resistance to the herbicide clomazone. Clomazone is a proherbicide that must be metabolized to ...
The abuse of stanozolol is quite widespread in Indian sport. Its analysis is challenging and this has led to the development of new methods to improve its detection. A method was developed and validated for the detection of the three main monohydroxylated metabolites of stanozolol. The excretion profile of these metabolites was studied in four healthy male volunteers. The ...
Polyphenols, chlorophylls, and carotenoids were characterized by HPLC-DAD-MS(n) in the pericarp of unripe to over-ripe 'Hong Huey' and 'Chacapat' litchi fruit at harvest and during subsequent storage (5 �C, 90% RH, 21 days). (-)-Epicatechin and A-type procyanidins always predominated quantitatively. Besides these ortho-diphenolic compounds, minor novel litchi flavonoids included ...
N-Me-anthranylaldoximes possess a hydrogen-bonded pseudocyclic A' ring in place of the typical phenolic A-ring that is characteristic of most estrogen receptor (ER) ligands. We have investigated the role played by substituents introduced into either one or both of the peripheral 3- and 4-phenyl rings in modulating ER binding affinity. ...
Taxol 1, a novel anticancer agent, isolated from Taxus brevifolia, is a member of the class of taxane diterpenes. Since its isolation and characterization many groups around the world using varied approaches have made significant contributions toward the assembly of the taxane framework and ultimately to taxol itself. The focus of this investigation was directed towards making a fully ...
Limonoate dehydrogenase from Rhodococcus fascians has been purified to electrophoretic homogeneity by a procedure that consists of ion-exchange, hydrophobic, and affinity chromatography. The native enzyme has a molecular mass of around 128,000 Da and appears to be composed of four similar subunits (30,000 Da each). The isoelectric point is 4.9 as determined by isoelectric focusing. The homogeneous ...
Epiceanothic acid (1) is a naturally occurring, but very rare pentacyclic triterpene with a unique pentacyclic triterpene (PT) structure. An efficient synthesis of 1 starting from betulin (3) has been accomplished in 12-steps with a total yield of 10% in our study. Compound 1 and selected synthetic intermediates were further evaluated as anti-HIV-1 agents, inhibitors of glycogen phosphorylase ...
Calcitriol is implicated in many cellular functions including cellular growth and differentiation thus explaining its anti-tumor effects. It was shown that gemini, the calcitriol derivative containing two side chain at C20, is also active in gene transcription with enhanced anti-tumor activity. We have now further optimized both the A-ring and the two side chains. The chemical structures of the ...
The contribution of the A-ring C(7) acetate to the function of bryostatin 1 has been investigated through synthesis and biological evaluation of an analogue incorporating this feature into the bryopyran core structure. No enhanced binding affinity for protein kinase C (PKC) was observed, relative to previously characterized analogues lacking the C(7) acetate. Functional assays showed biological ...
A close structural analogue of bryostatin 1, which differs from bryostatin 1 only by the absence of the C(30) carbomethoxy group (on the C(13) enoate of the B-ring), has been prepared by total synthesis. Biological assays reveal a crucial role for substitution in the bryostatin 1 A-ring in conferring those responses which are characteristic of bryostatin 1 and distinct from ...
The biotransformation of methandienone (17 beta-hydroxy-17 alpha-methylandrosta-1,4-dien-3-one) in human adults, more particularly the sequential reduction of its A-ring substituents, was investigated by gas chromatography-mass spectrometry. Two pairs of 17-epimeric tetrahydro diols resulting from the stereoselective reduction of the delta 4- and 3-oxo groups and of the delta ...
A simple and convenient method has been developed to prepare sulfates of anabolic 17 beta-hydroxy-17 alpha-methyl steroids. The sulfates of methandienone, 17 alpha-methyltestosterone, mestanolone, oxandrolone, and stanozolol were prepared. Different A-ring functions were not affected under the sulfation condition. The buffered hydrolyses of these sulfates provided the ...
A new series of ligands for the glucocorticoid receptor (GR) is described. SAR development was guided by docking 3 into the GR active site and optimizing an unsubstituted phenyl ring for key interactions found in the steroid A-ring binding pocket. To identify compounds with an improved side effect profile over marketed steroids the functional activity of compounds was ...
The leaves of the endemic Philippine plant, Dillenia philippinensis yielded 11 compounds including one new sulfated glucoside and a new seco-A-ring oleanane-type triterpenoid. The molecular structures of these compounds were elucidated by means of NMR, MS and other spectroscopic techniques, as well as by comparison with literature data. Anti-Leishmania activity and cytotoxic ...
Putidaredoxin (Pdx), a 106-residue globular protein consisting of a single polypeptide chain and a (2Fe-2S) cluster, is the physiological reductant of P-450{sub cam}, which in turn catalyzes the monohydroxylation of camphor by molecular oxygen. No crystal structure has been obtained for Pdx or for any closely homologous protein. The application of two-dimensional {sup 1}H NMR ...
A microbial population which transformed 3- and 4-picoline under sulfate-reducing conditions was isolated from a subsurface soil which had been previously exposed to different N-substituted aromatic compounds for several years. In the presence of sulfate, the microbial culture transformed 3- and 4-picoline (0.4 mM) within 30 days. From the amounts of ammonia released and of sulfide that were ...
A novel approach is presented for studying the chemical interaction between receptor binding sites and ligands. Monohydroxylated polyaromatic compounds were found to be environmentally sensitive ligands when applying a special mode of fluorescence: fluorescence line-narrowing spectroscopy (FLNS). With this technique, solvent dependencies and ligand-receptor interactions can be ...
Flavan-3-ols, such as green tea catechins represent a major group of phenolic compounds with significant medicinal properties. We describe the construction and optimization of Escherichia coli recombinant strains for the production of mono- and dihydroxylated catechins from their flavanone and phenylpropanoid acid precursors. Use of glucose minimal medium, Fe(II), and control of oxygen ...
An assay based on isotope-dilution mass spectrometry with deuterium-labeled internal standards was developed for simultaneous quantification of cholest-5-ene-3 beta,7 alpha-diol (7 alpha-hydroxycholesterol), cholest-5 beta,6 beta-epoxy-3 beta-ol (cholesterol-5 beta,6 beta-epoxide), cholest-5 alpha,6 alpha-epoxy-3 beta-ol (cholesterol-5 alpha,6 alpha-epoxide), cholest-5-en-7-one-3 beta-ol ...
This paper demonstrates for the first time transformation of a series of steroids (progesterone, androst-4-en-3,17-dione, testosterone, pregnenolone and dehydroepiandrosterone) by the thermophilic fungus Rhizomucor tauricus. All transformations were found to be oxidative (monohydroxylation and dihydroxylation) with allylic hydroxylation the predominant route of attack ...
Enantiomeric PLAs, poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), are known to form stereocomplexes. In this work, by using controlled ring-opening polymerization of L- and D-lactides from monohydroxyl-terminated hydrophilic poly(ethylene oxide) (PEO) and hydrophobic poly(ethylene-co-1-butene) (PEB) oligomers, respectively, well-defined PEO-b-PLLA (2k-5.4k) and PEB-b-PDLA ...
Microbial steroid dehydrogenation is quite common. The reaction seems to occur mainly in bacteria and usually results in hydrogen abstraction from positions C(1)-C(2) and/or C(4)-C(5) with occasional aromatisation of ring A. We have screened large numbers of fungal cultures for their ability to monohydroxylate steroids at unusual sites and in the course of our investigations ...
Menthofuran is a monoterpene present in mint plants that is oxidized by mammalian cytochrome P450 (CYP) to hepatotoxic metabolites. Evidence has been presented that p-cresol and other unusual oxidative products are metabolites of menthofuran in rats and that p-cresol may be responsible in part for the hepatotoxicity caused by menthofuran [ Madyastha, K. M. and Raj, C. P. (1992) Drug Metab. Dispos. ...
Laccase activity in plants results in the formation of a number of brown pigments, often referred to as tannins. Laccase-dependent pigment production is also catalogued in numerous fungal and bacterial species. The laccase of the haploid yeast Cryptococcus neoformans forms melanin-like pigmentation outside the cell wall in the presence of exogenous substrates. While this process is a contributing ...
Strength and stability of laser-welded tissue may be influenced, in part, by effects of laser exposure on collagen crosslinking. We therefore studied effects of diode laser exposure (805 nm, 1-8 watts, 30 seconds) + indocyanine green dye (ICG) on calf tail tendon collagen crosslinks. Effect of ICG dye alone on crosslink content prior to laser exposure was investigated; unexpectedly, we found that ...
The enniatins are a group of more than 20 cyclic depsipeptides from fungi with numerous biological effects. Enniatin B is commonly one of the principal analogues in species of the genus Fusarium, known to have ionophoric, antibiotic and insecticidal activity. In the present study, enniatin B was incubated with rat, dog and human liver microsomes. The compound was extensively metabolised, and 12 ...
MauG is a diheme enzyme responsible for the posttranslational modification of two tryptophan residues to form the tryptophan tryptophylquinone (TTQ) cofactor of methylamine dehydrogenase (MADH). MauG converts preMADH, containing monohydroxylated {beta}Trp{sup 57}, to fully functional MADH by catalyzing the insertion of a second oxygen atom into the indole ring and covalently ...
MauG is a diheme enzyme responsible for the posttranslational modification of two tryptophan residues to form the tryptophan tryptophylquinone (TTQ) cofactor of methylamine dehydrogenase (MADH). MauG converts preMADH, containing monohydroxylated betaTrp57, to fully functional MADH by catalyzing the insertion of a second oxygen atom into the indole ring and covalently linking ...
MauG is a di-heme enzyme responsible for the posttranslational modification of two tryptophan residues to form the tryptophan tryptophylquinone cofactor (TTQ) of methylamine dehydrogenase (MADH). MauG converts preMADH, containing monohydroxylated-?Trp57, to fully functional MADH by catalyzing the insertion of a second oxygen atom into the indole ring and covalently linking ...
Tryptanthrin originally isolated from Isatis tinctoria L. has been characterized to have anti-inflammatory activities through the dual inhibition of cyclooxygenase-2 and 5-lipoxygenase mediated prostaglandin and leukotriene syntheses. To characterize phase I metabolite(s), tryptanthrin was incubated with rat liver microsomes in the presence of NADPH-generating system. One metabolite was identified ...
Danazol (17alpha-pregna-2,4-dien-20-yno [2,3-d]-isoxazol-17beta-ol), is a synthetic derivative of ethisterone, structurally related to stanozolol. For this reason its use as doping agent has been investigated. Danazol (Runch) (200 mg) were orally administered to two healthy male volunteers. Urine samples were collected up to 1-week post-dose. Four new metabolites have been identified in addition ...
The carbonyl stress that leads to the formation of advanced glycation end products (AGEs) has drawn much attention recently because of its micro- and macrovascular implications. During monitoring of methylglyoxal (MG), the efficiency of phenolics to directly trap MG can be demonstrated. Twenty compounds consisting of a single benzene ring structure with the addition of at least one hydroxyl group ...
One hundred and two basidiomycete strains (93 species in 41 genera) that prefer a soil environment were examined for screening of 1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) biodegradation. Three strains within two litter-decomposing genera, Agrocybe and Marasmiellus, were selected for their DDT biotransformation capacity. Eight metabolites; 1,1-dichloro-2,2-bis(4-chlorophenyl)ethane ...
A new member of class IV of cytochrome P450 monooxygenases was identified in Rhodococcus ruber strain DSM 44319. As the genome of R. ruber has not been sequenced, a P450-like gene fragment was amplified using degenerated primers. The flanking regions of the P450-like DNA fragment were identified by directional genome walking using polymerase chain reaction. The primary protein structure suggests a ...
Rutaecarpine has recently been characterized to have an anti-inflammatory activity through cyclooxygenase-2 inhibition. The incubation of rutaecarpine with human liver microsomes in the presence of NADPH generated six isobaric mono-hydroxylated metabolites. The specific cytochrome P450 (CYP) isozymes responsible for rutaecarpine metabolites were identified using the ...
The role of green microalgae in the biotransformation of naphthalene (a polycyclic aromatic hydrocarbon) and diaryl ethers was investigated using axenic cultures of Chlorella vulgaris and two environmental isolates, Scenedesmus SI1 and Ankistrodesmus SI2. Biotransformation experiments with dense cell cultures showed that these three green algae transformed toxic xenobiotics to more polar ...
The toluene-degrading strain Rhodococcus opacus PWD4 was found to hydroxylate d-limonene exclusively in the 6-position, yielding enantiomerically pure (+) trans-carveol and traces of (+) carvone. This biotransformation was studied using cells cultivated in chemostat culture with toluene as a carbon and energy source. The maximal specific activity of (+) trans-carveol formation was 14.7 U (g of ...
The biodegradation of azaarenes and coal-tar creosote was studied using aerobic bacteria isolated from creosote contaminated soil as inocula in batch cultures and in immobilized cell bioreactors. Biodegradation of quinoline, isoquinoline, and 6-methylquinoline by pure and mixed cultures yielded mono-hydroxylated metabolites as the primary products of azaarene metabolism. All ...
Well-defined amphiphilic block-graft copolymers PCL-b-[DTC-co-(MTC-mPEG)] with polyethylene glycol methyl ether pendant chains were designed and synthesized. First, monohydroxyl-terminated macroinitiators PCL-OH were prepared. Then, ring-opening copolymerization of 2,2-dimethyltrimethylene carbonate (DTC) and cyclic carbonate-terminated PEG (MTC-mPEG) macromonomer was carried ...
The electrostrictive response of small carbon clusters, hydrocarbon molecules, and carbon nanotubes is investigated using the density functional theory. For ringlike carbon clusters, one can get insight on the deformations induced by an electric field from a simple two-dimensional model in which the positive charge of the carbon ions is smeared out in a circular homogeneous line of charge and the ...
Strigolactones are signaling compounds in plants of increasing importance. In this paper the focus is on their activity as germinating agents for seeds of parasitic weeds. The syntheses of aromatic A-ring analogues of the germination stimulant orobanchol have been described. Starting substrate is the ABC unit of the stimulant GR24. Oxidation at the C-4 position gives a 4-oxo ...
A new assay using low-dose electron diffraction to measure the protection of protein structure against damage from drying is described. When thin single crystals of catalase are dried within water alone, low-dose electron diffraction yields no Bragg spots. Drying within an experimental aqueous solution that permits detection of diffraction spots thereby indicates a positive result, and the extent ...
Oxymetazoline (6-tert-butyl-3-(2-imidazolin-2-ylmethyl)-2,4-dimethylphenol) has been widely used as a nonprescription nasal vasoconstrictor for >40 years; however, its metabolic pathway has not been investigated. This study describes the in vitro metabolism of oxymetazoline in human, rat, and rabbit liver postmitochondrial supernatant fraction from homogenized tissue (S9) fractions and their ...
Compomers are a new class of materials. With the compomer Dyract Ortho., specifically for bracket bonding, and with Prime & Bond 2.0, a one-component primer for enamel and dentin, DeTrey/Dentsply has developed alternative new materials. The aim of this in vitro study was to test the tensile bonding strength of these materials with different kinds of ...
Dimethandrolone undecanoate (DMAU: 7?,11?-dimethyl-19-nortestosterone 17?-undecanoate) is a potent orally active androgen in development for hormonal therapy in men. Cleavage of the 17?-ester bond by esterases in vivo leads to liberation of the biologically active androgen, dimethandrolone (DMA), a 19-norandrogen. For hormone replacement in men, administration of C19 androgens such as testosterone ...
Flavobacteriaceae (strain S03) and Cytophaga sp. (strain 41-DBG2) are algicidal bacteria active against the brevetoxin (PbTx)-producing, red tide dinoflagellate, Karenia brevis. Little is known about the fate of PbTx associated with K. brevis cells following attack by such bacteria. The fate and distribution of PbTx in K. brevis cultures exposed to these algicidal strains were thus examined by ...
A-ring phenol (84% yield). Since the latter event was unintended, subsequent treatment with LiOH-TsOH k) TBSCl, imid l) LiOH m) BnBr, KF�alumina n) 9-BBN 10 11 Scheme 2. Synthesis of indole�oxazole 6.0 equiv), imid (6.0 equiv), CH2Cl2, 258C, 6 h, 84%; l) LiOH (3.0 equiv), DMF, 258C, 5 h; m) BnBr (4
A procedure is described for the preparation of A-homo-5-pregnenes via an acid catalyzed rearrangement of cyclopropylcarbinols assisted by microwave irradiation. 3alpha-Hydroxy and 4alpha-hydroxy-A-homo-5-pregnen-20-one, analogues of the neuroactive steroid allopregnanolone, were obtained by means of a regioselective epoxidation of a double bond in the expanded A-ring, using a ...
We have investigated the surface composition of alkali-halide aqueous solutions using grazing incidence x-ray fluorescence. Using mixtures of salts as a means to enhance the short-range effects, small differences in concentration over a few angstrom could be resolved, with, for example I{sup -} or Br{sup -}>Cl{sup -}. In order to explain our data, we need to include an effective potential ...
Three optical monitors image the transverse cross section of the electron beam at BESSY II. The emittance of the electron beam can be determined from source images generated by hard X-ray pinhole cameras without additional measurement of the energy width of the beam. Vertical emittance changes down to 3pmrad can be detected. Typical emittance values of 5
Full details are provided for an improved synthesis of cortistatin A and related structures as well as the underlying logic and evolution of strategy. The highly functionalized cortistatin A-ring embedded with a key heteroadamantane was synthesized by a simple and scalable five-step sequence. A chemoselective, tandem geminal dihalogenation of an unactivated methyl group, a ...
Atomistic molecular dynamics simulation (MDS) was development to investigate the structural and dynamic properties of a monolayer of supramolecular systems. The simulations were performed at room temperature, on inclusion complexes (ICs) of {alpha}-cyclodextrin (CD) with poly(ethylene-oxide)(PEO), poly({epsilon}-caprolactone)(PEC) and poly(tetrahydrofuran)(PTHF). The simulations were carried out ...
We study in detail the role of short-cuts in promoting the emergence of cooperation in a network of agents playing the Prisoner's Dilemma game (PDG). We introduce a model whose topology interpolates between the one-dimensional Euclidean lattice (a ring) and the complete graph by changing the value of one parameter (the probability p of adding a link ...
An experimental setup for the investigation of wear is described. For the elimination of the circulation of oil contaminated with the radioactive products of wearing, a system with two and six G-M tubes was worked out. To eliminate the variation of the area of friction surface, first a fixed radioactive preparation was used, but later a sliding one (a ...
Mutated BRAF serine/threonine kinase is implicated in several types of cancer, with particularly high frequency in melanoma and colorectal carcinoma. We recently reported on the development of BRAF inhibitors based on a tripartite A-B-C system featuring an imidazo[4,5]pyridin-2-one group hinge binder. Here we present the design, synthesis, and optimization of a new series of inhibitors with a ...
Three new flavonoids, oxytropisoflavans A (1) and B (2) and (6aR,11aR)-3,8-dihydroxy-9,10-dimethoxypterocarpan (3), together with 30 known flavonoids (4-33), were isolated from the aerial parts and roots of Oxytropis falcata. The absolute configurations of 3 and C-3 in 1 and 2 were deduced by circular dichroism. The structure of flavonoid 2 was confirmed by single-crystal X-ray diffraction ...
A series of steroid and azasteroid analogues containing a six-membered ring A with various functionalities were synthesized. Furthermore, the syntheses of tetracyclic analogues bearing a five-membered A-ring and the syntheses of a number of bicyclic secosteroid analogues were carried out. All compounds were tested for their antibacterial, antifungal and cytotoxic activities. ...
Phycoerythrocyanin carries two covalently attached phycocyanobilin (PCB) groups on the ..beta.. subunit and a phycobiliviolinoid (PXB) group on the ..cap alpha.. subunit. Three distinct bilipeptides were obtained by proteolytic digestion of this protein: Asn-Gln-Ala-Ala-Cys(PCB)-Ile-Arg, Gly-Asp-Cys(PCB)-Ser-Gln, and Cys(PXB)-Val-Arg. Correlation 500-MHz /sup 1/H NMR analyses showed that the ...
Flavanone glucuronides are the major phenolic metabolites detected in human plasma after consumption of citrus fruits. As such, they might display significant cardioprotective effects. In this work, glucuronides of naringenin (4'- and 7-O-beta-d-glucuronides) and hesperetin (3'- and 7-O-beta-d-glucuronides), the major flavanone aglycones in grapefruit and orange, respectively, have been chemically ...
BackgroundK2 products are synthetic cannabinoid-laced, marijuana-like drugs of abuse, use of which is often associated with clinical symptoms atypical of marijuana use, including hypertension, agitation, hallucinations, psychosis, seizures and panic attacks. JWH-018, a prevalent K2 synthetic cannabinoid, is structurally distinct from ?9-THC, the main psychoactive ingredient ...
In the last decade, several studies have demonstrated that stable isotope tools are highly applicable for monitoring anaerobic biodegradation processes. An important methodological approach is to characterize distinct degradation pathways with respect to the specific mechanism of C-H-bond cleavage and to quantify the extent of biodegradation by compound specific isotope analysis (CSIA). Here, ...
The saprophytic fungus Rhizopus nigricans constitutes a serious problem when thriving on gathered crops. The identification of any compounds, especially natural ones, that inhibit fungal growth, may therefore be important. During its life cycle, Rhizopus nigricans encounters many compounds, among them the flavonoids, plant secondary metabolites that are involved in plant defense against pathogenic ...
Steroid degradation by Comamonas testosteroni and Nocardia restrictus have been intensively studied for the purpose of obtaining materials for steroid drug synthesis. C. testosteroni degrades side chains and converts single/double bonds of certain steroid compounds to produce androsta-1,4-diene 3,17-dione or the derivative. Following 9?-hydroxylation leads to aromatization of the A-ring ...
Anabolic androgenic steroids (AAS) are included in the List of prohibited substances of the World Anti-Doping Agency (WADA) as substances abused to enhance athletic performance. Gas chromatography coupled to mass spectrometry (GC-MS) plays an important role in doping control analyses identifying AAS as their enolized-trimethylsilyl (TMS)-derivatives using the electron ionization (EI) mode. This ...
This study investigated the underlying mechanisms of action for blood lipid lowering effects of citrus flavonoids and their methoxylated analogues (n = 19; dose range: 0-100 ?M) in HepG2 cells. Cholesterol (CH) and triglyceride (TG) syntheses were assessed by measuring the incorporation of (14)C-acetate and (14)C-glycerol, respectively, whereas apoB secretion was determined by ELISA. Results show ...
Structure-activity relationships for the MDM2-p53 inhibitory activity of a series of A-ring substituted 2-N-benzyl-3-(4-chlorophenyl)-3-(1-(hydroxymethyl)cyclopropyl)methoxy)isoindolinones have been investigated, giving rise to compounds with improved potency over their unsubstituted counterparts. Isoindolinone A-ring substitution with a 4-chloro group for the 4-nitrobenzyl, ...
The present preliminary study describes an investigation of a putative aromatisation pathway in sewage from cholesterol through the corresponding A-ring aromatic steroid, norcholest-1,3,5(10)-trienol (NCT) to estrone. The synthesis and analytical characterisation of NCT and of the trimethyl silyl ether by gas chromatography-mass spectrometry, is described. The analytical ...
A transition from petroleum~derived jet fuels to blends with Fischer-Tropsch (F~T) fuels, and ultimately fully synthetic hydro-isomerized F-T fuels has raised concern about the fate of plasticizers in nitrile-butadiene rubber a-rings that are contacted by the fuels as this transition occurs. The partitioning of plasticizers and fuel molecules between nitrile ...
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The estrogen-like effects of norethisterone (NET) seem to be mediated by the interaction of 3 beta 5 alpha- and 3 alpha 5 alpha-tetrahydronorethisterone (3 beta 5 alpha- and 3 alpha 5 alpha-NET, respectively) with the estrogen receptor. Considering that the in vitro uterine contractile response to serotonin (5-HT) is specifically dependent on estrogen, the aim of the present study was to ...
The potentials for in situ biodegradation of 17?-estradiol (E2), estrone (E1), and testosterone (T) were investigated in three, hydrologically-distinct, WWTP-impacted streams in the United States. Relative differences in the mineralization of [4-14C] substrates were assessed in oxic microcosms containing sediment or water-only from locations upstream and downstream of the WWTP outfall in each ...
Burkholderia cenocepacia is a member of the Burkholderia cepacia complex, a group of metabolically versatile bacteria that have emerged as opportunistic pathogens in cystic fibrosis and immunocompromised patients. Previously a screen of transposon mutants in a rat pulmonary infection model identified an attenuated mutant with an insertion in paaE, a gene related to the phenylacetic acid (PA) ...
Polychlorinated biphenyls (PCBs) are among the ubiquitously persistent chemicals possessing endocrine-disrupting effects. Most of the environmentally abundant CB congeners have one or more ortho chlorines in the biphenyl ring. Because ortho-chlorinated CB congeners do not avidly bind to the aryl hydrocarbon (Ah) receptor, this clearly suggests that the estrogenicity of PCBs is not related to ...
The in vitro metabolism of pregnenolone by two Bacillus strains (HA-V6-3 and HA-V6-11) isolated from the foregut of the water beetle Agabus affinis (Payk.) was examined in the course of our studies about a possible participation of gut micro-organisms in the biosynthesis of prothoracic defensive steroids of dytiscids. The transformation products were identified by EI GC--MS of culture extracts ...
Field pennycress (Thlaspi arvense L.) is a winter annual crucifer with a cold requirement for stem elongation and flowering. In the present study, the metabolism of exogenous [(2)H]-ent-kaurenoic acid (KA) and [(14)C]-gibberellin A(12)-aldehyde (GA(12)-aldehyde) was compared in thermo- and noninduced plants. Thermoinduction greatly altered both quantitative and qualitative aspects of [(2)H]-KA ...
The genes encoding the six polypeptide components of the alkene monooxygenase from Xanthobacter strain Py2 (Xamo) have been located on a 4.9-kb fragment of chromosomal DNA previously cloned in cosmid pNY2. Sequencing and analysis of the predicted amino acid sequences indicate that the components of Xamo are homologous to those of the aromatic monooxygenases, toluene 2-, 3-, and 4-monooxygenase and ...
A novel thermoreversible hydrogel based on poly(2-ethyl-2-oxazoline)-derived amphiphilic triblock copolymer, poly(2-ethyl-2-oxazoline)-poly(d,l-lactide)-poly(2-ethyl-2-oxazoline) (PEOz-PLA-PEOz), was developed. The synthesis of PEOz-PLA-PEOz was carried out by coupling monohydroxylated PEOz-PLA diblocks with adipoyl chloride as coupling agent and dimethylamino pyridine as ...
To corroborate the structures of two monohydroxylated metabolites of topiramate (1), we synthesized four monosaccharide derivatives from D-fructose: 4,5-O-[(1R)- and 4,5-O-[(1S)-1-hydroxymethylethylidene]-2,3-O-isopropylidene-beta-D -fructopyranose sulfamates (2a and 2b); 2,3-O-[(1R)- and 2,3-O-[(1R)-1-hydroxymethylethylidene]-4,5-O-isopropylidene-beta-D -fructopyranose ...
Benzene dioxygenase and toluene dioxygenase from Pseudomonas putida have similar catalytic properties, structures, and gene organizations, but they differ in substrate specificity, with toluene dioxygenase having higher activity toward alkylbenzenes. The catalytic iron-sulfur proteins of these enzymes consist of two dissimilar subunits, ? and ?; the ? subunit contains a [2Fe-2S] cluster involved ...
Artemisinin drugs have become the first-line antimalarials in areas of multi-drug resistance. However, monotherapy with artemisinin drugs results in comparatively high recrudescence rates. Autoinduction of CYP-mediated metabolism, resulting in reduced exposure, has been supposed to be the underlying mechanism. To better understand the autoinduction of artemisinin drugs, we evaluated the ...
Bisphenol A (BPA), a controversial endocrine disruptor, is ubiquitous in the aquatic environment. In this study, the oxidative degradation of BPA and its mechanism using zero valent aluminum (ZVAl)-acid system under air-equilibrated conditions was investigated. Under pH <3.5 acidic conditions, ZVAl demonstrated an excellent capacity to remove BPA. More than 75% of BPA was eliminated within 12 h ...
Polychlorinated biphenyls (PCBs) are toxic industrial chemicals, complete carcinogens, and efficacious tumor promoters. However, the mechanism(s) of PCB-mediated carcinogenicity remains largely undefined. One likely pathway by which these agents may play a role in carcinogenesis is the generation of oxidative DNA damage by redox cycling of dihydroxylated PCB metabolites. We have now employed a new ...
The catalytic properties of purified cytochrome P-450b, the major isozyme found in hepatic microsomes from phenobarbital-pretreated rats, for the metabolism of N-methylcarbazole (NMC) were analyzed in two membranous systems in order to investigate membrane bilayer-dependent parameters. Incorporation of the enzymes of the monoxygenase system into bilayer liposomal vesicles composed of total ...
When Streptomyces roseochromogenes strain 10984 was incubated with exogenous progesterone for 25 h the major monohydroxylated metabolite, 16alpha-hydroxyprogesterone was produced in 3.6 fold excess to the minor metabolite 2beta,16alpha-dihydroxyprogesterone. In a reconstituted system containing highly purified progesterone 16alpha-hydroxylase cytochrome P-450, and electron ...
1. A bacterium, Achromobacter D, isolated from garden soil by elective culture, utilized N-methylisonicotinic acid (4-carboxy-1-methylpyridinium chloride) as sole carbon source. 2. Extracts of N-methylisonicotinate-grown cells oxidized this substrate only after supplementation with a source of nicotinamide nucleotides and then consumed 1 mol of O2 and released 1 mol of ...
The metabolism of cyclosporin A (CsA), a widely used immunosuppressive agent, was evaluated in freshly isolated rabbit hepatocytes by HPLC which separated CsA from its major group of derivatives, e.g. first generation metabolites (monohydroxylated and N-demethylated) and second generation derivatives (dihydroxylated and dihydroxy-N-demethylated). After exposure of hepatocytes ...
Triptolide, the primary active component of Tripterygium wilfordii Hook F, has various pharmacological activities but also a narrow therapeutic window. Cytochrome P450s are proposed to be responsible for the hydroxylation of triptolide in vitro and CYP3A induction by dexamethasone can increase the metabolism of triptolide and decrease the hepatotoxicity in rat. However, triptolide-induced toxicity ...
We have investigated the effect of a range of 2-nitroimidazoles on CCNU metabolism, using an in vitro mouse liver microsomal preparation. CCNU is hydroxylated to at least 5 monohydroxylated metabolites. For the major metabolite, cis-4-hydroxy CCNU, values of Km and Vmax were 0.026 mM and 1.92 nmol/min/mg protein, respectively. MISO and other 2-nitroimidazoles inhibited the ...
Several lines of evidence indicate that (+)-?-cadinene-8-hydroxylase (CYP706B1) plays an important role in biosynthesis of gossypol in Gossypium arboreum L. (Luo et al., 2001; Wang et al., 2003). The catalytically active enzyme has been expressed in yeast microsomes. Some microsomal preparations conjugated the hydroxylated (+)-?-cadinene to a moiety that has not yet been identified. However, when ...
The metabolism of aclidinium bromide, a novel long-acting antimuscarinic drug for the maintenance treatment of chronic obstructive pulmonary disorder, has been investigated in liver microsomes and hepatocytes of mice, rats, rabbits, dogs, and humans. Due to the rapid hydrolysis of this ester compound, two distinct radiolabeled forms of aclidinium were studied. The main biotransformation route of ...
Background. Cooking with biomass fuels on open fires results in exposure to health-damaging pollutants such as carbon monoxide (CO), polycyclic aromatic hydrocarbons (PAHs), and particulate matter. Objective. Compare CO exposures and urinary PAHs biomarkers pre- and post-intervention with an improved biomass stove - the Patsari stove. Methods. A sub-sample of 63 women participating in a randomized ...
The objective of this research was the identification of the metabolic profile of fluasterone, a synthetic derivative of dehydroepiandrosterone, in dogs treated orally or subcutaneously with [4-14C]fluasterone. Separation and characterization techniques used to identify the principal metabolites of fluasterone in urine and feces included high-performance liquid ...
Hydroxyatrazine [2-(N-ethylamino)-4-hydroxy-6-(N-isopropylamino)-1,3,5-triazine] N-ethylaminohydrolase (AtzB) is the sole enzyme known to catalyze the hydrolytic conversion of hydroxyatrazine to N-isopropylammelide. AtzB, therefore, serves as the point of intersection of multiple s-triazine biodegradative pathways and is completely essential for microbial growth on s-triazine herbicides. Here, ...
Twenty-nine species (76 strains) of members of the genus Legionella were analyzed for their cellular hydroxylated fatty acids (OH-FAs). The individual patterns were unusually complex and included both monohydroxylated and dihydroxylated chains of unbranched or branched (iso and anteiso) types. Comparison of the strain profiles by SIMCA (Soft Independent Modelling of Class ...
This study investigated if genetic differences exhibited in endophyte-resistant and -susceptible mouse lines had persisted after 13 generations in which the integrity of lines was maintained yet selection ceased. Experimental groups were mouse lines fed an endophyte-free (E-) or -infected (E+) diet. The in vitro metabolism of the ergot alkaloid ergotamine in mouse liver microsomes was ...
While the proteome defines the expressed gene products, the metabolome results from reactions controlled by such gene products. Plasma represents an accessible �window� to the metabolome both in regard of availability and content. The wide range of the plasma metabolome, in terms of molecular diversity and abundance, makes its comprehensive analysis challenging. Here we demonstrate an ...
A method for the determination of a prostaglandin D(2) receptor antagonist (I, a compound being evaluated for the prevention of niacin induced flushing) and its acyl glucuronide metabolite (II) in human plasma is presented. The method utilized high performance liquid chromatography (HPLC) with tandem mass spectrometric (MS/MS) detection using an atmospheric pressure chemical ionization (APCI) ...
An efficient and selective method for the quantitative determination of Polycyclic Aromatic Hydrocarbons (PAHs) and their monohydroxylated metabolites (OH-PAHs) in rat brain tissue using gas chromatography tandem (triple quadrupole) mass spectrometry (GC-MS/MS) was developed and validated. The list of molecules investigated comprised the 16 PAHs from the US-EPA list and 53 of ...
The metabolic transformation of methandienone (I) in the horse was investigated. After administration of a commercial drug preparation to a female horse (0.5 mg/kg), urine samples were collected up to 96 h and processed without enzymic hydrolysis. Extraction was performed by a series of solid-liquid and liquid-liquid extractions, thus avoiding laborious purification techniques. For analysis by gas ...
Ciprofloxacin (CIP), a fluoroquinolone antibacterial drug, is widely used in the treatment of serious infections in humans. Its degradation by basidiomycetous fungi was studied by monitoring 14CO2 production from [14C]CIP in liquid cultures. Sixteen species inhabiting wood, soil, humus, or animal dung produced up to 35% ...
Methylomonas sp. strain 16a is an obligate methanotrophic bacterium that uses methane or methanol as the sole carbon source. An effort was made to engineer this organism for astaxanthin production. Upon expressing the canthaxanthin gene cluster under the control of the native hps promoter in the chromosome, canthaxanthin was produced as the main carotenoid. Further conversion to astaxanthin was ...
Direct oxidation fuel cells using proton-exchange membrane electrolytes have long been recognized as being an attractive mode of power generation. The current work addresses the electro-oxidation characteristics of a number of potential fuels on Pt-based electrodes which can be used in direct oxidation fuel cells, including hydrocarbons and oxygenated molecules, such as alcohols, formates, ethers, ...
Bilinoid pigments in bile of homozygous Gunn rats (jj) were analysed either after formation of dipyrrolic ethyl anthranilate azo derivatives or as the unmodified parent tetrapyrroles. 1. T.l.c. of the azo derivatives revealed seven major unconjugated components which were structurally characterized by chemical tests, spectrophotometry and mass spectrometry. In addition, two minor components were ...
The biotransformation of 17alpha-ethinylestradiol (EE2) by an ammonia oxidizing bacteria, Nitrosomonas europaea, grown in batch (ammonia-rich) and continuous flow (chemostat, ammonia-limited) reactors was investigated. Both C-14 labeled EE2 (10 gammag/L) and unlabeled EE2 (1 mg/L) were used to facilitate metabolite identification under environmentally relevant physiological conditions. Whole cell ...
Selective androgen receptor modulators (SARMs) have great therapeutic potential in various diseases including cancer cachexia, sarcopenia, and osteoporosis, and the number of drug candidates has been growing over the last decade. The SARM drug candidates S-22 and S-23 belong to one of the most advanced groups of androgen receptor modulators and are based on an arylpropionamide-derived core ...
CYP703 is a cytochrome P450 family specific to land plants. Typically, each plant species contains a single CYP703. Arabidopsis thaliana CYP703A2 is expressed in the anthers of developing flowers. Expression is initiated at the tetrad stage and restricted to microspores and to the tapetum cell layer. Arabidopsis CYP703A2 knockout lines showed impaired pollen development and a partial male-sterile ...
We examined the pathway by which the fungicide biphenyl is metabolized in the imperfect fungus Paecilomyces lilacinus. The initial oxidation yielded the three monohydroxylated biphenyls. Further hydroxylation occurred on the first and the second aromatic ring systems, resulting in the formation of five di- and trihydroxylated metabolites. The fungus could cleave the aromatic ...
In our research project entitled "Chemical irritative and/or genotoxic effect of fumes of bitumen under high processing temperatures on the airways," 73 mastic asphalt workers exposed to fumes of bitumen and 49 construction nonexposed workers were analyzed and compared with respect to polycyclic aromatic hydrocarbons (PAHs) exposure and exposure-related health effects. In order to assess the ...
Microorganisms capable of degrading diphenylarsinic acid (DPAA) were enriched from contaminated soil using the soil-charcoal perfusion method. Two novel bacterial strains, L2406 and L2413, that can degrade DPAA in a mineral salt medium supplemented with DPAA as the sole carbon source were isolated. Based on comparative morphology, physiology, and comparison of the 16S rRNA gene sequences, both ...
Bioconversion of various substituted naphthalenes that contain 1-methoxy- and 1-ethoxy-naphthalenes, methylnaphthalenes, dimethylnaphthalenes, and naphthalenecarboxylic acid methyl esters were performed using recombinant Escherichia coli cells, which expressed the gene coding for a cytochrome P450 BM3 variant F87V (P450 BM3 (F87V)) that was N-terminally fused to an archaeal peptidyl-prolyl ...
Selective androgen receptor modulators (SARM) are a prominent group of compounds for being misused in sports owing to their advantageous anabolic properties and reduced side effects. To target the preventive doping control analysis in relevant compounds, the challenge is to predict the metabolic fate of a new compound. For aryl-propionamide-derived SARM, an in vitro assay employing microsomal and ...
Arsenic is a ubiquitous environmental toxic metal. Consequently, organisms detoxify arsenate by reduction to arsenite, which is then excreted or sequestered. The ArsC arsenate reductase from Escherichia coli plasmid R773, the best characterized arsenic-modifying enzyme, has a catalytic cysteine, Cys 12, in the active site, surrounded by an arginine triad composed of Arg 60, Arg 94, and Arg 107. ...
A simple and sensitive method was developed to separate the carcinogenic polycyclic aromatic hydrocarbon (PAH), benzo[a]pyrene (BaP), and six of its oxidation metabolites generated by rat hepatic microsomes enriched with cytochrome P450 (CYP) 1A1, by high pressure liquid chromatography (HPLC). The HPLC method, using an acetonitrile/water gradient as mobile phase and UV detection, provided ...
Aggregatibacter actinomycetemcomitans, a common inhabitant of the human upper aerodigestive tract, produces a repeat in toxin (RTX), leukotoxin (LtxA). The LtxA is transcribed as a 114-kDa inactive protoxin with activation being achieved by attachment of short chain fatty acyl groups to internal lysine residues. Methyl esters of LtxA that were isolated from A. actinomycetemcomitans strains JP2 and ...
1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane (DDT) was used as the substrate for a degradation experiment with the white rot fungi Phlebia lindtneri GB-1027 and Phlebia brevispora TMIC34596, which are capable of degrading polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated biphenyls (PCBs). Pure culture of P. lindtneri and P. brevispora with DDT (25�?mol�l(-1)) showed that 70 and 30% ...
High-valent iron species are powerful oxidizing agents in chemical and biological catalysis. The best characterized form of an Fe(V) equivalent described in biological systems is the combination of a b-type heme with Fe(IV)=O and a porphyrin or amino acid cation radical (termed Compound I). This work describes an alternative natural mechanism to store two oxidizing equivalents above the ferric ...
Poor knowledge of optical constants of various materials in the soft x-ray region requires to test the soft x-ray optical devices at actual wavelengths. For such purposes a soft x-ray/vacuum ultraviolet reflectivity beamline has been setup on Indus-1 synchrotron.X-ray multilayer structures are also being developed at RRCAT. Silicon based different multilayer optics fabricated in house for ...
The carbonyl stress that leads to the formation of advanced glycation end products (AGEs) in diabetes mellitus has drawn much attention recently. Reactive alpha-dicarbonyl compounds, such as glyoxal (GO) and methylglyoxal (MGO), have been shown to be a high potential glycation agent in vitro and in vivo. In this study, epicatechins in green tea and theaflavins in black tea were found to be able to ...
CR (dibenz[b,f]-1,4-oxazepine) is metabolized by rat liver 105 000 g supernatant fractions by (a) ring opening and reduction to 2-amino-2'-hydroxymethyldiphenyl ether and (b) oxidation at C11 to give a cyclic lactam. Reaction (a) is NADPH-dependent, decreased by dialysis and methylene blue, whereas reaction (b) is heat-resistant, inactivated by dialysis, ...
Here we show that Dictyostelium discoideum dynamin A is a fast GTPase, binds to negatively charged lipids, and self-assembles into rings and helices in a nucleotide-dependent manner, similar to human dynamin-1. Chemical modification of two cysteine residues, positioned in the middle domain and GTPase effector domain (GED), leads to altered assembly properties and the stabilization of a highly ...
Summary19-Trideuteromethyl enantiomers of androgens namely ent-testosterone, ent-androsterone and ent-etiocholanolone were prepared by total synthesis. The isotope labeling at the carbon-19 angular methyl group was achieved by using deuterated methyl iodide (99.5% d3) for introduction of C-19 before closure of the steroid A-ring. This method yields ...
Quercetin shows structural features that have been related to the antioxidant potency of flavonoids and also shows neuroprotection in different models of oxidative death. Because only a few studies have focused on the flavonoid structural requirements for neuroprotection, this work evaluated the protective capacity of 13 flavones structurally related to quercetin, isolated from Kenyan plants, to ...
Lipase and amylase inhibitory activities of black tea were examined. After solvent partitioning of a black tea extract with the ethyl acetate and n-butanol, the two soluble fractions showed comparable inhibitory activities. Activity in the ethyl acetate fraction was mainly attributable to polyphenols with low-molecular weights, such as theaflavin gallates. On the other hand, the active substance ...
We synthesized a series of well-defined poly(dl-lactide)-b-poly(N,N-dimethylamino-2-ethyl methacrylate) (PDLLA-b-PDMAEMA) amphiphilic diblock copolymers by employing a three-step procedure: (a) ring-opening polymerization (ROP) of dl-lactide using n-decanol and stannous octoate, Sn(Oct)(2), as the initiating system, (b) reaction of the PDLLA hydroxyl end ...
A purified alkaloid preparation containing N-methylcytisine, cytisine, 5,6-dehydrolupanine, thermopsine and anagyrine from Thermopsis montana induced prolonged recumbency and microscopic acute hyaline skeletal myodegeneration with myofibre regeneration in cattle similar in type and severity to that induced by Thermopsis montanta plant material. This indicates that the alkaloid(s) of Thermopsis ...
Antioxidant action is an important component of the complex neuroprotective action of estrogens. Combining theoretical prediction and subsequent experimental confirmation by chemical and in vitro paradigms, this study focused on the mechanistic aspects of hydroxyl-radical scavenging by 17?-butoxy-1,3,5(10)-estratrien-3-ol, a synthetic derivative of 17?-estradiol with increased potency to inhibit ...
Thermodynamic local-occupation averages and local-number-occupation fluctuations are studied in small-cluster many-body systems by introducing a single-site chemical potential at a particular site. This procedure allows the study of differential properties of thermodynamic functions by providing continuous variation of local occupations. The method, which starts from the quantum-mechanical grand ...
During the summer of 1979, geophysical work was done in the Lassen KGRA in northeastern California to assess the geothermal potential of the area. As part of the study, 68 audio-magnetotelluric (AMT) soundings were made and 2 telluric and self-potential (SP) profiles were done. The AMT station locations are shown. The scalar resistivities were contoured for 7.5 and 27 hertz data at north-south and ...
Novel Kv1.3 blocking immunosuppressants, (-)-candelalides A, B and C, were efficiently synthesized for the first time in a convergent and unified manner starting from (+)-5-methyl-Wieland-Miescher ketone. The synthetic method involved the following key steps: i) a strategic [2,3]-Wittig rearrangement of a stannylmethyl ether to install the stereogenic center at C9 and the exo-methylene function at ...
Imaging and occultation data returned by the two Voyager spacecraft have deepened understanding of dynamical processes operating in Saturn's rings. Saturn's outermost, or A, ring was investigated here in light of this data. Most structure seen in the A ring is caused by spiral density waves, which are regular oscillations in the optical ...
The two-channel nozzle of this spray discharges two separate flows, a mixture of air and dry sealant from a central cylinder, and an encircling spray of water from a concentrically mounted water ring (a ring-shaped manifold). Downstream of the nozzle, the water mixes with the air and sealant to form a wet sealant spray that adheres to mine surfaces with ...
Previously, we reported the discovery of PSI-697 (1a), a C-2 benzyl substituted quinoline salicylic acid-based P-selectin inhibitor. It is active in a variety of animal models of cardiovascular disease. Compound 1a has also been shown to be well tolerated and safe in healthy volunteers at doses of up to 1200 mg in a phase 1 single ascending dose study. However, its oral bioavailability was low. ...
Modern methods for the identification of therapeutic leads include chemical or virtual screening of compound libraries. Nature's library represents a vast and diverse source of leads, often exhibiting exquisite biological activities. However, the advancement of natural product leads into the clinic is often impeded by their scarcity, complexity, and nonoptimal properties or efficacy as well as the ...
An 18 m spherical-grating monochromator with high resolution and high photon flux has been developed at the bending-magnet beamline BL2B2 of the UVSOR facility in the Institute for Molecular Science. The monochromator is designed to cover the energy range 20-200 eV by using three gratings: G1 (2400 lines mm(-1), R = 18 m) at 80-200 eV; G2 (1200 lines mm(-1), R = 18 m) at 40-100 eV; G3 (2400 lines ...
A series of {Delta}{sup 2}-triterpenoids (oleana-2,12-diene, oleana-2,13(18)-diene, oleana-2,18-diene, ursa-2,12-diene, and tarazera-2,14-diene) has been identified in Holocene buried mangrove sediments (Florida, USA) by comparison of the mass spectra of and by co-injections with authentic standards. In the Oligocene Brandon lignite (Vermont, USA) oleana-2,12-diene and oleana-2,13(18)-diene were ...
The immunization procedure and immunogen characteristics required to optimize the production of anti-steroid monoclonal antibodies have been studied. Five different estradiol-bovine serum albumin conjugates were tested for immunizing mice, as were two different immunization protocols (high and low dose) and the effect of varying the myeloma/spleen cell ratio for cell fusion. Antibody-producing ...
Cortisone and hydrocortisone form calcium complexes of 2:1 steroid/Ca(2+) stoichiometry in solution, with formation constants of 201 +/- 1.7 and 184 +/- 1.7 M(-2), respectively-roughly half the value seen for a simple aromatic alpha-hydroxy ketone, phenacyl alcohol (341 +/- 10.0 M(-2)). X-ray crystallographic analysis demonstrates maintenance of this 2:1 stoichiometry in the solid state for the ...
In this study, the atomic layer etching characteristics and the etch mechanism of (100) InP as functions of Cl{sub 2} pressure and Ne neutral beam irradiation dose were investigated. When Cl{sub 2} pressure and Ne neutral beam irradiation dose were lower than the critical values of 0.4 mTorr and 7.2x10{sup 15} at./cm{sup 2} cycle, respectively, the InP etch rate (A ...
During the prototype shop tests, the Model V84.3A ring combustor gas turbine unexpectedly exhibited a noticeable humming caused by self-excited flame vibrations in the combustion chamber for certain operating conditions. The amplitudes of the pressure fluctuations in the combustor were unusually high when compared to the previous experience with silo ...
Chalcones represent a class of natural products that inhibits tubulin assembly. In this study we designed and synthesized boronic acid analogs of chalcones in an effort to compare biological activities with combretastatin A-4, a potent inhibitor of tubulin polymerization. Systematic evaluation of the positional effects of the carbonyl moiety towards inhibition of tubulin polymerization, cancer ...
Density functional theory/B3LYP has been employed to optimize the conformations of selected 4-arylflavan-3-ols and their phenolic methyl ether 3-O-acetates. The electronic circular dichroism spectra of the major conformers have been calculated using time-dependent density functional theory to validate the empirical aromatic quadrant rule applied to the assignment of the absolute configuration of ...
The research objectives and goals of 1983--84 to date include further investigation of 1-halogenated and B-/C-ring halogenated and radio halogenated estradiol derivatives for potential use as receptor-binding radiopharmaceuticals. Our group has devised synthetic routes to 1-bromo, 1-chloro- and 1-fluoroestradiol via electrophilic halogenation of the aromatic A-ring. Work is ...
The time-resolved resonance Raman spectrum of the p-benzosemiquinone radical (HOC/sub 6/H/sub 4/O), excited at 415 nm and observed on the microsecond time scale in the pulse radiolysis of moderately acidic solutions of hydroquinone (pH 2-4), is reported. The nu/sub 7a/ CO stretching mode appears prominently in the spectrum at 1511 cm/sup -1/, showing that the CO bond is very similar to that in ...
Several A-ring-modified analogues of the DNA-binding antitumor agent DC-81 (5) have been synthesized in order to study structure-reactivity/cytotoxicity relationships. For two molecules (23 and 30) the modifications required the addition of a fourth ring to give the novel dioxolo[4,5-h]- and dioxano[5,6-h]pyrrolo[2,1-c][1, 4]benzodiazepin-11-one (PBD) ring systems, ...
MauG is a diheme protein that catalyzes the six-electron oxidation of a biosynthetic precursor protein of methylamine dehydrogenase (PreMADH) with partially synthesized tryptophan tryptophylquinone (TTQ) to yield the mature protein with the functional protein-derived TTQ cofactor. The biosynthetic reaction proceeds via a relatively stable high valent bis-Fe(IV) intermediate. Oxidizing equivalents ...
Fungi, particularly the white rot basidiomycetes, have an extraordinary capability to degrade and/or mineralize (to CO(2)) the recalcitrant fused-ring high molecular weight (4 aromatic-rings) polycyclic aromatic hydrocarbons (HMW PAHs). Despite over 30years of research demonstrating involvement of P450 monooxygenation reactions in fungal metabolism of HMW PAHs, specific P450 monooxygenases ...
