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Sample records for activity ic50 values

  1. Variations in IC(50) values with purity of mushroom tyrosinase.

    PubMed

    Neeley, Elizabeth; Fritch, George; Fuller, Autumn; Wolfe, Jordan; Wright, Jessica; Flurkey, William

    2009-09-01

    The effects of various inhibitors on crude, commercial and partially purified commercial mushroom tyrosinase were examined by comparing IC(50) values. Kojic acid, salicylhydroxamic acid, tropolone, methimazole, and ammonium tetrathiomolybdate had relatively similar IC(50) values for the crude, commercial and partially purified enzyme. 4-Hexylresorcinol seemed to have a somewhat higher IC(50) value using crude extracts, compared to commercial or purified tyrosinase. Some inhibitors (NaCl, esculetin, biphenol, phloridzin) showed variations in IC(50) values between the enzyme samples. In contrast, hydroquinone, lysozyme, Zn(2+), and anisaldehyde showed little or no inhibition in concentration ranges reported to be effective inhibitors. Organic solvents (DMSO and ethanol) had IC(50) values that were similar for some of the tyrosinase samples. Depending of the source of tyrosinase and choice of inhibitor, variations in IC(50) values were observed. PMID:19865520

  2. Variations in IC50 Values with Purity of Mushroom Tyrosinase

    PubMed Central

    Neeley, Elizabeth; Fritch, George; Fuller, Autumn; Wolfe, Jordan; Wright, Jessica; Flurkey, William

    2009-01-01

    The effects of various inhibitors on crude, commercial and partially purified commercial mushroom tyrosinase were examined by comparing IC50 values. Kojic acid, salicylhydroxamic acid, tropolone, methimazole, and ammonium tetrathiomolybdate had relatively similar IC50 values for the crude, commercial and partially purified enzyme. 4-Hexylresorcinol seemed to have a somewhat higher IC50 value using crude extracts, compared to commercial or purified tyrosinase. Some inhibitors (NaCl, esculetin, biphenol, phloridzin) showed variations in IC50 values between the enzyme samples. In contrast, hydroquinone, lysozyme, Zn2+, and anisaldehyde showed little or no inhibition in concentration ranges reported to be effective inhibitors. Organic solvents (DMSO and ethanol) had IC50 values that were similar for some of the tyrosinase samples. Depending of the source of tyrosinase and choice of inhibitor, variations in IC50 values were observed. PMID:19865520

  3. Terpenes Increase the Lipid Dynamics in the Leishmania Plasma Membrane at Concentrations Similar to Their IC50 Values

    PubMed Central

    Camargos, Heverton Silva; Moreira, Rodrigo Alves; Mendanha, Sebastião Antonio; Fernandes, Kelly Souza; Dorta, Miriam Leandro; Alonso, Antonio

    2014-01-01

    Although many terpenes have shown antitumor, antibacterial, antifungal, and antiparasitic activity, the mechanism of action is not well established. Electron paramagnetic resonance (EPR) spectroscopy of the spin-labeled 5-doxyl stearic acid revealed remarkable fluidity increases in the plasma membrane of terpene-treated Leishmania amazonensis promastigotes. For an antiproliferative activity assay using 5×106 parasites/mL, the sesquiterpene nerolidol and the monoterpenes (+)-limonene, α-terpineol and 1,8-cineole inhibited the growth of the parasites with IC50 values of 0.008, 0.549, 0.678 and 4.697 mM, respectively. The IC50 values of these terpenes increased as the parasite concentration used in the cytotoxicity assay increased, and this behavior was examined using a theoretical treatment of the experimental data. Cytotoxicity tests with the same parasite concentration as in the EPR experiments revealed a correlation between the IC50 values of the terpenes and the concentrations at which they altered the membrane fluidity. In addition, the terpenes induced small amounts of cell lysis (4–9%) at their respective IC50 values. For assays with high cell concentrations (2×109 parasites/mL), the incorporation of terpene into the cell membrane was very fast, and the IC50 values observed for 24 h and 5 min-incubation periods were not significantly different. Taken together, these results suggest that terpene cytotoxicity is associated with the attack on the plasma membrane of the parasite. The in vitro cytotoxicity of nerolidol was similar to that of miltefosine, and nerolidol has high hydrophobicity; thus, nerolidol might be used in drug delivery systems, such as lipid nanoparticles to treat leishmaniasis. PMID:25101672

  4. Classification of drug molecules considering their IC50 values using mixed-integer linear programming based hyper-boxes method

    PubMed Central

    Armutlu, Pelin; Ozdemir, Muhittin E; Uney-Yuksektepe, Fadime; Kavakli, I Halil; Turkay, Metin

    2008-01-01

    Background A priori analysis of the activity of drugs on the target protein by computational approaches can be useful in narrowing down drug candidates for further experimental tests. Currently, there are a large number of computational methods that predict the activity of drugs on proteins. In this study, we approach the activity prediction problem as a classification problem and, we aim to improve the classification accuracy by introducing an algorithm that combines partial least squares regression with mixed-integer programming based hyper-boxes classification method, where drug molecules are classified as low active or high active regarding their binding activity (IC50 values) on target proteins. We also aim to determine the most significant molecular descriptors for the drug molecules. Results We first apply our approach by analyzing the activities of widely known inhibitor datasets including Acetylcholinesterase (ACHE), Benzodiazepine Receptor (BZR), Dihydrofolate Reductase (DHFR), Cyclooxygenase-2 (COX-2) with known IC50 values. The results at this stage proved that our approach consistently gives better classification accuracies compared to 63 other reported classification methods such as SVM, Naïve Bayes, where we were able to predict the experimentally determined IC50 values with a worst case accuracy of 96%. To further test applicability of this approach we first created dataset for Cytochrome P450 C17 inhibitors and then predicted their activities with 100% accuracy. Conclusion Our results indicate that this approach can be utilized to predict the inhibitory effects of inhibitors based on their molecular descriptors. This approach will not only enhance drug discovery process, but also save time and resources committed. PMID:18834515

  5. Qualitative assessment of IC50 values of inhibitors of the neuronal nicotinic acetylcholine receptor using a single chromatographic experiment and multivariate cluster analysis.

    PubMed

    Jozwiak, Krzysztof; Moaddel, Ruin; Yamaguchi, Rika; Ravichandran, Sarangan; Collins, Jack R; Wainer, Irving W

    2005-05-01

    It has been widely demonstrated that affinity chromatography can be used to derive binding affinities, and that these affinities can be correlated to data obtained using standard techniques such as membrane binding, ultrafiltration and equilibrium dialysis. The purpose of this study is to evaluate the use of immobilized nicotinic acetylcholine receptor stationary phase in chromatographic experiments to assess the functional activity of series of noncompetitive inhibitors (NCIs) as reflected in their IC50 values. Chromatographically determined retention values and computer generated molecular descriptors were obtained for 29 compounds and the data were analyzed by cluster analysis. The approach qualitatively ranked the test compounds as efficient NCIs (low IC50 values) or poor NCIs (high IC50 values). The data obtained with the 29 compounds used in this study demonstrate that the experimental approach had been able to place 25 of these compounds in the correct IC(50) clusters. To our knowledge, this is the first relationship established between chromatographic retention and IC50 for membrane-bound receptors. These results suggest that the chromatographic approach may be useful in development of lead drug candidates including the determination of off-target binding. PMID:15797535

  6. Single concentration loss of activity assay provides an improved assessment of drug-drug interaction risk compared to IC50-shift.

    PubMed

    Wong, Simon G; Lee, Mey; Wong, Bradley K

    2016-11-01

    1. The utility of two abbreviated, higher-throughput assays [IC50-shift and the loss of activity (LOA) assay] to evaluate time-dependent inhibition (TDI) of 24 structurally related compounds was compared. 2. Good correlation (R(2)  = 0.90) between % inhibition and kinact/KI suggested that the LOA assay has utility as an indicator of TDI potential. Weaker correlation was observed for the shifted IC50 (IC50(T = 30)) (R(2) = 0.61) and the fold-shift in IC50 (R(2) = 0.17). 3. Primary mechanism for poor correlation was depletion of active enzyme at concentrations > 1 μM leading to greater than predicted inhibition in the IC50-shift assay. 4. Previously reported strong correlations between IC50(T = 30) and kinact/KI were found to be dependent on potent TDI compounds with kinact/KI > 30; correlation was reduced for moderate inhibitors (kinact/KI < 30). LOA assay maintained good correlation even when strong TDI compounds were excluded. 5. LOA assay (% Inhibition at 30 min, 10 μM) was a good predictor of in vivo DDI (AUCr), providing a graded response with low potential for false negatives or positives. IC50-shift assay had bias for over-predicting in vivo DDI and was more likely to identify false positives. PMID:26956546

  7. Neuronal in vitro activity is more sensitive to valproate than intracellular ATP: Considerations on conversion problems of IC50 in vitro data for animal replacement.

    PubMed

    Nissen, Matthias; Buehler, Sebastian M; Stubbe, Marco; Gimsa, Jan

    2016-06-01

    We investigated the effects of acute valproate (VPA) on mouse embryonic primary cortex cells (MEPCs). Intracellular ATP concentrations were compared with changes in the mean action potential (AP) frequencies of MEPC networks growing on microelectrode arrays. Our data implies biphasic reactions towards increasing VPA concentrations for both parameters. Intracellular ATP and mean AP frequencies increased around characteristic concentrations of 0.15 and 0.07mM to hormetic plateaus of approx. 120% and 160% of their controls, before fading around 17 and 1.7 mM, respectively. The biphasic in vitro behavior of the two parameters hinders a simple extraction of IC50 and Hillslope values. Different ways of data-fitting with single and double logistic functions are discussed. For a typical hormetic increase of 60% above control, IC50 and Hillslope were decreased by 37% and 15%, respectively. Despite these marginal effects at a logarithmic concentration scale, the hormetic and double logistic behavior of parameters may provide information on the mode of action of toxic compounds. Comparison of our values with the LD50 of mice, recalculated by normalization to body mass, suggests that a neurotoxic rather than a cytotoxic mechanism is killing the animals. The future use of cellular microsystems to replace animal experiments will motivate the development of new microsensors, as well as the consideration of newly accessible parameters in systems biology models. PMID:27091084

  8. Development of Quantum Chemical Method to Calculate Half Maximal Inhibitory Concentration (IC50 ).

    PubMed

    Bag, Arijit; Ghorai, Pradip Kr

    2016-05-01

    Till date theoretical calculation of the half maximal inhibitory concentration (IC50 ) of a compound is based on different Quantitative Structure Activity Relationship (QSAR) models which are empirical methods. By using the Cheng-Prusoff equation it may be possible to compute IC50 , but this will be computationally very expensive as it requires explicit calculation of binding free energy of an inhibitor with respective protein or enzyme. In this article, for the first time we report an ab initio method to compute IC50 of a compound based only on the inhibitor itself where the effect of the protein is reflected through a proportionality constant. By using basic enzyme inhibition kinetics and thermodynamic relations, we derive an expression of IC50 in terms of hydrophobicity, electric dipole moment (μ) and reactivity descriptor (ω) of an inhibitor. We implement this theory to compute IC50 of 15 HIV-1 capsid inhibitors and compared them with experimental results and available other QASR based empirical results. Calculated values using our method are in very good agreement with the experimental values compared to the values calculated using other methods. PMID:27492086

  9. A novel application of t-statistics to objectively assess the quality of IC50 fits for P-glycoprotein and other transporters.

    PubMed

    O'Connor, Michael; Lee, Caroline; Ellens, Harma; Bentz, Joe

    2015-02-01

    Current USFDA and EMA guidance for drug transporter interactions is dependent on IC50 measurements as these are utilized in determining whether a clinical interaction study is warranted. It is therefore important not only to standardize transport inhibition assay systems but also to develop uniform statistical criteria with associated probability statements for generation of robust IC50 values, which can be easily adopted across the industry. The current work provides a quantitative examination of critical factors affecting the quality of IC50 fits for P-gp inhibition through simulations of perfect data with randomly added error as commonly observed in the large data set collected by the P-gp IC50 initiative. The types of errors simulated were (1) variability in replicate measures of transport activity; (2) transformations of error-contaminated transport activity data prior to IC50 fitting (such as performed when determining an IC50 for inhibition of P-gp based on efflux ratio); and (3) the lack of well defined "no inhibition" and "complete inhibition" plateaus. The effect of the algorithm used in fitting the inhibition curve (e.g., two or three parameter fits) was also investigated. These simulations provide strong quantitative support for the recommendations provided in Bentz et al. (2013) for the determination of IC50 values for P-gp and demonstrate the adverse effect of data transformation prior to fitting. Furthermore, the simulations validate uniform statistical criteria for robust IC50 fits in general, which can be easily implemented across the industry. A calibration of the t-statistic is provided through calculation of confidence intervals associated with the t-statistic. PMID:25692007

  10. Determining the IC50 Values for Vorozole and Letrozole, on a Series of Human Liver Cytochrome P450s, to Help Determine the Binding Site of Vorozole in the Liver

    PubMed Central

    Raymond, Lendelle; Rayani, Nikita; Polson, Grace; Sikorski, Kylie; Lian, Ailin; VanAlstine-Parris, Melissa A.

    2015-01-01

    Vorozole and letrozole are third-generation aromatase (cytochrome P450 19A1) inhibitors. [11C]-Vorozole can be used as a radiotracer for aromatase in living animals but when administered by IV, it collects in the liver. Pretreatment with letrozole does not affect the binding of vorozole in the liver. In search of finding the protein responsible for the accumulation of vorozole in the liver, fluorometric high-throughput screening assays were used to test the inhibitory capability of vorozole and letrozole on a series of liver cytochrome P450s (CYP1A1, CYP1A2, CYP2A6, and CYP3A4). It was determined that vorozole is a potent inhibitor of CYP1A1 (IC50 = 0.469 μM) and a moderate inhibitor of CYP2A6 and CYP3A4 (IC50 = 24.4 and 98.1 μM, resp.). Letrozole is only a moderate inhibitor of CYP1A1 and CYP2A6 (IC50 = 69.8 and 106 μM) and a very weak inhibitor of CYP3A4 (<10% inhibition at 1 mM). Since CYP3A4 makes up the majority of the CYP content found in the human liver, and vorozole inhibits it moderately well but letrozole does not, CYP3A4 is a good candidate for the protein that [11C]-vorozole is binding to in the liver. PMID:26635974

  11. Efavirenz concentrations in CSF exceed IC50 for wild-type HIV

    PubMed Central

    Best, Brookie M.; Koopmans, Peter P.; Letendre, Scott L.; Capparelli, Edmund V.; Rossi, Steven S.; Clifford, David B.; Collier, Ann C.; Gelman, Benjamin B.; Mbeo, Gilbert; McCutchan, J. Allen; Simpson, David M.; Haubrich, Richard; Ellis, Ronald; Grant, Igor; Grant, Igor; McCutchan, J. Allen; Ellis, Ronald J.; Marcotte, Thomas D.; Franklin, Donald; Ellis, Ronald J.; McCutchan, J. Allen; Alexander, Terry; Letendre, Scott; Capparelli, Edmund; Heaton, Robert K.; Atkinson, J. Hampton; Woods, Steven Paul; Dawson, Matthew; Wong, Joseph K.; Fennema-Notestine, Christine; Taylor, Michael J.; Theilmann, Rebecca; Gamst, Anthony C.; Cushman, Clint; Abramson, Ian; Vaida, Florin; Marcotte, Thomas D.; von Jaeger, Rodney; McArthur, Justin; Smith, Mary; Morgello, Susan; Simpson, David; Mintz, Letty; McCutchan, J. Allen; Toperoff, Will; Collier, Ann; Marra, Christina; Jones, Trudy; Gelman, Benjamin; Head, Eleanor; Clifford, David; Al-Lozi, Muhammad; Teshome, Mengesha

    2011-01-01

    Objectives HIV-associated neurocognitive disorders remain common despite use of potent antiretroviral therapy (ART). Ongoing viral replication due to poor distribution of antivirals into the CNS may increase risk for HIV-associated neurocognitive disorders. This study's objective was to determine penetration of a commonly prescribed antiretroviral drug, efavirenz, into CSF. Methods CHARTER is an ongoing, North American, multicentre, observational study to determine the effects of ART on HIV-associated neurological disease. Single random plasma and CSF samples were drawn within 1 h of each other from subjects taking efavirenz between September 2003 and July 2007. Samples were assayed by HPLC or HPLC/mass spectrometry with detection limits of 39 ng/mL (plasma) and <0.1 ng/mL (CSF). Results Eighty participants (age 44 ± 8 years; 79 ± 15 kg; 20 females) had samples drawn 12.5 ± 5.4 h post-dose. The median efavirenz concentrations after a median of 7 months [interquartile range (IQR) 2–17] of therapy were 2145 ng/mL in plasma (IQR 1384–4423) and 13.9 ng/mL in CSF (IQR 4.1–21.2). The CSF/plasma concentration ratio from paired samples drawn within 1 h of each other was 0.005 (IQR 0.0026–0.0076; n = 69). The CSF/IC50 ratio was 26 (IQR 8–41) using the published IC50 for wild-type HIV (0.51 ng/mL). Two CSF samples had concentrations below the efavirenz IC50 for wild-type HIV. Conclusions Efavirenz concentrations in the CSF are only 0.5% of plasma concentrations but exceed the wild-type IC50 in nearly all individuals. Since CSF drug concentrations reflect those in brain interstitial fluids, efavirenz reaches therapeutic concentrations in brain tissue. PMID:21098541

  12. Antimicrobial and antileishmanial activities of diterpenoids isolated from the roots of Salvia deserta

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Four diterpenes with biological activity were isolated from Salvia deserta roots. Taxodione was considered leishmanicidal, with IC50 value of 0.46 µg/mL against Leishimania donovani and also exhibited antifungal and antimicrobial activities. Ferruginol displayed the greatest activity (24-h IC50 1.29...

  13. Determining the size and concentration dependence of gold nanoparticles in vitro cytotoxicity (IC50) test using WST-1 assay

    NASA Astrophysics Data System (ADS)

    Rosli, Nur Shafawati binti; Rahman, Azhar Abdul; Aziz, Azlan Abdul; Shamsuddin, Shaharum

    2015-04-01

    Gold nanoparticles (AuNPs) received a great deal of attention for biomedical applications, especially in diagnostic imaging and therapeutics. Even though AuNPs have potential benefits in biomedical applications, the impact of AuNPs on human and environmental health still remains unclear. The use of AuNPs which is a high-atomic-number materials, provide advantages in terms of radiation dose enhancement. However, before this can become a clinical reality, cytotoxicity of the AuNPs has to be carefully evaluated. Cytotoxicity test is a rapid, standardized test that is very sensitive to determine whether the nanoparticles produced are harmful or benign on cellular components. In this work the size and concentration dependence of AuNPs cytotoxicity in breast cancer cell lines (MCF-7) are tested by using WST-1 assay. The sizes of AuNPs tested were 13 nm, 50 nm, and 70 nm. The cells were seeded in the 96-well plate and were treated with different concentrations of AuNPs by serial dilution for each size of AuNPs. The high concentration of AuNPs exhibit lower cell viability compared to low concentration of AuNPs. We quantified the toxicity of AuNPs in MCF-7 cell lines by determining the IC50 values in WST-1 assays. The IC50 values (inhibitory concentrations that effected 50% growth inhibition) of 50 nm AuNPs is lower than 13 nm and 70 nm AuNPs. Mean that, 50nm AuNPs are more toxic to the MCF-7 cells compared to smaller and larger sizes AuNPs. The presented results clearly indicate that the cytotoxicity of AuNPs depend not only on the concentration, but also the size of the nanoparticles.

  14. AutoShim: empirically corrected scoring functions for quantitative docking with a crystal structure and IC50 training data.

    PubMed

    Martin, Eric J; Sullivan, David C

    2008-04-01

    It has been notoriously difficult to develop general all-purpose scoring functions for high-throughput docking that correlate with measured binding affinity. As a practical alternative, AutoShim uses the program Magnet to add point-pharmacophore like "shims" to the binding site of each protein target. The pharmacophore shims are weighted by partial least-squares (PLS) regression, adjusting the all-purpose scoring function to reproduce IC 50 data, much as the shims in an NMR magnet are weighted to optimize the field for a better spectrum. This dramatically improves the affinity predictions on 25% of the compounds held out at random. An iterative procedure chooses the best pose during the process of shim parametrization. This method reproducibly converges to a consistent solution, regardless of starting pose, in just 2-4 iterations, so these robust models do not overtrain. Sets of complex multifeature shims, generated by a recursive partitioning method, give the best activity predictions, but these are difficult to interpret when designing new compounds. Sets of simpler single-point pharmacophores still predict affinity reasonably well and clearly indicate the molecular interactions producing effective binding. The pharmacophore requirements are very reproducible, irrespective of the compound sets used for parametrization, lending confidence to the predictions and interpretations. The automated procedure does require a training set of experimental compounds but otherwise adds little extra time over conventional docking. PMID:18380449

  15. Dual Incorporation of the in vitro Data (IC50) and in vivo (Cmax) Data for the Prediction of Area Under the Curve (AUC) for Statins using Regression Models Developed for Either Pravastatin or Simvastatin.

    PubMed

    Srinivas, N R

    2016-08-01

    Linear regression models utilizing a single time point (Cmax) has been reported for pravastatin and simvastatin. A new model was developed for the prediction of AUC of statins that utilized the slopes of the above 2 models, with pharmacokinetic (Cmax) and a pharmacodynamic (IC50 value) components for the statins. The prediction of AUCs for various statins (pravastatin, atorvastatin, simvastatin and rosuvastatin) was carried out using the newly developed dual pharmacokinetic and pharmacodynamic model. Generally, the AUC predictions were contained within 0.5 to 2-fold difference of the observed AUC suggesting utility of the new models. The root mean square error predictions were<45% for the 2 models. On the basis of the present work, it is feasible to utilize both pharmacokinetic (Cmax) and pharmacodynamic (IC50) data for effectively predicting the AUC for statins. Such a new concept as described in the work may have utility in both drug discovery and development stages. PMID:27144659

  16. Structural modification of 5,7-dimethoxyflavone from Kaempferia parviflora and biological activities.

    PubMed

    Yenjai, Chavi; Wanich, Suchana; Pitchuanchom, Siripit; Sripanidkulchai, Bungon

    2009-09-01

    5,7-Dimethoxyflavone, a major compound from Kaempferia parviflora, was used as a starting material for structural modification. Seven flavonoid derivatives have been synthesized from this flavone. Two new oxime derivatives 4 and 6 exhibited cytotoxicity against HepG2 cell line with IC50 values of 36.38 and 25.34 microg/mL, respectively, and against T47D cell line with IC50 values of 41.66 and 22.94 microg/mL, respectively. Compound 7 showed cytotoxicity against HepG2 and T47D cell lines with IC50 values of 21.36 and 25.00 microg/mL, respectively. Compounds 6 and 7 showed cytotoxicity nearly equal to the tamoxifen standard. In addition, oxime 6 exhibited antifungal activity against Candida albicans with an IC50 value of 48.98 microg/mL. PMID:19784571

  17. Effect of essential oils, such as raspberry ketone and its derivatives, on antiandrogenic activity based on in vitro reporter gene assay.

    PubMed

    Ogawa, Yoshihisa; Akamatsu, Miki; Hotta, Yudai; Hosoda, Akifumi; Tamura, Hiroto

    2010-04-01

    The effect of essential oils, such as raspberry ketone, on androgen (AR) receptor was investigated using a MDA-kb2 human breast cancer cell line for predicting potential AR activity. Among them, eugenol had the highest AR antagonistic activity with its IC(50) value of 19 microM. Raspberry ketone, which has threefold higher anti-obese activity than that of capsaicin, also had AR antagonist activity with its IC(50) value of 252 microM. Based on these findings, a more precise CoMFA model was proposed as follows: pIC(50) [log (1/IC(50))]=3.77+[CoMFA field terms] (n=39, s=0.249, r(2)=0.834, s(cv)=0.507, q(2)=0.311 (three components). PMID:20226658

  18. D-Glucose-Derived 1,2,4-Trioxepanes: Synthesis, Conformational Study, and Antimalarial Activity.

    PubMed

    Sonawane, D P; Corbett, Y; Dhavale, D D; Taramelli, D; Trombini, C; Quintavalla, A; Lombardo, M

    2015-08-21

    New enantiomerically pure 1,2,4-trioxepanes 10a,b/11a,b were synthesized from D-glucose. Their conformational behavior was studied by low-temperature NMR and substantiated by DFT calculations. On evaluation of in vitro antimalarial activity, the adamantyl derivative 11b showed IC50 values in the low micromolar range, particularly against the W2 chloroquine-resistant Plasmodium falciparum strain (IC50 = 0.15 ± 0.12 μM). PMID:26237035

  19. Antiplasmodial Activity of Aporphine Alkaloids and Sesquiterpene Lactones from Liriodendron tulipifera L

    PubMed Central

    Graziose, Rocky; Rathinasabapathy, Thirumurugan; Lategan, Carmen; Poulev, Alexander; Smith, Peter J; Grace, Mary; Lila, Mary Ann; Raskin, Ilya

    2010-01-01

    Aim of the study The objective of this study was to isolate and characterize the active constituents of the traditionally used antimalarial plant Liriodendron tulipifera by antiplasmodial-assay guided fractionation. Materials and methods Bark and leaves were extracted with solvents of increasing polarity. Fractions were generated using flash chromatography, counter current chromatography and preparative HPLC and subjected to in vitro antiplasmodial and cytotoxicity assays. Active fractions were subjected to further fractionation until pure compounds were isolated, for which the IC50 values were calculated. Results and discussion Six known aporphine alkaloids, asimilobine (1), norushinsunine (2), norglaucine (3), liriodenine (4), anonaine (5) and oxoglaucine (6) were found to be responsible for the antiplasmodial activity of the bark. Leaves yielded two known sesquiterpene lactones, peroxyferolide (7) and lipiferolide (8) with antiplasmodial activity. The antiplasmodial activity of (2) (IC50 = 29.6 μg/ml), (3) (IC50 = 22.0 μg/ml), (6) (IC50= 9.1 μg/mL), (7) (IC50 = 6.2 μg/ml) and (8) (IC50 = 1.8 μg/ml) are reported for the first time. Conclusion This work supports the historical use of Liriodendron tulipifera as an antimalarial remedy of the United States and characterizes its antiplasmodial constituents. PMID:20826204

  20. Synthesis of a series of novel dihydroartemisinin monomers and dimers containing chalcone as a linker and their anticancer activity.

    PubMed

    Gaur, Rashmi; Pathania, Anup Singh; Malik, Fayaz Ahmad; Bhakuni, Rajendra Singh; Verma, Ram Kishor

    2016-10-21

    A new series of monomer and dimer derivatives of dihydroartemisinin (DHA) containing substituted chalcones as a linker were synthesized and investigated for their cytotoxicity in human cancer cell lines HL-60 (leukemia), Mia PaCa-2 (pancreatic cancer), PC-3 (prostate cancer), LS180 (colon cancer) and HEPG2 (hepatocellular carcinoma). Some of these derivatives have greater antiproliferative and cytotoxic effects in tested cell lines than parent compound DHA. The structures of the all compounds were confirmed by IR, (1)H NMR and mass spectral data. Among the new derivatives, compounds 8, 14, 15, 20 and 24 were found to be more active than parent DHA against tested human cancer cell lines. DHA derivatives were found to be most active in human leukemia cell lines with compounds 8, 14, 15, 20 and 24 showed IC50 values less than 1 μM for 48 h whereas DHA has IC50 value of 2 μM at same time period. The most potent compounds 8 with IC50 = 0.3 μM (at par with doxorubicin (IC50 = 0.3 μM)) and 15 with IC50 = 0.4 μM, of the series, six and three times active than DHA (with IC50 = 2 μM) respectively were selected for further mechanistic work in human leukemia HL-60 cells. PMID:27371926

  1. Antimalarial activity of anthothecol derived from Khaya anthotheca (Meliaceae).

    PubMed

    Lee, Sung-Eun; Kim, Mi-Ran; Kim, Jeong-Han; Takeoka, Gary R; Kim, Tae-Wan; Park, Byeoung-Soo

    2008-06-01

    Antimalarial activity of anthothecol, a limonoid of Khaya anthotheca (Meliaceae) against Plasmodium falciparum was tested using a [(3)H]-hypoxanthine and 48h culture assay in vitro. Anthotechol showed potent antimalarial activity against malaria parasites with IC(50) values of 1.4 and 0.17microM using two different assays. Also, gedunin had antimalarial activity with IC(50) values of 3.1 and 0.14microM. However, the citrus limonoids, limonin and obacunone did not show any antimalarial activity. The antimalarial activities were compared with the three currently used antimalarial medicines quinine, chloroquinine and artemisinin. PMID:17913482

  2. Evaluation of Antileishmanial Activity of Selected Brazilian Plants and Identification of the Active Principles

    PubMed Central

    Filho, Valdir Cechinel; Meyre-Silva, Christiane; Niero, Rivaldo; Bolda Mariano, Luisa Nathália; Gomes do Nascimento, Fabiana; Vicente Farias, Ingrid; Gazoni, Vanessa Fátima; dos Santos Silva, Bruna; Giménez, Alberto; Gutierrez-Yapu, David; Salamanca, Efrain; Malheiros, Angela

    2013-01-01

    This study evaluated extracts, fractions, and isolated compounds from some selected Brazilian medicinal plants against strains of promastigotes of Leishmania amazonensis and L. brasiliensis in vitro. The cell viability was determined, comparing the results with reference standards. The dichloromethane fractions of the roots, stems, and leaves of Allamanda schottii showed IC50 values between 14.0 and 2.0 μg/mL. Plumericin was the main active compound, with IC50 of 0.3 and 0.04 μg/mL against the two species of Leishmania analyzed. The hexane extract of Eugenia umbelliflora fruits showed IC50 of 14.3 and 5.7 μg/mL against L. amazonensis and L. brasiliensis, respectively. The methanolic extracts of the seeds of Garcinia achachairu and guttiferone A presented IC50 values of 35.9 and 10.4 μg/mL, against L. amazonensis, respectively. The ethanolic extracts of the stem barks of Rapanea ferruginea and the isolated compound, myrsinoic acid B, presented activity against L. brasiliensis with IC50 of 24.1 and 6.1 μg/mL. Chloroform fraction of Solanum sisymbriifolium exhibited IC50 of 33.8 and 20.5 μg/mL, and cilistol A was the main active principle, with IC50 of 6.6 and 3.1 μg/mL against L. amazonensis and L. brasiliensis, respectively. It is concluded that the analyzed plants are promising as new and effective antiparasitic agents. PMID:23840252

  3. Evaluation of antileishmanial activity of selected brazilian plants and identification of the active principles.

    PubMed

    Filho, Valdir Cechinel; Meyre-Silva, Christiane; Niero, Rivaldo; Bolda Mariano, Luisa Nathália; Gomes do Nascimento, Fabiana; Vicente Farias, Ingrid; Gazoni, Vanessa Fátima; Dos Santos Silva, Bruna; Giménez, Alberto; Gutierrez-Yapu, David; Salamanca, Efrain; Malheiros, Angela

    2013-01-01

    This study evaluated extracts, fractions, and isolated compounds from some selected Brazilian medicinal plants against strains of promastigotes of Leishmania amazonensis and L. brasiliensis in vitro. The cell viability was determined, comparing the results with reference standards. The dichloromethane fractions of the roots, stems, and leaves of Allamanda schottii showed IC50 values between 14.0 and 2.0  μ g/mL. Plumericin was the main active compound, with IC50 of 0.3 and 0.04  μ g/mL against the two species of Leishmania analyzed. The hexane extract of Eugenia umbelliflora fruits showed IC50 of 14.3 and 5.7  μ g/mL against L. amazonensis and L. brasiliensis, respectively. The methanolic extracts of the seeds of Garcinia achachairu and guttiferone A presented IC50 values of 35.9 and 10.4  μ g/mL, against L. amazonensis, respectively. The ethanolic extracts of the stem barks of Rapanea ferruginea and the isolated compound, myrsinoic acid B, presented activity against L. brasiliensis with IC50 of 24.1 and 6.1  μ g/mL. Chloroform fraction of Solanum sisymbriifolium exhibited IC50 of 33.8 and 20.5  μ g/mL, and cilistol A was the main active principle, with IC50 of 6.6 and 3.1  μ g/mL against L. amazonensis and L. brasiliensis, respectively. It is concluded that the analyzed plants are promising as new and effective antiparasitic agents. PMID:23840252

  4. Antileishmanial activity of novel indolyl-coumarin hybrids: Design, synthesis, biological evaluation, molecular docking study and in silico ADME prediction.

    PubMed

    Sangshetti, Jaiprakash N; Khan, Firoz A Kalam; Kulkarni, Abhishek A; Patil, Rajendra H; Pachpinde, Amol M; Lohar, Kishan S; Shinde, Devanand B

    2016-02-01

    In present work we have designed and synthesized total twelve novel 3-(3-(1H-indol-3-yl)-3-phenylpropanoyl)-4-hydroxy-2H-chromen-2-one derivatives 13(a-l) using Ho(3+) doped CoFe2O4 nanoparticles as catalyst and evaluated for their potential antileishmanial and antioxidant activities. The compounds 13a, 13d and 13h were found to possess significant antileishmanial activity (IC50 value=95.50, 95.00 and 99.00μg/mL, respectively) when compared to the standard sodium stibogluconate (IC50=490.00 μg/mL). The compounds 13a (IC50=12.40 μg/mL), 13d (IC50=13.49 μg/mL), 13g (IC50=13.24 μg/mL) and 13l (IC50=13.74 μg/mL) had shown good antioxidant activity when compared with standards butylated hydroxy toluene (IC50=16.5 μg/mL) and ascorbic acid (IC50=12.8 μg/mL). After performing molecular docking studies, it was found that compounds 13a and 13d had potential to inhibit pteridine reductase 1 enzyme. In silico ADME pharmacokinetic parameters had shown promising results and none of the synthesized compounds had violated Lipinski's rule of five. Thus, suggesting that compounds from the present series can serve as important gateway for the design and development of new antileishmanial as well as antioxidant agent. PMID:26778149

  5. Antiparasitic activity of some New Caledonian medicinal plants.

    PubMed

    Desrivot, Julie; Waikedre, Jean; Cabalion, Pierre; Herrenknecht, Christine; Bories, Christian; Hocquemiller, Reynald; Fournet, Alain

    2007-05-30

    Twenty-nine extracts of 18 medicinal plants used in New Caledonia by traditional healers to treat inflammation, fever and in cicatrizing remedies were evaluated in vitro against several parasites (Leishmania donovani, Trypanosoma brucei brucei, Trichomonas vaginalis and Caenorhabditis elegans). Among the selected plants, Scaevola balansae and Premna serratifolia L. were the most active against Leishmania donovani with IC(50) values between 5 and 10microg/ml. The almond and aril extracts from Myristica fatua had an IC(50) value of 0.5-5microg/ml against Trypanosoma brucei brucei. Only Scaevola balansae extract presented a weak activity against Trichomonas vaginalis. The almond extract from Myristica fatua presented significant activity against Caenorhabditis elegans (IC(50) value of 6.6+/-1.2microg/ml). PMID:17329051

  6. Anti-elastase and anti-hyaluronidase activities of saponins and sapogenins from Hedera helix, Aesculus hippocastanum, and Ruscus aculeatus: factors contributing to their efficacy in the treatment of venous insufficiency.

    PubMed

    Facino, R M; Carini, M; Stefani, R; Aldini, G; Saibene, L

    1995-10-01

    Triterpene and steroid saponins and sapogenins of medicinal plants (Aesculus hippocastanum L., Hedera helix L., Ruscus aculeatus L.) are claimed to be effective for the treatment/prevention of venous insufficiency. In this work we evaluated the inhibitory effects of these plant constituents on the activity of elastase and hyaluronidase, the enzyme systems involved in the turnover of the main components of the perivascular amorphous substance. The results evidence that for Hedera helix L., the sapogenins only non-competitively inhibit hyaluronidase activity in a dose-dependent fashion, showing comparable IC50 values (hederagenin IC50 = 280.4 microM; oleanolic acid IC50 = 300.2 microM); both the saponins hederacoside C and alpha-hederin are very weak inhibitors. The same behaviour is observed for serine protease porcine pancreatic elastase: the glycosides are devoid of inhibitory action, while genins are potent competitive inhibitors (oleanolic acid IC50 = 5.1 microM; hederagenin IC50 = 40.6 microM). Constituents from Aesculus hippocastanum L. show inhibitory effects only on hyaluronidase, and this activity is mainly linked to the saponin escin (IC50 = 149.9 microM), less to its genin escinol (IC50 = 1.65 mM). By contrast, ruscogenins from Ruscus aculeatus L., ineffective on hyaluronidase activity, exhibit remarkable anti-elastase activity (IC50 = 119.9 microM; competitive inhibition). The mechanism of elastase inhibition by triterpene and steroid aglycones, with a nitroanilide derivative as substrate, is discussed. PMID:8554461

  7. Antiproliferative activity of xanthones isolated from Artocarpus obtusus.

    PubMed

    Hashim, Najihah Mohd; Rahmani, Mawardi; Ee, Gwendoline Cheng Lian; Sukari, Mohd Aspollah; Yahayu, Maizatulakmal; Oktima, Winda; Ali, Abd Manaf; Go, Rusea

    2012-01-01

    An investigation of the chemical constituents in Artocarpus obtusus species led to the isolation of three new xanthones, pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2), and pyranocycloartobiloxanthone B (3). The compounds were subjected to antiproliferative assay against human promyelocytic leukemia (HL60), human chronic myeloid leukemia (K562), and human estrogen receptor (ER+) positive breast cancer (MCF7) cell lines. Pyranocycloartobiloxanthone A (1) consistently showed strong cytotoxic activity against the three cell lines compared to the other two with IC(50) values of 0.5, 2.0 and 5.0 μg/mL, respectively. Compound (1) was also observed to exert antiproliferative activity and apoptotic promoter towards HL60 and MCF7 cell lines at respective IC(50) values. The compound (1) was not toxic towards normal cell lines human nontumorigenic breast cell line (MCF10A) and human peripheral blood mononuclear cells (PBMCs) with IC(50) values of more than 30 μg/mL. PMID:21960741

  8. Active inference and epistemic value.

    PubMed

    Friston, Karl; Rigoli, Francesco; Ognibene, Dimitri; Mathys, Christoph; Fitzgerald, Thomas; Pezzulo, Giovanni

    2015-01-01

    We offer a formal treatment of choice behavior based on the premise that agents minimize the expected free energy of future outcomes. Crucially, the negative free energy or quality of a policy can be decomposed into extrinsic and epistemic (or intrinsic) value. Minimizing expected free energy is therefore equivalent to maximizing extrinsic value or expected utility (defined in terms of prior preferences or goals), while maximizing information gain or intrinsic value (or reducing uncertainty about the causes of valuable outcomes). The resulting scheme resolves the exploration-exploitation dilemma: Epistemic value is maximized until there is no further information gain, after which exploitation is assured through maximization of extrinsic value. This is formally consistent with the Infomax principle, generalizing formulations of active vision based upon salience (Bayesian surprise) and optimal decisions based on expected utility and risk-sensitive (Kullback-Leibler) control. Furthermore, as with previous active inference formulations of discrete (Markovian) problems, ad hoc softmax parameters become the expected (Bayes-optimal) precision of beliefs about, or confidence in, policies. This article focuses on the basic theory, illustrating the ideas with simulations. A key aspect of these simulations is the similarity between precision updates and dopaminergic discharges observed in conditioning paradigms. PMID:25689102

  9. In vitro antimalarial activity of limonoids from Khaya grandifoliola C.D.C. (Meliaceae).

    PubMed

    Bickii, J; Njifutie, N; Foyere, J A; Basco, L K; Ringwald, P

    2000-01-01

    The crude extract from the bark and seeds of Khaya grandifoliola was active in vitro against Plasmodium falciparum with an IC50 value of 13.23 microg/ml. The extract was purified to obtain seven limonoids--methylangolensate (1), 6-methylhydroxyangolensate (2), gedunin (3), 7-deacetylkhivorin (5), 1-deacetylkhivorin (6), swietenolide (7), 6-acetylswietenolide (8)--and one flavonoid, catechin (4). Five limonoids (1, 3, 5, 6, 8) were active with IC50 values between 1.25 and 9.63 microg/ml. Catechin was practically devoid of activity. The most active limonoid, gedunin, exhibited an additive effect when combined with chloroquine. PMID:10661881

  10. In vitro inhibition activity of essential oils from some Lamiaceae species against phytopathogenic fungi.

    PubMed

    Kumar, Vinod; Mathela, C S; Tewari, A K; Bisht, K S

    2014-09-01

    Natural products have been in focus as alternative, effective and safe materials against the phytopathogens. Investigations show Nepeta oils as effective in controlling the food crops decay. The inhibitory effects of essential oils derived from Nepeta leucophylla, Nepeta ciliaris, Nepeta clarkei and Calamintha umbrosa against five phytopthogenic fungi have been determined. In vitro antifungal activity varied with their constituents and target species. More active being the oils containing oxygenated terpenoids. Helminthosporium maydis was sensitive to the all oils, IC50 values have 43.6-109.3 μg mL(-1). The N. leucophylla oil possessing oxygenated iridoids was more effective against H. maydis (IC50 value of 43.6 μg mL(-1)) while N. ciliaris was more active against Fusarium oxysporum (IC50 value of 219.2 μg mL(-1)). The oils were effective against the spore germination of all the tested plant pathogens. PMID:25175652

  11. 2-Arylquinazolin-4(3H)-ones: Inhibitory Activities Against Xanthine Oxidase.

    PubMed

    Zafar, Humaira; Saad, Syed M; Perveen, Shahnaz; Arshia; Malik, Rizwana; Khan, Ajmal; Khan, Khalid M; Choudhary, Muhammad I

    2016-01-01

    2-Arylquinazolin-4(3H)-ones (1-25) were synthesized, and evaluated for their xanthine oxidase inhibitory activity. Significant to moderate activities were exhibited by the compounds 1-3, 7, 9, 13-15, 19-21, and 23 with IC50 between 2.80 - 28.13 µM as compared to the standard allopurinol (IC50 (IC50 = 2.01 ± 0.01 µM). Compounds 4-6, 8, 11-12, 16-18, 22, and 24 demonstrated a weak activity with IC50 values 44.60 - 112.60 µM. Nonetheless, compounds 10 and 25 did not show any activity. Amongst all derivatives, compound 2, containing a C-4´ dimethylamino group, was the most potent inhibitor of the enzyme with an IC50 value comparable to the standard. Kinetics studies on the most active compounds (2, 7, 9, 14, 15, 19, and 20) were conducted in order to determine their modes of inhibition and dissociation constants Ki. Some of the compounds of 2-arylquinazolin-4(3H)-one series were thus identified as potential leads for further studies towards the treatment of hyperuricemia and gout. PMID:26256588

  12. Antiulcer Effect of Extract/Fractions of Eruca sativa : Attenuation of Urease Activity.

    PubMed

    Khan, Haroon; Khan, Murad Ali

    2014-03-19

    Eruca sativa (Rocket salad) is known for its antiulcer properties in the traditional system of treatment. The present study was, therefore, designed to scrutinize its effect on urease activity in vitro. The results demonstrated marked attenuation of urease by the crude extract of various test concentrations with IC50 value of 7.77 mg/mL. On fractionation, marked change in inhibitory profile was observed. The ethyl acetate fraction was the most potent urease inhibitor with IC50 value of 4.17 mg/mL followed by the aqueous fraction with an IC50 value of 5.83 mg/mL. However, hexane did not show significant urease inhibition. In conclusion, the present study illustrated strong antagonism of urease activity and thus validated scientifically the traditional use of the plant in the treatment of ulcers. PMID:24647097

  13. Medicinal plants of Chile: evaluation of their anti-Trypanosoma cruzi activity.

    PubMed

    Muñoz, Orlando M; Maya, Juan D; Ferreira, Jorge; Christen, Philippe; San Martin, José; López-Muñoz, Rodrigo; Morello, Antonio; Kemmerling, Ulrike

    2013-01-01

    The extracts of several plants of Central Chile exhibited anti-Trypanosoma cruzi trypomastigotes activity. Most active extracts were those obtained from Podanthus ovatifolius, Berberis microphylla, Kageneckia oblonga, and Drimys winteri. The active extract of Drimys winteri (IC50 51.2 microg/mL) was purified and three drimane sesquiterpenes were obtained: polygodial, drimenol, and isodrimenin. Isodrimenin and drimenol were found to be active against the trypomastigote form of T. cruzi with IC50 values of 27.9 and 25.1 microM, respectively. PMID:23923616

  14. Anti-cholinesterase activity of lycopodium alkaloids from Vietnamese Huperzia squarrosa (Forst.) Trevis.

    PubMed

    Chuong, Nguyen Ngoc; Huong, Nguyen Thi Thu; Hung, Tran Manh; Luan, Tran Cong

    2014-01-01

    A series of Lycopodium alkaloids, namely lycosquarosine A (1), acetylaposerratinine (2), huperzine A (3), huperzine B (4), 8α-hydrophlemariurine B (5), and huperzinine (6), has been isolated from Vietnamese Huperzia squarrosa. Among them, lycosquarosine A (1) is the new metabolite of the natural source. Lycosquarosine A completely inhibited AChE activity in a dose dependent manner with an IC50 value of 54.3 μg/mL, while acetylaposerratinine (2) showed stronger inhibitory activity than 1 with an IC50 value of 15.2 µg/mL. This result indicates that these alkaloids may be a potent source of AChE inhibitors. PMID:25415478

  15. Evaluation of biological activities of Alpinia mutica Roxb. and its chemical constituents.

    PubMed

    Mustahil, Noorul Adawiyah; Sukari, Mohd Aspollah; Abdul, Ahmad Bustamam; Ali, Nor Azah; Lian, Gwendoline Ee-Cheng

    2013-03-01

    Phytochemicals investigation on rhizomes of Alpinia mutica has afforded five compounds namely 5,6-dehydrokawain (1), flavokawin B (2), pinostrobin (3) and pinocembrin (4) together with β-sitosterol (5). All crude extracts of the plant demonstrated strong cytotoxicity against CEMss (human T4 lymphoblastoid) cancer cells with IC50 values less than 19 μg/mL, while flavokawin B (2) was the most cytotoxic isolate with IC50 value 1.86±0.37 μg/mL. Most of the crude extracts and isolated compounds showed weak activity in antimicrobial and diphenylpicrylhydrazyl (DPPH) radical scavenging activity tests. PMID:23455212

  16. Antimalarial Activity of Anthothecol Derived from Khaya anthotheca (Meliaceae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimalarial activity of anthothecol, a limonoid of Khaya anthotheca (Meliaceae) against Plasmodium falciparum was tested using a [3H]-hypoxanthine and 48 h culture assay in vitro. Anthothecol showed potent antimalarial activity against malarial parasites with IC50 values of 1.4 and 0.17 uM using t...

  17. Antioxidant Activity of Passiflora edulis Sims Leaves

    PubMed Central

    Sunitha, M.; Devaki, K.

    2009-01-01

    Ethanol extract of Passiflora edulis Sims was analyzed for its antioxidant (1,1-diphenyl-2-picryl hydrazyl radical reducing power methods) and phytochemical analysis. The extract was found effective against the antioxidant test models exhibiting an IC50 value of 875±87.83 μg/ml and showed strong potential antioxidant activity in both assays. PMID:20490300

  18. Phenolic constituents from the heartwood of Artocapus altilis and their tyrosinase inhibitory activity.

    PubMed

    Nguyen, Mai Ha Khoa; Nguyen, Hai Xuan; Nguyen, Mai Thanh Thi; Nguyen, Nhan Trung

    2012-02-01

    From the MeOH extract of the heartwood of Artocapus altilis, thirteen phenolic compounds have been isolated, namely curcumin (1), desmethoxycurcumin (2), retrodihydrochalcone (3), apigenin (4), tangeretin (5), nobiletin (6), O-methyldehydrodieugenol (7), dehydrodieugenol (8), beta-hydroxypropiovanillone (9), p-coumaric acid (10), p-hydroxybenzaldehyde (11), vanillin (12), and vanillic acid (13). This is the first report on the presence of these compounds in the heartwood of A. altilis. Compounds 1, 2, and 10 showed more potent tyrosinase inhibitory activities, with IC50 values ranging from 2.3 to 42.0 microM, than the positive control kojic acid (IC50, 44.6 microM). The most active compound, p-coumaric acid (10) (IC50, 2.3 microM), was 22 times more active in tyrosinase inhibitory activity than kojic acid. PMID:22474950

  19. Drimanes from Drimys brasiliensis with leishmanicidal and antimalarial activity

    PubMed Central

    Claudino, Vanessa Duarte; da Silva, Kesia Caroline; Cechinel, Valdir; Yunes, Rosendo Augusto; Monache, Franco Delle; Giménez, Alberto; Salamanca, Efrain; Gutierrez-Yapu, David; Malheiros, Angela

    2013-01-01

    This paper evaluates CHCl3 and CH3OH extracts of the stem bark, branches and leaves of Drimys brasiliensis and drimane sesquiterpenes isolated from the stem bark against strains of Leishmania amazonensis and Leishmania braziliensis promastigotes and Plasmodium falciparum trophozoites. All of the extracts and compounds were tested in cell lines in comparison with reference standards and cell viability was determined by the XTT method. The CHCl3 and CH3OH extracts from the stem bark and branches yielded promising results against two strains of Leishmania, with 50% inhibitory concentrations (IC50 ) values ranging from 39-100 µg/mL. The CHCl3 extract of the stem bark returned IC50 values of 39 and 40.6 µg/mL for L. amazonensis and L. braziliensis, respectively. The drimanes were relatively effective: 1-β-(p-coumaroyloxy)-polygodial produced IC50 values of 5.55 and 2.52 µM for L. amazonensis and L. braziliensis, respectively, compared with 1-β-(p-methoxycinnamoyl)-polygodial, which produced respective IC50 values of 15.85 and 17.80 µM. The CHCl3 extract demonstrated activity (IC50 of 3.0 µg/mL) against P. falciparum. The IC50 values of 1-β-(p-cumaroyloxyl)-polygodial and 1-β-(p-methoxycinnamoyl)-polygodial were 1.01 and 4.87 µM, respectively, for the trophozoite strain. Therefore, the results suggest that D. brasiliensis is a promising plant from which to obtain new and effective antiparasitic agents. PMID:23579790

  20. Antiplasmodial activities of gold(I) complexes involving functionalized N-heterocyclic carbenes.

    PubMed

    Hemmert, Catherine; Ramadani, Arba Pramundita; Boselli, Luca; Fernández Álvarez, Álvaro; Paloque, Lucie; Augereau, Jean-Michel; Gornitzka, Heinz; Benoit-Vical, Françoise

    2016-07-01

    A series of twenty five molecules, including imidazolium salts functionalized by N-, O- or S-containing groups and their corresponding cationic, neutral or anionic gold(I) complexes were evaluated on Plasmodium falciparum in vitro and then on Vero cells to determine their selectivity. Among them, eight new compounds were synthesized and fully characterized by spectroscopic methods. The X-ray structures of three gold(I) complexes are presented. Except one complex (18), all the cationic gold(I) complexes show potent antiplasmodial activity with IC50 in the micro- and submicromolar range, correlated with their lipophilicity. Structure-activity relationships enable to evidence a lead-complex (21) displaying a good activity (IC50=210nM) close to the value obtained with chloroquine (IC50=514nM) and a weak cytotoxicity. PMID:27240469

  1. Evaluation of Antileishmanial Activity of Albaha Medicinal Plants against Leishmania amazonensis

    PubMed Central

    Al-Sokari, Saeed S.; Ali, Nasser A. Awadh; Monzote, Lianet; Al-Fatimi, Mohamed A.

    2015-01-01

    Sixteen methanolic extracts obtained from thirteen plant species, selected either from ethnobotanical or chemotaxonomical data, were screened for their antileishmanial activity against Leishmania amazonensis. The cytotoxic activity against normal peritoneal macrophages from normal BALB/c mice was also determined. Eight extracts had IC50 values ranging from <12.5 to 37.8 µg/mL against promastigotes. Achillea biebersteinii flower, Euphorbia helioscopia, and Solanum incanum leaf extracts showed antileishmanial activities with IC50 between <12.5–26.9 µg/mL and acceptable selectivity indices of 8–5. The other leishmanicidal plant extracts, with IC50 ranging from 18.0 to 29.5 µg/mL, exhibited low selectivity indices. PMID:26357662

  2. Antimicrobial and antiprotozoal activities of secondary metabolites from the fungus Eurotium repens

    PubMed Central

    Gao, Jiangtao; Radwan, Mohamed M.; León, Francisco; Wang, Xiaoning; Jacob, Melissa R.; Tekwani, Babu L.; Khan, Shabana I.; Lupien, Shari; Hill, Robert A.; Dugan, Frank M.; Cutler, Horace G.

    2011-01-01

    In this study, we examined in vitro antibacterial, antifungal, antimalarial, and antileishmanial activities of secondary metabolites (1–8) isolated from the fungus Eurotium repens. All compounds showed mild to moderate antibacterial or antifungal or both activities except 7. The activity of compound 6 was the best of the group tested. The in vitro antimalarial evaluation of these compounds revealed that compounds 1–3, 5, and 6 showed antimalarial activities against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum with IC50 values in the range of 1.1–3.0 μg/ml without showing any cytotoxicity to the mammalian cells. Compound 5 displayed the highest antimalarial activity. Antileishmanial activity against Leishmania donovani promastigotes was observed for compounds 1–6 with IC50 values ranging from 6.2 to 23 μg/ml. Antileishmanial activity of compounds 5 and 6 (IC50 values of 7.5 and 6.2 μg/ml, respectively) was more potent than 1–4 (IC50 values ranging from 19–23 μg/ml). Compounds 7 and 8 did not show any antiprotozoal effect. Preliminary structure and activity relationship studies indicated that antibacterial, antifungal, antimalarial, and antileishmanial activities associated with phenol derivates (1–6) seem to be dependent on the number of double bonds in the side chain, which would be important for lead optimization in the future. PMID:23024574

  3. Antioxidant activities of Physalis peruviana.

    PubMed

    Wu, Sue-Jing; Ng, Lean-Teik; Huang, Yuan-Man; Lin, Doung-Liang; Wang, Shyh-Shyan; Huang, Shan-Ney; Lin, Chun-Ching

    2005-06-01

    Physalis peruviana (PP) is a widely used medicinal herb for treating cancer, malaria, asthma, hepatitis, dermatitis and rheumatism. In this study, the hot water extract (HWEPP) and extracts prepared from different concentrations of ethanol (20, 40, 60, 80 and 95% EtOH) from the whole plant were evaluated for antioxidant activities. Results displayed that at 100 mug/ml, the extract prepared from 95% EtOH exhibited the most potent inhibition rate (82.3%) on FeCl2-ascorbic acid induced lipid peroxidation in rat liver homogenate. At concentrations 10-100 microg/ml, this extract also demonstrated the strongest superoxide anion scavenging and inhibitory effect on xanthine oxidase activities. In general, the ethanol extracts revealed a stronger antioxidant activity than alpha-tocopherol and HWEPP. Compared to alpha-tocopherol, the IC50 value of 95% EtOH PP extract was lower in thiobarbituric acid test (IC50=23.74 microg/ml vs. 26.71 microg/ml), in cytochrome c test (IC50=10.40 microg/ml vs. 13.39 microg/ml) and in xanthine oxidase inhibition test (IC50=8.97 microg/ml vs. 20.68 microg/ml). The present study concludes that ethanol extracts of PP possess good antioxidant activities, and the highest antioxidant properties were obtained from the 95% EtOH PP. PMID:15930727

  4. Xanthine oxidase inhibitory activity of Vietnamese medicinal plants.

    PubMed

    Nguyen, Mai Thanh Thi; Awale, Suresh; Tezuka, Yasuhiro; Tran, Quan Le; Watanabe, Hiroshi; Kadota, Shigetoshi

    2004-09-01

    Among 288 extracts, prepared from 96 medicinal plants used in Vietnamese traditional medicine to treat gout and related symptoms, 188 demonstrated xanthine oxidase (XO) inhibitory activity at 100 microg/ml, with 46 having greater than 50% inhibition. At 50 microg/ml, 168 of the extracts were active, with 21 possessing more than 50% inhibition. At 25 microg/ml, 146 extracts exhibited inhibitory activity, with 8 showing over 50% inhibition, while 126 extracts presented activity at 10 microg/ml, with 2 having greater than 50% inhibition. The MeOH extracts of Artemisia vulgaris, Caesalpinia sappan (collected at the Seven-Mountain area), Blumea balsamifera (collected in Lam Dong province), Chrysanthemum sinense and MeOH-H(2)O extract of Tetracera scandens (Khanh Hoa province) exhibited strong XO inhibitory activity with IC(50) values less than 20 microg/ml. The most active extract was the MeOH extract of the flower of C. sinense with an IC(50) value of 5.1 microg/ml. Activity-guided fractionation of the MeOH extract led to the isolation of caffeic acid (1), luteolin (2), eriodictyol (3), and 1,5-di-O-caffeoylquinic acid (4). All these compounds showed significant XO inhibitory activity in a concentration-dependent manner, and the activity of 2 was more potent (IC(50) 1.3 microM) than the clinically used drug, allopurinol (IC(50) 2.5 microM). PMID:15340229

  5. Stictic acid derivatives from the lichen Usnea articulata and their antioxidant activities.

    PubMed

    Lohézic-Le Dévéhat, Françoise; Tomasi, Sophie; Elix, John A; Bernard, Aurélie; Rouaud, Isabelle; Uriac, Philippe; Boustie, Joël

    2007-07-01

    Two new beta-orcinol depsidones, 1 and 2, together with 13 known compounds were isolated from the lichen Usnea articulata. The structures of 1 and 2 were elucidated by spectroscopic analyses and those of known compounds by comparison of their spectroscopic data with literature values or by direct comparison with authentic standards. Compounds 1, 2, and 5 exhibited moderate antiradical activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The depsidones 4 and 5 showed better superoxide anion scavenging activity (IC50 = 566 and 580 microM, respectively) than quercetin (IC50 = 754 microM). PMID:17629329

  6. Active components with inhibitory activities on IFN-γ/STAT1 and IL-6/STAT3 signaling pathways from Caulis Trachelospermi.

    PubMed

    Liu, Xiao-Ting; Wang, Zhe-Xing; Yang, Yu; Wang, Lin; Sun, Ruo-Feng; Zhao, Yi-Min; Yu, Neng-Jiang

    2014-01-01

    Initial investigation for new active herbal extract with inhibiting activity on JAK/STAT signaling pathway revealed that the extract of Caulis Trachelospermi, which was separated by 80% alcohol extraction and subsequent HP-20 macroporous resin column chromatography, was founded to strongly inhibit IFN-γ-induced STAT1-responsive luciferase activity (IFN-γ/STAT1) with IC50 value of 2.43 μg/mL as well as inhibiting IL-6-induced STAT3-responsive luciferase activity (IL-6/STAT3) with IC50 value of 1.38 μg/mL. Subsequent study on its active components led to the isolation and identification of two new dibenzylbutyrolactone lignans named 4-demethyltraxillaside (1) and nortrachelogenin 4-O-β-D-glucopyranoside (2), together with six known compounds. The lignan compounds 1-4 together with other lignan compounds isolated in previous study were tested the activities on IFN-γ/STAT1 and IL-6/STAT3 pathways. The following result showed that the main components trachelogenin and arctigenin had corresponding activities on IFN-γ/STAT1 pathway with IC50 values of 3.14 μM and 9.46 μM as well as trachelogenin, arctigenin and matairesinol strongly inhibiting IL-6/STAT3 pathway with IC50 values of 3.63 μM, 6.47 μM and 2.92 μM, respectively. PMID:25100250

  7. Synthesis and antibacterial activity of alaremycin derivatives for the porphobilinogen synthase.

    PubMed

    Iwai, Noritaka; Nakayama, Kyosuke; Oku, Jumpei; Kitazume, Tomoya

    2011-05-15

    The preparation and the antibacterial activity of alaremycin derivatives such as their CF(3)-derivatives and (R)- and (S)-4-oxo-5-acetylaminohexanoic acid for the porphobilinogen synthase (PBGS), were described. The IC(50) values of the antibacterial activity of the prepared materials for the inhibitor of PBGS, were determined using PBGS assay. PMID:21514151

  8. Inhibitory Activity of Marine Sponge-Derived Natural Products against Parasitic Protozoa

    PubMed Central

    Orhan, Ilkay; Şener, Bilge; Kaiser, Marcel; Brun, Reto; Tasdemir, Deniz

    2010-01-01

    In this study, thirteen sponge-derived terpenoids, including five linear furanoterpenes: furospinulosin-1 (1), furospinulosin-2 (2), furospongin-1 (3), furospongin-4 (4), and demethylfurospongin-4 (5); four linear meroterpenes: 2-(hexaprenylmethyl)-2-methylchromenol (6), 4-hydroxy-3-octaprenylbenzoic acid (7), 4-hydroxy-3-tetraprenyl-phenylacetic acid (8), and heptaprenyl-p-quinol (9); a linear triterpene, squalene (10); two spongian-type diterpenes dorisenone D (11) and 11β-acetoxyspongi-12-en-16-one (12); a scalarane-type sesterterpene; 12-epi-deoxoscalarin (13), as well as an indole alkaloid, tryptophol (14) were screened for their in vitro activity against four parasitic protozoa; Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum. Cytotoxic potential of the compounds on mammalian cells was also assessed. All compounds were active against T. brucei rhodesiense, with compound 8 being the most potent (IC50 0.60 μg/mL), whereas 9 and 12 were the most active compounds against T. cruzi, with IC50 values around 4 μg/mL. Compound 12 showed the strongest leishmanicidal activity (IC50 0.75 μg/mL), which was comparable to that of miltefosine (IC50 0.20 μg/mL). The best antiplasmodial effect was exerted by compound 11 (IC50 0.43 μg/mL), followed by compounds 7, 10, and 12 with IC50 values around 1 μg/mL. Compounds 9, 11 and 12 exhibited, besides their antiprotozoal activity, also some cytotoxicity, whereas all other compounds had low or no cytotoxicity towards the mammalian cell line. This is the first report of antiprotozoal activity of marine metabolites 1–14, and points out the potential of marine sponges in discovery of new antiprotozoal lead compounds. PMID:20161970

  9. Design, synthesis, acetylcholinesterase inhibition and larvicidal activity of girgensohnine analogs on Aedes aegypti, vector of dengue fever.

    PubMed

    Carreño Otero, Aurora L; Vargas Méndez, Leonor Y; Duque L, Jonny E; Kouznetsov, Vladimir V

    2014-05-01

    Girgensohnine alkaloid was used as a natural model in the design and generation of new alkaloid-like α-aminonitrile series that was completed by the use of SSA-catalyzed Strecker reaction between commercial and inexpensive substituted benzaldehydes, piperidine (pyrrolidine, morpholine and N-methylpiperazine) and acetone cyanohydrin. Calculated ADMETox parameters of the designed analogs revealed their good pharmacokinetic profiles indicating lipophilic characteristics. In vitro AChE enzyme test showed that obtained α-aminonitriles could be considered as AChEIs with micromolar IC50 values ranging from 42.0 to 478.0 μM (10.3-124.0 μg/mL). Among this series, the best AChE inhibitor was the pyrrolidine α-aminonitrile 3 (IC50 = 42 μM), followed by the piperidine α-aminonitriles 2 and 6 (IC50 = 45 μM and IC50 = 51 μM, respectively), and the compound 7 (IC50 = 51 μM). In vivo insecticidal activity of more active AChEIs against Aedes aegypti larvae was also performed showing a good larvicidal activity at concentrations less than 140 ppm, highlighting products 2 and 7 that could serve as lead compounds to develop new potent and selective insecticides. PMID:24704612

  10. Synthesis and antiviral activity of a series of novel N-phenylbenzamide and N-phenylacetophenone compounds as anti-HCV and anti-EV71 agents

    PubMed Central

    Jiang, Zhi; Wang, Huiqiang; Li, Yanping; Peng, Zonggen; Li, Yuhuan; Li, Zhuorong

    2015-01-01

    A series of novel N-phenylbenzamide and N-phenylacetophenone compounds were synthesized and evaluated for their antiviral activity against HCV and EV71 (strain SZ-98). The biological results showed that three compounds (23, 25 and 41) exhibited considerable anti-HCV activity (IC50=0.57–7.12 μmol/L) and several compounds (23, 28, 29, 30, 31 and 42) displayed potent activity against EV71 with the IC50 values lower than 5.00 μmol/L. The potency of compound 23 (IC50=0.57 μmol/L) was superior to that of reported compounds IMB-1f (IC50=1.90 μmol/L) and IMB-1g (IC50=1.00 μmol/L) as anti-HCV agents, and compound 29 possessed the highest anti-EV71 activity, comparable to the comparator drug pirodavir. The efficacy in vivo and antiviral mechanism of these compounds warrant further investigations. PMID:26579447

  11. Physiological Activities of Thiacremonone Produced in High Temperature and High Pressure Treated Garlic

    PubMed Central

    Woo, Koan Sik; Hwang, In Guk; Kim, Hyun Young; Lee, Sang Hoon; Jeong, Heon Sang

    2016-01-01

    To examine the possibility of using thiacremonone isolated from high-temperature-high-pressure treated garlic, this study investigated the physiological activities properties. The IC50 values of hydroxyl, superoxide, hydrogen peroxide, and nitric oxide radical scavenging activities of thiacremonone were 92.50, 65.05, 12.60, and 81.53 μg/mL, respectively. On the other hand, the activities of vitamin C were 104.93, 99.43, 42.42, and 122.64 μg/mL, and the activities of butylated hydroxyanisole were 37.22, 68.45, 22.47, and 40.54 μg/mL, respectively. The IC50 value of ACE inhibition activities of thiacremonone and captoprill were 0.265 and 0.036 μg/mL, respectively. The IC50 value of xanthine oxidase inhibition activities of thiacremonone and allopurinol were 39.430 and 9.346 μg/mL, respectively. The IC50 value of tyrosinase inhibition activities of thiacremonone and kojic acid were 101.931 and 65.648 μg/mL, respectively. PMID:27069909

  12. Physiological Activities of Thiacremonone Produced in High Temperature and High Pressure Treated Garlic.

    PubMed

    Woo, Koan Sik; Hwang, In Guk; Kim, Hyun Young; Lee, Sang Hoon; Jeong, Heon Sang

    2016-03-01

    To examine the possibility of using thiacremonone isolated from high-temperature-high-pressure treated garlic, this study investigated the physiological activities properties. The IC50 values of hydroxyl, superoxide, hydrogen peroxide, and nitric oxide radical scavenging activities of thiacremonone were 92.50, 65.05, 12.60, and 81.53 μg/mL, respectively. On the other hand, the activities of vitamin C were 104.93, 99.43, 42.42, and 122.64 μg/mL, and the activities of butylated hydroxyanisole were 37.22, 68.45, 22.47, and 40.54 μg/mL, respectively. The IC50 value of ACE inhibition activities of thiacremonone and captoprill were 0.265 and 0.036 μg/mL, respectively. The IC50 value of xanthine oxidase inhibition activities of thiacremonone and allopurinol were 39.430 and 9.346 μg/mL, respectively. The IC50 value of tyrosinase inhibition activities of thiacremonone and kojic acid were 101.931 and 65.648 μg/mL, respectively. PMID:27069909

  13. An antagonistic activity of etizolam on platelet-activating factor (PAF). In vitro effects on platelet aggregation and PAF receptor binding.

    PubMed

    Mikashima, H; Takehara, S; Muramoto, Y; Khomaru, T; Terasawa, M; Tahara, T; Maruyama, Y

    1987-08-01

    The antagonistic effect of etizolam, an anti-anxiety drug, on platelet-activating factor (PAF) was investigated in rabbit platelets in vitro. Etizolam inhibited PAF-induced aggregation in a dose-dependent manner, with an IC50 of 3.8 microM, about one tenth that of triazolam (IC50 = 30 microM). At 300 microM, it inhibited both ADP and arachidonic acid-induced aggregation only slightly, while the other anti-anxiety drugs tested had no effect on PAF-induced aggregation even at this concentration. Etizolam and triazolam inhibited the specific binding of 3H-PAF to PAF receptor sites on washed rabbit platelets with IC50 values of 22 nM and 320 nM, respectively. Diazepam and estazolam were inactive even at 1 microM. These results indicate that etizolam is a specific antagonist of PAF. PMID:2890779

  14. Studies on the phenylethanoid glycosides with anti-complement activity from Paulownia tomentosa var. tomentosa wood.

    PubMed

    Si, Chuan-Ling; Deng, Xiao-Juan; Liu, Zhong; Kim, Jin-Kyu; Bae, Young-Soo

    2008-01-01

    Four epimeric phenylethanoid glycosides, including a new one, R,S-beta-ethoxy-beta-(3,4-dihydroxyphenyl)-ethyl-O-alpha-L-rhamnopyranosyl(1-->3)-beta-D-(6-O-E-caffeoyl)-glucopyranoside named isoilicifolioside A (1), and three known compounds, ilicifolioside A (2), campneoside II (3), and isocampneoside II (4), were isolated from Paulownia tomentosa var. tomentosa wood. The structures of the four compounds were elucidated by the interpretation of 1D and 2D NMR and MS spectra. This is the first report of the chemical profile of this tree. Compounds 1-4 exhibited excellent anti-complement activity with IC(50) values less than 74 microM, compared with tiliroside (IC(50) = 104 microM) and rosmarinic acid (IC(50) = 182 microM) that were used as positive controls. PMID:19031237

  15. Acylphloroglucinol derivatives from Decaspermum gracilentum and their antiradical and cytotoxic activities.

    PubMed

    Sun, Meng; Gobu, Fekadu-Roge; Pan, Dong; Li, Ya; Gao, Kun

    2016-01-01

    Two new acylphloroglucinol derivatives, 1-(hexanoyl)phloroglucinol-α-d-arabinopyranoside (1) and 1-(hexanoyl)phloroglucinol-β-d-glucopyranoside (2), along with two known ones, 1-(acetyl)phloroglucinol-β-d-glucopyranoside (3) and ethyl 2,4,6-trihydroxybenzoate (4), were isolated from the EtOAc soluble fraction of EtOH extract of Decaspermum gracilentum. The structures of the new compounds were determined by extensive spectroscopic analyses including HRESIMS, 1D and 2D NMR data. Interestingly, all of the compounds showed ABTS(·+) radical scavenging activity with the IC50 values less than 10 μM. Furthermore, compounds 3 and 4 displayed moderate cytotoxicity on human non-small-cell lung carcinoma cell line A549 (IC50 = 50.9 μΜ) and human renal carcinoma cell line 786-O (IC50 = 38.6 μΜ), respectively. PMID:26690508

  16. Cytotoxic Activity and Chemical Composition of the Root Extract from the Mexican Species Linum scabrellum: Mechanism of Action of the Active Compound 6-Methoxypodophyllotoxin

    PubMed Central

    Alejandre-García, Ivonne; Álvarez, Laura; Cardoso-Taketa, Alexandre; González-Maya, Leticia; Antúnez, Mayra; Salas-Vidal, Enrique; Díaz, J. Fernando; Marquina-Bahena, Silvia; Villarreal, María Luisa

    2015-01-01

    The cytotoxic activity and the chemical composition of the dichloromethane/methanol root extract of Linum scabrellum Planchon (Linaceae) were analyzed. Using NMR spectra and mass spectrometry analyses of the extract we identified eight main constituents: oleic acid (1), octadecenoic acid (2), stigmasterol (3), α-amyrin (4), pinoresinol (5), 6 methoxypodophyllotoxin (6), coniferin (7), and 6-methoxypodophyllotoxin-7-O-β-D-glucopyranoside (8). By using the sulforhodamine B assay, an important cytotoxic activity against four human cancer cell lines, HF6 colon (IC50 = 0.57 μg/mL), MCF7 breast (IC50 = 0.56 μg/mL), PC3 prostate (IC50 = 1.60 μg/mL), and SiHa cervical (IC50 = 1.54 μg/mL), as well as toward the normal fibroblasts line HFS-30 IC50 = 1.02 μg/mL was demonstrated. Compound 6 (6-methoxypodophyllotoxin) was responsible for the cytotoxic activity exhibiting an IC50 value range of 0.0632 to 2.7433 µg/mL against the tested cell lines. Cell cycle studies with compound 6 exhibited a cell arrest in G2/M of the prostate PC3 cancer cell line. Microtubule disruption studies demonstrated that compound 6 inhibited the polymerization of tubulin through its binding to the colchicine site (binding constant Kb = 7.6 × 106 M−1). A dose-response apoptotic effect was also observed. This work constitutes the first investigation reporting the chemical composition of L. scabrellum and the first study determining the mechanism of action of compound 6. PMID:26246833

  17. Novel anti-Cryptosporidium activity of known drugs identified by high-throughput screening against parasite fatty acyl-CoA binding protein (ACBP)

    PubMed Central

    Fritzler, Jason M.; Zhu, Guan

    2012-01-01

    Background Cryptosporidium parvum causes an opportunistic infection in AIDS patients, and no effective treatments are yet available. This parasite possesses a single fatty acyl-CoA binding protein (CpACBP1) that is localized to the unique parasitophorous vacuole membrane (PVM). The major goal of this study was to identify inhibitors from known drugs against CpACBP1 as potential new anti-Cryptosporidium agents. Methods A fluorescence assay was developed to detect CpACBP1 activity and to identify inhibitors by screening known drugs. Efficacies of top CpACBP1 inhibitors against Cryptosporidium growth in vitro were evaluated using a quantitative RT–PCR assay. Results Nitrobenzoxadiazole-labelled palmitoyl-CoA significantly increased the fluorescent emission upon binding to CpACBP1 (excitation/emission 460/538 nm), which was quantified to determine the CpACBP1 activity and binding kinetics. The fluorescence assay was used to screen a collection of 1040 compounds containing mostly known drugs, and identified the 28 most active compounds that could inhibit CpACBP1 activity with sub-micromolar IC50 values. Among them, four compounds displayed efficacies against parasite growth in vitro with low micromolar IC50 values. The effective compounds were broxyquinoline (IC50 64.9 μM), cloxyquin (IC50 25.1 μM), cloxacillin sodium (IC50 36.2 μM) and sodium dehydrocholate (IC50 53.2 μM). Conclusions The fluorescence ACBP assay can be effectively used to screen known drugs or other compound libraries. Novel anti-Cryptosporidium activity was observed in four top CpACBP1 inhibitors, which may be further investigated for their potential to be repurposed to treat cryptosporidiosis and to serve as leads for drug development. PMID:22167242

  18. In vitro antimalarial activity and cytotoxicity of cochlospermum tinctorium and C. planchonii leaf extracts and essential oils.

    PubMed

    Benoit-Vical, F; Valentin, A; Mallié, M; Bastide, J M; Bessière, J M

    1999-05-01

    The antimalarial and toxicological properties of Cochlospermum tinctorium and C. planchonii extracts and essential oils prepared from their leaves were studied. The oil components were extracted by hydrodistillation of the plant leaves and characterized by gas chromatography and mass spectrometry. Crude extracts and oils were tested for in vitro antimalarial activity on Plasmodium falciparum. The IC50 were evaluated after 24 and 72 h contact between the oils and the parasite culture, and ranged from 22 to 500 micrograms/ml. C. planchonii leaf oil yielded the best antimalarial effect (IC50: 22-35 micrograms/ml), while the most potent effect from crude leaf extracts was induced by C. tinctorium. The cytotoxicity of the leaf crude extracts and oils was assessed on the K562 cell line and showed IC50 values ranging between 33 and 2000 micrograms/ml. PMID:10364849

  19. Potent Radical-Scavenging Activities of Thiamin and Thiamin Diphosphate

    PubMed Central

    Okai, Yasuji; Higashi-Okai, Kiyoka; F. Sato, Eisuke; Konaka, Ryusei; Inoue, Masayasu

    2007-01-01

    Various radical-scavenging activities of thiamin and thiamin diphosphate (TDP) were found in some in vitro experiments. Thiamin and TDP caused considerable suppressive effects on superoxide generation in hypoxanthine and xanthine oxidase system which was measured by a sensitive chemiluminescence method using 2-methyl-6-[p-methylphenyl]-3,7-dihydroimidazo[1,2-alpha]pyrazin-3-one (MCLA), and their 50% inhibition (IC50) values were estimated to be 158 and 56 µM, respectively. They also showed the significant suppression against hydroperoxide generation derived from oxidized linoleic acid which was estimated by aluminum chloride method and their IC50 values were calculated to be 260 and 46 µM. They further prevented the oxygen radical generation in opsonized zymosan-stimulated human blood neutrophils which was shown by chemiluminescence method using luminol, and their IC50 values were calculated to be 169 and 38 µM. In contrast, they caused weak but significantly suppressive effects on the hydroxyl radical generation by Fenton reaction which was measured by electric spin resonance (ESR) method, their IC50 values were calculated to be 8.45 and 1.46 mM respectively. These results strongly suggest a possibility that thiamin and TDP play as radical scavengers in cell-free and cellular systems. PMID:18437212

  20. Inhibitory Effects of Standardized Extracts of Phyllanthus amarus and Phyllanthus urinaria and Their Marker Compounds on Phagocytic Activity of Human Neutrophils

    PubMed Central

    Yuandani; Ilangkovan, Menaga; Mohamad, Hazni Falina; Husain, Khairana; Abdul Razak, Amirul Faiz

    2013-01-01

    The standardized methanol extracts of Phyllanthus amarus and P. urinaria, collected from Malaysia and Indonesia, and their isolated chemical markers, phyllanthin and hypophyllanthin, were evaluated for their effects on the chemotaxis, phagocytosis and chemiluminescence of human phagocytes. All the plant extracts strongly inhibited the migration of polymorphonuclear leukocytes (PMNs) with the Malaysian P. amarus showing the strongest inhibitory activity (IC50 value, 1.1 µg/mL). There was moderate inhibition by the extracts of the bacteria engulfment by the phagocytes with the Malaysian P. amarus exhibiting the highest inhibition (50.8% of phagocytizing cells). The Malaysian P. amarus and P. urinaria showed strong reactive oxygen species (ROS) inhibitory activity, with both extracts exhibiting IC50 value of 0.7 µg/mL. Phyllanthin and hypophyllanthin exhibited relatively strong activity against PMNs chemotaxis, with IC50 values slightly lower than that of ibuprofen (1.4 µg/mL). Phyllanthin exhibited strong inhibitory activity on the oxidative burst with an IC50 value comparable to that of aspirin (1.9 µg/mL). Phyllanthin exhibited strong engulfment inhibitory activity with percentage of phagocytizing cells of 14.2 and 27.1% for neutrophils and monocytes, respectively. The strong inhibitory activity of the extracts was due to the presence of high amounts of phyllanthin and hypophyllanthin although other constituents may also contribute. PMID:23737840

  1. Inhibitory activity of chlorogenic acids in decaffeinated green coffee beans against porcine pancreas lipase and effect of a decaffeinated green coffee bean extract on an emulsion of olive oil.

    PubMed

    Narita, Yusaku; Iwai, Kazuya; Fukunaga, Taiji; Nakagiri, Osamu

    2012-01-01

    A decaffeinated green coffee bean extract (DGCBE) inhibited porcine pancreas lipase (PPL) activity with an IC50 value of 1.98 mg/mL. Six different chlorogenic acids in DGCBE contributed to this PPL inhibition, accounting for 91.8% of the inhibitory activity. DGCBE increased the droplet size and decreased the specific surface area of an olive oil emulsion. PMID:23221697

  2. In vitro neuraminidase inhibitory concentration (IC50) of four neuraminidase inhibitors against clinical isolates of the influenza viruses circulating in the 2010-2011 to 2014-2015 Japanese influenza seasons.

    PubMed

    Ikematsu, Hideyuki; Kawai, Naoki; Iwaki, Norio; Kashiwagi, Seizaburo

    2016-09-01

    To assess the extent of viral resistance to the four neuraminidase inhibitors (NAIs), we measured their 50% inhibitory concentration (IC50) for influenza virus isolates from the 2014-2015 influenza season for comparison with those circulating in the 2010-2011 to 2013-2014 influenza seasons. Viral isolation was done with specimens obtained prior to treatment, and the type and subtype of influenza was determined by RT-PCR using type- and subtype-specific primers. The IC50 was determined by a neuraminidase inhibition assay using a fluorescent substrate. IC50 was measured for 200 influenza A(H3N2) and 19 influenza B in the 2014-2015 season, and no virus with highly reduced sensitivity to the four NAIs was detected. The ratios of the geometric means of the A(H3N2) IC50s of 2014-2015 to those of the 2010-2011, 2011-2012, 2012-2013, and 2013-2014 seasons ranged from 0.72 to 1.05, 0.82 to 1.22, 0.69 to 1.00, and 0.70 to 1.03, respectively. The ratios of the geometric mean of the B IC50s to the previous four seasons ranged from 0.59 to 1.28, 0.66 to 1.34, 0.84 to 1.21, and 1.06 to 1.47, respectively. There was no trend in the change of the IC50s for A(H3N2) or B. Significant differences were found in some seasons, but the differences in the IC50s were all less than two fold. These results show change in the geometric mean IC50 by season but with no trend, which indicates that the influence of viral mutation on the effectiveness of these NAIs was minute for A(H3N2) and B over the past five seasons. PMID:27346379

  3. Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds from Allanblackia monticola and Symphonia globulifera.

    PubMed

    Lenta, Bruno Ndjakou; Vonthron-Sénécheau, Catherine; Weniger, Bernard; Devkota, Krishna Prasad; Ngoupayo, Joseph; Kaiser, Marcel; Naz, Qamar; Choudhary, Muhammad Iqbal; Tsamo, Etienne; Sewald, Norbert

    2007-01-01

    In a preliminary antiprotozoal screening of several Clusiaceae species, the methanolic extracts of Allanblackia monticola and Symphonia globulifera showed high in vitro leishmanicidal activity. Further bioguided phytochemical investigation led to the isolation of four benzophenones: guttiferone A (1), garcinol (2), cambogin (3) and guttiferone F (4), along with three xanthones: allanxanthone A (5), xanthone V1 (6) and globulixanthone C (7) as active constituents. Compounds 1 and 6 were isolated from S. globulifera leaves, while compounds 2-5 were obtained from A. monticola fruits. Guttiferone A (1) and F (4) showed particulary strong leishmanicidal activity in vitro, with IC50 values (0.2 microM and 0.16 microM, respectively) comparable to that of the reference compound, miltefosine (0.46 microM). Although the leishmanicidal activity is promising, the cytotoxicity profile of these compounds prevent at this state further in vivo biological evaluation. In addition, all the isolated compounds were tested in vitro for their anticholinesterase properties. The four benzophenones showed potent anticholinesterase properties towards acetylcholinesterase (AChE) and butylcholinesterase (AChE). For AChE, the IC50 value (0.66 microM) of garcinol (2) was almost equal to that of the reference compound galanthamine (0.50 microM). Furthermore, guttiferone A (1) and guttiferone F (4) (IC50 = 2.77 and 3.50 microM, respectively) were more active than galanthamine (IC50 = 8.5) against BChE. PMID:17960072

  4. In vitro antiplasmodial activity of some medicinal plants of Burkina Faso.

    PubMed

    Ouattara, Lamoussa Paul; Sanon, Souleymane; Mahiou-Leddet, Valérie; Gansané, Adama; Baghdikian, Béatrice; Traoré, Abdoulaye; Nébié, Issa; Traoré, Alfred S; Azas, Nadine; Ollivier, Evelyne; Sirima, Sodiomon Bienvenu

    2014-01-01

    Malaria remains a major public health problem due to the emergence and spread of Plasmodium falciparum drug resistance. There is an urgent need to investigate new sources of antimalarial drugs which are more effective against Plasmodium falciparum. One of the potential sources of antimalarial drugs is traditional medicinal plants. In this work, we studied the in vitro antiplasmodial activity of chloromethylenic, methanolic, and MeOH/H2O (1/1) crude extracts and decoction obtained from eight medicinal plants collected in Burkina Faso and of total alkaloids for five plants. Extracts were evaluated in vitro for efficacy against Plasmodium falciparum strain K1, which is resistant to chloroquine, pyrimethamine and proguanil using the fluorescence-based SYBR Green I assay. The antiproliferative activity on human-derived hepatoma cell line HepG2 and Chinese hamster ovary (CHO) cells was evaluated using the 3-[4,5-dimethylthyazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test in order to determine the selectivity index. Among the plant extracts tested for in vitro antiplasmodial activity, 16 were considered to be inactive (with IC50 > 10 μg/ml), six showed a moderate activity (5 < IC50 ≤ 10 μg/ml), and six were found to have a good in vitro activity with IC50 value ≤ 5 μg/ml. The highest antiplasmodial activity was found for extracts from: the alkaloid leaf extract and the chloromethylenic extracts of Combretum fragrans (IC50 = 3 μg/ml, IC50 = 5 μg/ml), the total alkaloids and the chloromethylenic leaf extracts of Combretum collinum (IC50 = 4 μg/ml), the MeOH/H2O leaf extract of Terminalia avicennioides (IC50 = 3.5 μg/ml), and the alkaloid leaf extract of Pavetta crassipes (IC50 = 5 μg/ml). Three other extracts showed moderate antiplasmodial activity (5 < IC50 ≤ 10 μg/ml): Terminalia avicennioides and Combretum fragrans methanolic extracts and Acacia kirkii alkaloid leaf extract (IC50 = 6.5, 9 and 10 μg/ml respectively). The Terminalia avicennioides crude

  5. Synthesis, antioxidant and anticholinesterase activities of novel coumarylthiazole derivatives.

    PubMed

    Kurt, Belma Zengin; Gazioglu, Isil; Sonmez, Fatih; Kucukislamoglu, Mustafa

    2015-04-01

    A newly series of coumarylthiazole derivatives containing aryl urea/thiourea groups were synthesized and their inhibitory effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were evaluated. The result showed that all the synthesized compounds exhibited inhibitory activity to both cholinesterases. Among them, 1-(4-(8-methoxy-2-oxo-2H-chromen-3-yl)thiazol-2-yl)-3-(4-chlorophenyl)thiourea (f8, IC50 = 4.58 μM) was found to be the most active compound against AChE, and 1-(4-fluorophenyl)-3-(4-(6-nitro-2-oxo-2H-chromen-3-yl)thiazol-2-yl)urea (e31) exhibited the strongest inhibition against BuChE with IC50 value of 4.93 μM, which was 3.5-fold more potent than that of galantamine. The selectivity of f8 and e31 were 2.64 and 0.04, respectively. In addition, the cupric reducing antioxidant capacities (CUPRAC) and ABTS cation radical scavenging abilities of the synthesized compounds were investigated for antioxidant activity. Among them, f8, f4 and f6 (IC50=1.64, 1.82 and 2.69 μM, respectively) showed significantly better ABTS cation radical scavenging ability than standard quercetin (IC50 = 15.49 μM). PMID:25706320

  6. Antidiabetic and antioxidant activities of eight medicinal mushroom species from China.

    PubMed

    Wu, Tong; Xu, Baojun

    2015-01-01

    The objective of the current study was to verify antidiabetic effects of different types of mushrooms as folk medicines in treating diabetes. The antidiabetic effects were evaluated by in vitro α-glycosidase and aldose reductase (AR) inhibitory assays and antioxidant activity assay. Ganoderma lucidum extract exhibited the best dose-dependent inhibitory activity against α-glycosidase with IC50 at 4.88 mg/mL, and also exhibited aldose reductase inhibitory potential with IC50 value of 9.87 mg/mL. Tremella fuciformis demonstrated the highest AR inhibitory activity (IC50=8.39 mg/mL). Antioxidant activities of selected mushrooms were evaluated based on the total phenolic content (TPC), total flavonoids content (TFC), and DPPH free radical scavenging activity. The result showed that G. lucidum contained the highest TPC (39.3 mg GAE/g sample extract), TFC (15.1 mg CE/g sample extract), and the strongest DPPH free radical scavenging activity (IC50=3.66 mg/mL) among the mushroom samples. PMID:25746618

  7. Anticancer activity of the Uncaria tomentosa (Willd.) DC. preparations with different oxindole alkaloid composition.

    PubMed

    Pilarski, Radosław; Filip, Beata; Wietrzyk, Joanna; Kuraś, Mieczysław; Gulewicz, Krzysztof

    2010-12-01

    The activity of Uncaria tomentosa preparations on cancer cells was studied using in vitro and in vivo models. IC (50) values were calculated for preparations with different quantitative and qualitative oxindole alkaloid composition: B/W(37) --bark extracted in water at 37 °C, B/W(b)--bark extracted in boiling water, B/50E(37) --bark extracted in 50% ethanol at 37 °C, B/E(b)--bark extracted in boiling 96% ethanol, B/96E(37) --bark extracted in 96% ethanol at 37 °C and B/SRT--bark extracted in water and dichloromethane. Generally, the results obtained showed a high correlation between the total oxindole alkaloid content (from 0.43% to 50.40% d.m.) and the antiproliferative activity of the preparations (IC(50) from >1000 μg/ml to 23.57 μg/ml). B/96E(37) and B/SRT were the most cytotoxic preparations, whereas the lowest toxicity was observed for B/W(37). B/96E(37) were shown to be active against Lewis lung carcinoma (LL/2) [IC(50) =25.06 μg/ml], cervical carcinoma (KB) [IC(50) =35.69 μg/ml] and colon adenocarcinoma (SW707) [IC(50) =49.06 μg/ml]. B/SRT was especially effective in inhibiting proliferation of cervical carcinoma (KB) [IC(50) =23.57 μg/ml], breast carcinoma (MCF-7) [IC(50) =29.86 μg/ml] and lung carcinoma (A-549) [IC(50) =40.03 μg/ml]. Further animal studies on mice bearing Lewis lung carcinoma showed significant inhibition of tumor growth by B/W(37) administered for 21 days at daily doses of 5 and 0.5 mg (p=0.0009). There were no significant changes in the cell cycles of tumor cells with the exception of cell decrease at the G₂/M phase after the administration of B/96E(37) at a daily dose of 0.5 mg and the G(1)/G(0) cells cycle arrest demonstrated after the B/SRT therapy at a daily-dose of 0.05 mg. All tested preparations were non-toxic and well tolerated. PMID:20576410

  8. Antioxidant Activity and α-Glucosidase Inhibitory Activities of the Polycondensate of Catechin with Glyoxylic Acid

    PubMed Central

    Ma, Hanjun; Liu, Benguo

    2016-01-01

    In order to investigate polymeric flavonoids, the polycondensate of catechin with glyoxylic acid (PCG) was prepared and its chemically antioxidant, cellular antioxidant (CAA) and α-glucosidase inhibitory activities were evaluated. The DPPH and ABTS radical scavenging activities and antiproliferative effect of PCG were lower than those of catechin, while PCG had higher CAA activity than catechin. In addition, PCG had very high α-glucosidase inhibitory activities (IC50 value, 2.59 μg/mL) in comparison to catechin (IC50 value, 239.27 μg/mL). Inhibition kinetics suggested that both PCG and catechin demonstrated a mixture of noncompetitive and anticompetitive inhibition. The enhanced CAA and α-glucosidase inhibitor activities of PCG could be due to catechin polymerization enhancing the binding capacity to the cellular membrane and enzymes. PMID:26960205

  9. Chemical study and antimalarial, antioxidant, and anticancer activities of Melaleuca armillaris (Sol Ex Gateau) Sm essential oil.

    PubMed

    Chabir, Naziha; Romdhane, Mehrez; Valentin, Alexis; Moukarzel, Béatrice; Marzoug, Hajer Naceur Ben; Brahim, Nadia Ben; Mars, Mohamed; Bouajila, Jalloul

    2011-11-01

    This study investigated the chemical composition (by using gas chromatography/flame ionization detection and gas chromatography/mass spectrometry, an antioxidant [1,1-diphenyl-2-picrylhydrazyl] [DPPH] radical-scavenging assay, and a 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonate [ABTS] radical cation-scavenging assay) and the antimalarial and cytotoxic activities of essential oil extracted from leaves of Melaleuca armillaris. Thirty-two components representing more than 98% of the total composition of the essential oil were identified. The main components were 1,8-cineole (85.8%), camphene (5.05%), and α-pinene (1.95%). The antioxidant activity by ABTS assay showed a mean (± standard deviation) 50% inhibitory concentration (IC(50)) value of 247.3 ± 3.9 mg/L, and the DPPH assay yielded an IC(50) value of 2183.6 ± 44.3 mg/L. The antimalarial study indicated that the essential oil had mild activity against the chloroquine-resistant Plasmodium falciparum FcB1 strain (IC(50), 27 ± 2 mg/L). The cytotoxic activity of this essential oil was tested against MCF7 human breast cancer cells and was found to be high (IC(50), 12 ± 1 mg/L). PMID:21476932

  10. Anti-proliferative lichen compounds with inhibitory activity on 12(S)-HETE production in human platelets.

    PubMed

    Bucar, F; Schneider, I; Ogmundsdóttir, H; Ingólfsdóttir, K

    2004-11-01

    Several lichen compounds, i.e. lobaric acid (1), a beta-orcinol depsidone from Stereocaulon alpinum L., (+)-protolichesterinic acid (2), an aliphatic alpha-methylene-gamma-lactone from Cetraria islandica Laur. (Parmeliaceae), (+)-usnic acid (3), a dibenzofuran from Cladonia arbuscula (Wallr.) Rabenh. (Cladoniaceae), parietin (4), an anthraquinone from Xanthoria elegans (Link) Th. Fr. (Calaplacaceae) and baeomycesic acid (5), a beta-orcinol depside isolated from Thamnolia vermicularis (Sw.) Schaer. var. subuliformis (Ehrh.) Schaer. were tested for inhibitory activity on platelet-type 12(S)-lipoxygenase using a cell-based in vitro system in human platelets. Lobaric acid (1) and (+)-protolichesterinic acid (2) proved to be pronounced inhibitors of platelet-type 12(S)-lipoxygenase, whereas baeomycesic acid (5) showed only weak activity (inhibitory activity at a concentration of 100 microg/ml: (1) 93.4+/-6.62%, (2) 98,5+/-1.19%, 5 14.7+/-2.76%). Usnic acid (3) and parietin (4) were not active at this concentration. 1 and 2 showed a clear dose-response relationship in the range of 3.33-100 microg/ml. According to the calculated IC50 values the highest inhibitory activity was observed for the depsidone 1 (IC50 = 28.5 microM) followed by 2 (IC50 = 77.0 microM). The activity of 1 was comparable to that of the flavone baicalein, which is known as a selective 12(S)-lipoxygenase inhibitor (IC50 = 24.6 microM). PMID:15636173

  11. In vitro cytotoxic activity of extracts and isolated constituents of Salvia leriifolia Benth. against a panel of human cancer cell lines.

    PubMed

    Tundis, Rosa; Loizzo, Monica R; Menichini, Federica; Bonesi, Marco; Colica, Carmela; Menichini, Francesco

    2011-06-01

    In the course of recent efforts to identify new potential antiproliferative active principles, Salvia leriifolia extracts and isolated constituents were evaluated for their cytotoxic activity against a panel of human cancer cell lines, including renal adenocarcinoma (ACHN), amelanotic melanoma (C32), colorectal adenocarcinoma (Caco-2), lung large cell carcinoma (COR-L23), malignant melanoma (A375), lung carcinoma (A549), and hepatocellular carcinoma (Huh-7D12) cells. The hexane and CH(2) Cl(2) extracts showed the strongest cytotoxic activity against the C32 cell line with IC(50) values of 11.2 and 13.6 μg/ml, respectively, and the AcOEt extract was the most active extract against the COR-L23 cell line (IC(50) of 20.9 μg/ml). Buchariol, a sesquiterpene obtained by biofractionation of the CH(2) Cl(2) extract, exhibited a higher activity than the positive control vinblastine against the C32 and A549 cell lines (IC(50) values of 2.1 and 12.6 μM, resp.). Interesting results were also obtained for naringenin, a flavonoid isolated from the AcOEt extract, which exhibited a strong cytotoxic activity against the C32, LNCaP, and COR-L23 cell lines (IC(50) values of 2.2, 7.7, and 33.4 μM, resp.), compared to vinblastine (IC(50) values of 3.3, 32.2, 50.0 μM, resp.). None of the tested compounds affected the proliferation of skin fibroblasts (142BR), suggesting a selective activity against tumor cells. PMID:21674787

  12. Anti-allergic activity of some selected plants in the Zingiberaceae family.

    PubMed

    Tewtrakul, Supinya; Subhadhirasakul, Sanan

    2007-02-12

    Ethanolic and water extracts, together with volatile oils from the rhizomes of six selected Zingiberaceous plants, including Curcuma mangga, Kaempferia galanga, Kaempferia parviflora, Zingiber cassumunar, Zingiber officinale and Zingiber zerumbet were investigated for their anti-allergic activities using a RBL-2H3 cell line. The ethanolic (EtOH) extract of Kaempferia parviflora exhibited the most potent anti-allergic effect against antigen-induced beta-hexosaminidase release as a marker of degranulation in RBL-2H3 cells, with an IC(50) value of 10.9 microg/ml, followed by Zingiber cassumunar (EtOH, IC(50)=12.9 microg/ml) and Curcuma mangga (water, IC(50)=36.1 microg/ml). The volatile oils of these six plants were apparently inactive (IC(50)>100 microg/ml). The crude extracts were also tested on beta-hexosaminidase activity to clarify whether their effects were due to the inhibition of enzyme activity or of degranulation. As a result, the plant extracts were inactive against the enzyme activity of beta-hexosaminidase. These findings support the use in Thai traditional medicine of these selected Zingiberaceous plants, especially Kaempferia parviflora and Zingiber cassumunar, for treatment of allergy and allergic-related diseases. PMID:16978816

  13. Biochemical and antitumor activity of trimidox, a new inhibitor of ribonucleotide reductase.

    PubMed

    Szekeres, T; Gharehbaghi, K; Fritzer, M; Woody, M; Srivastava, A; van't Riet, B; Jayaram, H N; Elford, H L

    1994-01-01

    Trimidox (3,4,5-trihydroxybenzamidoxime), a newly synthesized analog of didox (N,3,4-trihydroxybenzamide) reduced the activity of ribonucleotide reductase (EC 1.17.4.1) in extracts of L1210 cells by 50% (50% growth-inhibitory concentration, IC50) at 5 microM, whereas hydroxyurea, the only ribonucleotide reductase inhibitor in clinical use, exhibited an IC50 of 500 microM. Ribonucleotide reductase activity was also measured in situ by incubating L1210 cells for 24 h with trimidox at 7.5 microM, a concentration that inhibits cell proliferation by 50% (IC50) or at 100 microM for 2 h; these concentrations resulted in a decrease in enzyme activity to 22% and 50% of the control value, respectively. Trimidox and hydroxyurea were cytotoxic to L1210 cells with IC50 values of 7.5 and 50 microM, respectively. Versus ribonucleotide reductase, trimidox and hydroxyurea yielded IC50 values of 12 and 87 microM, respectively. A dose-dependent increase in life span was observed in mice bearing intraperitoneally transplanted L1210 tumors. Trimidox treatment (200 mg/kg; q1dx9) significantly increased the life span of mice bearing L1210 leukemia (by 82% in male mice and 112% in female mice). The anti-tumor activity appeared more pronounced in female mice than in male mice. Viewed in concert, these findings suggest that trimidox is a new and potent inhibitor of ribonucleotide reductase and that it is a promising candidate for the chemotherapy of cancer in humans. PMID:8174204

  14. Phenolic contents, antioxidant and cytotoxic activities of Elaeocarpus floribundus Blume.

    PubMed

    Utami, Rahayu; Khalid, Nurhasniza; Sukari, Mohd Aspollah; Rahmani, Mawardi; Abdul, Ahmad Bustaman; Dachriyanus

    2013-03-01

    Elaeocarpus floribundus is higher plant that has been used as traditional medicine for treating several diseases. There is no previous report on phytochemicals and bioactivity studies of this species. In this investigation, triterpenoids friedelin, epifriedelanol and β-sitosterol were isolated from its leaves and stem bark. Determination of total phenolic content of methanolic extract of leaves and stem bark was carried out using Folin-Ciocalteu reagent. All extracts and isolated compounds were subjected to screening of antioxidant activity using DPPH free radical scavenging method and cytotoxic activities by MTT assay towards human T4 lymphoblastoid (CEM-SS) and human cervical (HeLa) cancer cells. In the total phenolic content determination, methanolic extract of leaves gave higher value of 503.08±16.71 mg GAE/g DW than stem bark with value of 161.5±24.81 mg GAE/g DW. Polar extracts of leaves and stem bark possessed promising antioxidant activity with methanol extract of stem bark exhibited strongest activity with IC50 value of 7.36±0.01 μg/ml. In the cytotoxic activity assay, only chloroform extract of leaves showed significant activity with IC50 value of 25.6±0.06 μg/ml against CEM-SS cancer cell, while friedelin and epifriedelanol were found to be active against the two cancer cells with IC50 values ranging from 3.54 to 11.45 μg/ml. PMID:23455191

  15. The Antiviral Activity of Approved and Novel Drugs against HIV-1 Mutations Evaluated under the Consideration of Dose-Response Curve Slope

    PubMed Central

    Chang, Shuai; Zhuang, Daomin; Guo, Wei; Li, Lin; Zhang, Wenfu; Liu, Siyang; Li, Hanping; Liu, Yongjian; Bao, Zuoyi; Han, Jingwan

    2016-01-01

    Objectives This study was designed to identify common HIV-1 mutation complexes affecting the slope of inhibition curve, and to propose a new parameter incorporating both the IC50 and the slope to evaluate phenotypic resistance. Methods Utilizing site-directed mutagenesis, we constructed 22 HIV-1 common mutation complexes. IC50 and slope of 10 representative approved drugs and a novel agent against these mutations were measured to determine the resistance phenotypes. The values of new parameter incorporating both the IC50 and the slope of the inhibition curve were calculated, and the correlations between parameters were assessed. Results Depending on the class of drug, there were intrinsic differences in how the resistance mutations affected the drug parameters. All of the mutations resulted in large increases in the IC50s of nucleoside reverse transcriptase inhibitors. The effects of the mutations on the slope were the most apparent when examining their effects on the inhibition of non-nucleoside reverse transcriptase inhibitors and protease inhibitors. For example, some mutations, such as V82A, had no effect on IC50, but reduced the slope. We proposed a new concept, termed IIPatoxic, on the basis of IC50, slope and the maximum limiting concentrations of the drug. The IIPatoxic values of 10 approved drugs and 1 novel agent were calculated, and were closely related to the IIPmax values (r > 0.95, p < 0.001). Conclusions This study confirms that resistance mutations cannot be accurately assessed by IC50 alone, because it tends to underestimate the degree of resistance. The slope parameter is of very importance in the measurement of drug resistance and the effect can be applied to more complex patterns of resistance. This is the most apparent when testing the effects of the mutations on protease inhibitors activity. We also propose a new index, IIPatoxic, which incorporates both the IC50 and the slope. This new index could complement current IIP indices, thereby

  16. Biological activities of aqueous extract from Cinnamomum porrectum

    NASA Astrophysics Data System (ADS)

    Farah, H. Siti; Nazlina, I.; Yaacob, W. A.

    2013-11-01

    A study was carried out to evaluate biological activities of an extract obtained from Cinnamomum porrectum under reflux using water. Aqueous extract of Cinnamomum porrectum was tested for antibacterial activity against six Gram-positive and eight Gram-negative bacteria as well as MRSA. The results confirmed that the aqueous extract of Cinnamomum porrectum was bactericidal. Cytotoxic tests on Vero cell culture revealed that Cinnamomum porrectum was non-toxic which IC50 value higher than 0.02 mg/mL. Antiviral activity was tested based on the above IC50 values together with the measured EC50 values to obtain Therapeutic Index. The result showed that Cinnamomum porrectum has the ability to inhibit viral replication of HSV-1 in Vero cells.

  17. Cytotoxic activity of Thai medicinal plants against human cholangiocarcinoma, laryngeal and hepatocarcinoma cells in vitro

    PubMed Central

    2010-01-01

    Background Cholangiocarcinoma is a serious public health in Thailand with increasing incidence and mortality rates. The present study aimed to investigate cytotoxic activities of crude ethanol extracts of a total of 28 plants and 5 recipes used in Thai folklore medicine against human cholangiocarcinoma (CL-6), human laryngeal (Hep-2), and human hepatocarcinoma (HepG2) cell lines in vitro. Methods Cytotoxic activity of the plant extracts against the cancerous cell lines compared with normal cell line (renal epithelial cell: HRE) were assessed using MTT assay. 5-fluorouracil was used as a positive control. The IC50 (concentration that inhibits cell growth by 50%) and the selectivity index (SI) were calculated. Results The extracts from seven plant species (Atractylodes lancea, Kaempferia galangal, Zingiber officinal, Piper chaba, Mesua ferrea, Ligusticum sinense, Mimusops elengi) and one folklore recipe (Pra-Sa-Prao-Yhai) exhibited promising activity against the cholangiocarcinoma CL-6 cell line with survival of less than 50% at the concentration of 50 μg/ml. Among these, the extracts from the five plants and one recipe (Atractylodes lancea, Kaempferia galangal, Zingiber officinal, Piper chaba, Mesua ferrea, and Pra-Sa-Prao-Yhai recipe) showed potent cytotoxic activity with mean IC50 values of 24.09, 37.36, 34.26, 40.74, 48.23 and 44.12 μg/ml, respectively. All possessed high activity against Hep-2 cell with mean IC50 ranging from 18.93 to 32.40 μg/ml. In contrast, activity against the hepatoma cell HepG2 varied markedly; mean IC50 ranged from 9.67 to 115.47 μg/ml. The only promising extract was from Zingiber officinal (IC50 = 9.67 μg/ml). The sensitivity of all the four cells to 5-FU also varied according to cell types, particularly with CL-6 cell (IC50 = 757 micromolar). The extract from Atractylodes lancea appears to be both the most potent and most selective against cholangiocarcinoma (IC50 = 24.09 μg/ml, SI = 8.6). Conclusions The ethanolic extracts from

  18. Quercus infectoria galls possess antioxidant activity and abrogates oxidative stress-induced functional alterations in murine macrophages.

    PubMed

    Kaur, Gurpreet; Athar, Mohammad; Alam, M Sarwar

    2008-02-15

    The present study reports the antioxidant activity of ethanolic extract of Quercus infectoria galls. The antioxidant potency of galls was investigated employing several established in vitro model systems. Their protective efficacy on oxidative modulation of murine macrophages was also explored. Gall extract was found to contain a large amount of polyphenols and possess a potent reducing power. HPTLC analysis of the extract suggested it to contain 19.925% tannic acid (TA) and 8.75% gallic acid (GA). The extract potently scavenged free radicals including DPPH (IC(50)~0.5 microg/ml), ABTS (IC(50)~1 microg/ml), hydrogen peroxide (H(2)O(2)) (IC(50)~2.6 microg/ml) and hydroxyl (*OH) radicals (IC(50)~6 microg/ml). Gall extract also chelated metal ions and inhibited Fe(3+) -ascorbate-induced oxidation of protein and peroxidation of lipids. Exposure of rat peritoneal macrophages to tertiary butyl hydroperoxide (tBOOH) induced oxidative stress in them and altered their phagocytic functions. These macrophages showed elevated secretion of lysosomal hydrolases, and attenuated phagocytosis and respiratory burst. Activity of macrophage mannose receptor (MR) also diminished following oxidant exposure. Pretreatment of macrophages with gall extract preserved antioxidant armory near to control values and significantly protected against all the investigated functional mutilations. MTT assay revealed gall extract to enhance percent survival of tBOOH exposed macrophages. These results indicate that Q. infectoria galls possess potent antioxidant activity, when tested both in chemical as well as biological models. PMID:18076871

  19. Antimicrobial and antiproliferative activity of Peucedanum nebrodense (Guss.) Strohl.

    PubMed

    Schillaci, D; Venturella, F; Venuti, F; Plescia, F

    2003-07-01

    Acetone extract of Peucedanum nebrodense (Guss.) Strohl., a rare endemic species from the Madonie mountains (Sicily), was tested in vitro for its antimicrobial activity against bacterial reference strains and antiproliferative activity against K562 (human chronic myelogenous leukemia), HL-60 (human leukemia) and L1210 (murine leukemia) cell lines. The acetone extract showed antiproliferative IC50 values in the range of 14-0.27 microg/ml. PMID:12787961

  20. Synthesis and antitumor activity evaluation of lamiridosin A derivatives.

    PubMed

    Yang, Yan-Xia; Yan, Jian-Wei; Yan, Fu-Lin; Yin, Yan-Yan; Zhuang, Fang-Fang; Ji, Zi-Yang

    2016-01-01

    A series of lamiridosin A derivatives were synthesized through simple procedures. Their antitumor activities were evaluated against EC9706, MGC803, and B16 cell lines in vitro. Several compounds showed potent antitumor activity, especially compound 10, with IC50 value of 2.36 μmol/L against MGC803 cell lines, is more potent than marketed positive drug 5-fluorouridine (5-FU). PMID:26757858

  1. A facile ionic liquid promoted synthesis, cholinesterase inhibitory activity and molecular modeling study of novel highly functionalized spiropyrrolidines.

    PubMed

    Almansour, Abdulrahman I; Kumar, Raju Suresh; Arumugam, Natarajan; Basiri, Alireza; Kia, Yalda; Ali, Mohamed Ashraf; Farooq, Mehvish; Murugaiyah, Vikneswaran

    2015-01-01

    A series of novel dimethoxyindanone embedded spiropyrrolidines were synthesized in ionic liquid, [bmim]Br and were evaluated for their inhibitory activities towards cholinesterases. Among the spiropyrrolidines, compound 4f exhibited the most potent activity with an IC50 value of 1.57 µM against acethylcholinesterase (AChE). Molecular docking simulation for the most active compound was employed with the aim of disclosing its binding mechanism to the active site of AChE receptor. PMID:25642838

  2. Design, synthesis and antibacterial activity of isatin derivatives as FtsZ inhibitors

    NASA Astrophysics Data System (ADS)

    Lian, Zhi-Min; Sun, Juan; Zhu, Hai-Liang

    2016-08-01

    Seven isatin derivatives have been designed, and their chemical structures were characterized by single crystal X-ray diffraction studies, 1H NMR, MS, and elemental analysis. Structural stabilization followed by intramolecular as well as intermolecular H-bonds makes these molecules as perfect examples in molecular recognition with self-complementary donor and acceptor units within a single molecule. These compounds were evaluated for antimicrobial activities. Docking simulations have been performed to position compounds into the FtsZ active site to determine their probable binding models. All of the compounds exhibited better antibacterial activities. Interestingly, compound 5c and 5d exhibited better antibacterial activities with IC50 values of 0.03 and 0.05 μmol/mL against Staphylococcus aureus, respectively. Compound 5g displays antibacterial activity with IC50 values of 0.672 and 0.830 μmol/mL against Escherichia coli and Pseudomonas aeruginosa, respectively.

  3. Screening of African medicinal plants for antimicrobial and enzyme inhibitory activity.

    PubMed

    Tshibangu, Jeannette Ndaya; Chifundera, Kusamba; Kaminsky, Ronald; Wright, Anthony David; König, Gabriele Maria

    2002-04-01

    Seven plant species, belonging to different families, were collected in the eastern part of the Republic of Congo (Kivu) based on ethnopharmacological information. Their dichloromethane and methanolic extracts were tested for biological activity. Five of the seven collected plants exhibited antiplasmodial activity with IC(50) values ranging from 1.1 to 9.8 microg/ml. The methanolic extract of Cissampelos mucronata was the most active one showing activity against chloroquine sensitive (D6) and chloroquine resistant (W2) Plasmodium falciparum strains with IC(50) values of 1.5 and 1.1 microg/ml, respectively. Additionally, this extract significantly inhibited the enzyme tyrosine kinase p56(lck) (TK). The dichloromethane extract of Amorphophallus bequaertii inhibited the growth of Mycobacterium tuberculosis with a MIC of 100 microg/ml and the methanolic extract of Rubus rigidus inhibited the activity of both enzymes HIV1-reverse transcriptase (HIV1-RT) and TK p56(lck). PMID:11891084

  4. Antimycobacterial and HIV-1 Reverse Transcriptase Activity of Julianaceae and Clusiaceae Plant Species from Mexico

    PubMed Central

    Gómez-Cansino, Rocio; Espitia-Pinzón, Clara Inés; Campos-Lara, María Guadalupe; Guzmán-Gutiérrez, Silvia Laura; Segura-Salinas, Erika; Echeverría-Valencia, Gabriela; Torras-Claveria, Laura; Cuevas-Figueroa, Xochitl Marisol; Reyes-Chilpa, Ricardo

    2015-01-01

    The extracts of 14 Julianaceae and 5 Clusiaceae species growing in Mexico were tested in vitro (50 µg/mL) against Mycobacterium tuberculosis H37Rv and HIV reverse transcriptase (HIV-RT). The Julianaceae bark and leaf extracts inhibited M. tuberculosis (>84.67%) and HIV-RT (<49.89%). The Clusiaceae leaves extracts also inhibited both targets (>58.3% and >67.6%), respectively. The IC50 values for six selected extracts and their cytotoxicity (50 µg/mL) to human macrophages were then determined. Amphipterygium glaucum, A. molle, and A. simplicifolium fairly inhibited M. tuberculosis with IC50 of 1.87–2.35 µg/mL; but their IC50 against HIV-RT was 59.25–97.83 µg/mL. Calophyllum brasiliense, Vismia baccifera, and Vismia mexicana effect on M. tuberculosis was noteworthy (IC50 3.02–3.64 µg/mL) and also inhibited RT-HIV (IC50 26.24–35.17 µg/mL). These 6 extracts (50 µg/mL) presented low toxicity to macrophages (<23.8%). The HPLC profiles of A. glaucum, A. molle, and A. simplicifolium indicated that their antimycobacterial activity cannot be related to masticadienonic, 3α, or 3β-hydromasticadienonic acids, suggesting that other compounds may be responsible for the observed activity or this might be a synergy result. The anti-HIV-RT and antimycobacterial activities induced by C. brasiliense can be attributed to the content of calanolides A, B, as well as soulatrolide. PMID:25983849

  5. Antioxidant Activity in the Extracts of Two Edible Aroids

    PubMed Central

    Mandal, P.; Misra, T. K.; Singh, I. D.

    2010-01-01

    Two neglected species of Araceae, Alocasia macrorhiza (Linn.) G. Don and Alocasia fornicata (Roxb.) Schott are important as food and ethno medicine in Asia and Africa. Their bioefficacy is documented in the Ayurveda. The solvent extracts of different edible parts of these two species like rhizomes, leaves, roots and stolons were screened for in vitro antioxidant properties using standard procedures. The successive extracts in hexane, benzene, toluene, chloroform, diethyl ether, ethyl acetate and water fraction exhibited IC50 values in the following order, roots>rhizome>leaves for Alocasia macrorhiza and leaves>stolon for Alocasia fornicate, respectively in 2,2-diphenyl-1-picryl hydrazyl antioxidant inhibition assay. Maximum antioxidant activity was observed in diethyl ether extracts for both species. The IC50 values were comparable with those of quercetine and ascorbic acid as standards. These results suggest that the two aroid species have antioxidant activity in their edible parts and should be extracted using diethyl ether solvent. PMID:20582198

  6. Antioxidant activity in the extracts of two edible aroids.

    PubMed

    Mandal, P; Misra, T K; Singh, I D

    2010-01-01

    Two neglected species of Araceae, Alocasia macrorhiza (Linn.) G. Don and Alocasia fornicata (Roxb.) Schott are important as food and ethno medicine in Asia and Africa. Their bioefficacy is documented in the Ayurveda. The solvent extracts of different edible parts of these two species like rhizomes, leaves, roots and stolons were screened for in vitro antioxidant properties using standard procedures. The successive extracts in hexane, benzene, toluene, chloroform, diethyl ether, ethyl acetate and water fraction exhibited IC(50) values in the following order, roots>rhizome>leaves for Alocasia macrorhiza and leaves>stolon for Alocasia fornicate, respectively in 2,2-diphenyl-1-picryl hydrazyl antioxidant inhibition assay. Maximum antioxidant activity was observed in diethyl ether extracts for both species. The IC(50) values were comparable with those of quercetine and ascorbic acid as standards. These results suggest that the two aroid species have antioxidant activity in their edible parts and should be extracted using diethyl ether solvent. PMID:20582198

  7. Antiparasitic activity of C-geranyl flavonoids from Mimulus bigelovii.

    PubMed

    Salem, Manar M; Capers, Jeffrey; Rito, Shawn; Werbovetz, Karl A

    2011-08-01

    Bioactivity-directed fractionation of the MeOH fraction of the extract of Mimulus bigelovii by means of an axenic Leishmania amastigote assay and chromatographic techniques resulted in the isolation of four C-geranyl flavanones, diplacone (1), 3'-O-methyldiplacone (2), 4'-O-methyldiplacone (3), 3'-O-methyldiplacol (4), together with a geranylated flavone, cannflavin A (5). These compounds were separated from M. bigelovii for the first time. All compounds showed moderate antileishmanial activity against axenic Leishmania donovani amastigotes with IC(50) values ranging from 4.8 to 14.6 μg/mL. The compounds were also tested against the related kinetoplastid parasite Trypanosoma brucei brucei and they showed activity with IC(50) values ranging from 1.4 to 7.2 μg/mL. PMID:21796699

  8. In vitro antitrypanosomal activity of ethnopharmacologically selected Beninese plants.

    PubMed

    Hoet, Sara; Opperdoes, Frederik; Brun, Reto; Adjakidjé, Victor; Quetin-Leclercq, Joëlle

    2004-03-01

    The in vitro antitrypanosomal activity of methylene chloride, methanol and aqueous extracts of the leaves and twigs of five plant species traditionally used in Benin for the treatment of sleeping sickness were evaluated on Trypanosoma brucei brucei and their selectivity was analysed on Leishmania mexicana mexicana and J774 macrophage-like murine cells. The results showed that the four most active extracts had MIC values < or =19 microg/ml (Hymenocardia acida twig and leaf, Strychnos spinosa leaf, Trichilia emetica leaf methylene chloride extracts). All these extracts had a lower activity on L. m. mexicana and J774 cells. Determination of the IC50 values of the methylene chloride leaf extracts on two strains of trypanosomes (T. b. brucei and T. b. rhodesiense) and two mammalian cell lines (L6 and J774 cells) showed that all extracts possessed some antitrypanosomal activity with IC50's ranging from 1.5 to 39 microg/ml. All were also toxic to the mammalian cells, but usually with higher IC50's. The only exception was the S. spinosa methylene chloride leaf extract which had no toxicity on J774 cells. Although tannins have been identified in most of the species studied, they could not be detected in the most active extracts, just as alkaloids. The presence of flavonoids and quinones may at least in part explain the observed activities of some of the active extracts. PMID:15036465

  9. Inhibitory activities of pancreatic lipase and phosphodiesterase from Korean medicinal plant extracts.

    PubMed

    Lee, Yun Mi; Kim, Young Sook; Lee, Youngseop; Kim, Junghyun; Sun, Hang; Kim, Joo Hwan; Kim, Jin Sook

    2012-05-01

    To find new pancreatic lipase (triacylglycerol acylhydrolase, EC 3.1.1.3) inhibitors from natural products, 61 medicinal plants from Korea were screened for their antilipase activity for prevention of obesity. Dried and powdered plants were extracted three times with EtOH and extracts were obtained by removal of the solvent in vacuo. Lipase activity was determined by measuring the hydrolysis of p-nitrophenyl butyrate to p-nitrophenol. Also, the inhibitory effect was measured on phosphodiesterase (PDE), another therapeutic target for obesity. Of the extracts tested, Sorbus commixta (stem, leaf) and Viscum album (whole plant) exhibited antilipase activity (with IC(50) values of 29.6 µg/mL and 33.3 µg/mL, respectively) and only anti-PDE activity (IC(50) values of 20.08 µg/mL and 35.15 µg/mL, respectively). PMID:22069182

  10. Anti-inflammatory and cytotoxic activities of Bursera copallifera

    PubMed Central

    Columba-Palomares, M. F. María C.; Villareal, Dra. María L.; Acevedo Quiroz, M. C. Macdiel E.; Marquina Bahena, M. C. Silvia; Álvarez Berber, Dra. Laura P.; Rodríguez-López, Dra. Verónica

    2015-01-01

    Background: The plant species Bursera copallifera (DC) bullock is used in traditional medicine to treat inflammation. The leaves of this plant can be prepared as an infusion to treat migraines, bronchitis, and dental pain Objective: The purpose of this study was to determine the anti-inflammatory and cytotoxic activities of organic extracts from the stems, stem bark, and leaves of B. copallifera, which was selected based on the knowledge of its traditional use. Materials and Methods: We evaluated the ability of extracts to inhibit mouse ear inflammation in response to topical application of 12-O tetradecanoylphorbol-13-acetate. The extracts with anti-inflammatory activity were evaluated for their inhibition of pro-inflammatory enzymes. In addition, the in vitro cytotoxic activities of the organic extracts were evaluated using the sulforhodamine B assay. Results: The hydroalcoholic extract of the stems (HAS) exhibited an anti-inflammatory activity of 54.3% (0.5 mg/ear), whereas the anti-inflammatory activity of the dichloromethane-methanol extract from the leaves (DMeL) was 55.4% at a dose of 0.1 mg/ear. Methanol extract from the leaves (MeL) showed the highest anti-inflammatory activity (IC50 = 4.4 μg/mL), hydroalcoholic extract of leaves, and DMeL also reduce the enzyme activity, (IC50 = 6.5 μg/mL, IC50 = 5.7 μg/mL), respectively, from stems HAS exhibit activity at the evaluated concentrations (IC50 =6.4 μg/mL). The hydroalcoholic extract of the stems exhibited the highest cytotoxic activity against a breast adenocarcinoma cell line (MCF7, IC50 = 0.90 μg/mL), whereas DMeL exhibited an IC50 value of 19.9 μg/mL. Conclusion: In conclusion, extracts from leaves and stems inhibited cyclooxygenase-1, which is the target enzyme for nonsteroidal anti inflammatory drugs, and some of these extracts demonstrated substantial antiproliferative effects against the MCF7 cell line. These results validate the traditional use of B. copallifera. PMID:26664022

  11. Helichrysum gymnocephalum essential oil: chemical composition and cytotoxic, antimalarial and antioxidant activities, attribution of the activity origin by correlations.

    PubMed

    Afoulous, Samia; Ferhout, Hicham; Raoelison, Emmanuel Guy; Valentin, Alexis; Moukarzel, Béatrice; Couderc, François; Bouajila, Jalloul

    2011-01-01

    Helichrysum gymnocephalum essential oil (EO) was prepared by hydrodistillation of its leaves and characterized by GC-MS and quantified by GC-FID. Twenty three compounds were identified. 1,8-Cineole (47.4%), bicyclosesquiphellandrene (5.6%), γ-curcumene (5.6%), α-amorphene (5.1%) and bicyclogermacrene (5%) were the main components. Our results confirmed the important chemical variability of H. gymnocephalum. The essential oil was tested in vitro for cytotoxic (on human breast cancer cells MCF-7), antimalarial (Plasmodium falciparum: FcB1-Columbia strain, chloroquine-resistant) and antioxidant (ABTS and DPPH assays) activities. H. gymnocephalum EO was found to be active against MCF-7 cells, with an IC(50) of 16 ± 2 mg/L. The essential oil was active against P. falciparum (IC(50) = 25 ± 1 mg/L). However, the essential oil exhibited a poor antioxidant activity in the DPPH (IC(50) value > 1,000 mg/L) and ABTS (IC(50) value = 1,487.67 ± 47.70 mg/L) assays. We have reviewed the existing results on the anticancer activity of essential oils on MCF-7 cell line and on their antiplasmodial activity against the P. falciparum. The aim was to establish correlations between the identified compounds and their biological activities (antiplasmodial and anticancer). β-Selinene (R² = 0.76), α-terpinolene (R² = 0.88) and aromadendrene (R² = 0.90) presented a higher relationship with the anti-cancer activity. However, only calamenene (R² = 0.70) showed a significant correlation for the antiplasmodial activity. PMID:21959299

  12. Acetylcholinesterase inhibition, antioxidant activity and toxicity of Peumus boldus water extracts on HeLa and Caco-2 cell lines.

    PubMed

    Falé, P L; Amaral, F; Amorim Madeira, P J; Sousa Silva, M; Florêncio, M H; Frazão, F N; Serralheiro, M L M

    2012-08-01

    This work aimed to study the inhibition on acetylcholinesterase activity (AChE), the antioxidant activity and the toxicity towards Caco-2 and HeLa cells of aqueous extracts of Peumus Boldus. An IC(50) value of 0.93 mg/mL, for AChE inhibition, and EC(50) of 18.7 μg/mL, for the antioxidant activity, was determined. This activity can be attributed to glycosylated flavonoid derivatives detected, which were the main compounds, although boldine and other aporphine derivatives were also present. No changes in the chemical composition or the biochemical activities were found after gastrointestinal digestion. Toxicity of P. boldus decoction gave an IC(50) value 0.66 mg/mL for HeLa cells, which caused significant changes in the cell proteome profile. PMID:22617353

  13. Plants from Brazilian Cerrado with Potent Tyrosinase Inhibitory Activity

    PubMed Central

    Souza, Paula Monteiro; Elias, Silvia Taveira; Simeoni, Luiz Alberto; de Paula, José Elias; Gomes, Sueli Maria; Guerra, Eliete Neves Silva; Fonseca, Yris Maria; Silva, Elton Clementino; Silveira, Dâmaris; Magalhães, Pérola Oliveira

    2012-01-01

    The increased amount of melanin leads to skin disorders such as age spots, freckles, melasma and malignant melanoma. Tyrosinase is known to be the key enzyme in melanin production. Plants and their extracts are inexpensive and rich resources of active compounds that can be utilized to inhibit tyrosinase as well as can be used for the treatment of dermatological disorders associated with melanin hyperpigmentation. Using in vitro tyrosinase inhibitory activity assay, extracts from 13 plant species from Brazilian Cerrado were evaluated. The results showed that Pouteria torta and Eugenia dysenterica extracts presented potent in vitro tyrosinase inhibition compared to positive control kojic acid. Ethanol extract of Eugenia dysenterica leaves showed significant (p<0.05) tyrosinase inhibitory activity exhibiting the IC50 value of 11.88 µg/mL, compared to kojic acid (IC50 value of 13.14 µg/mL). Pouteria torta aqueous extract leaves also showed significant inhibitory activity with IC50 value of 30.01 µg/mL. These results indicate that Pouteria torta and Eugenia dysenterica extracts and their isolated constituents are promising agents for skin-whitening or antimelanogenesis formulations. PMID:23173036

  14. In vitro antiplasmodial, antiamoebic, and cytotoxic activities of a series of bisbenzylisoquinoline alkaloids.

    PubMed Central

    Marshall, S J; Russell, P F; Wright, C W; Anderson, M M; Phillipson, J D; Kirby, G C; Warhurst, D C; Schiff, P L

    1994-01-01

    Twenty-four bisbenzylisoquinoline alkaloids were screened for antiplasmoidal, antiamoebic, and cytotoxic activities by use of in vitro microtests. Eight of the alkaloids had antiplasmodial activity, with a 50% inhibitory concentration (IC50) of less than 1 microM against a multidrug-resistant strain of Plasmodium falciparum (chloroquine had an IC50 of 0.2 microM). The three alkaloids most active against Entamoeba histolytica, aromoline, isotrilobine, and insularine, had IC50s of 5 to 11.1 microM (metronidazole had an IC50 of 1.87 microM). None of the 24 bisbenzylisoquinoline alkaloids exhibited significant cytotoxicity against the KB cell line, the most toxic being berbamine, with an IC50 of 17.8 microM (the IC50 of podophyllotoxin was 0.008 microM). Bisbenzylisoquinoline alkaloids merit further investigation as potential novel antimalarial agents. PMID:8141587

  15. The Inhibitory Effect of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) on the Monophenolase and Diphenolase Activities of Mushroom Tyrosinase

    PubMed Central

    Sato, Kazuomi; Toriyama, Masaru

    2011-01-01

    In the present work, we investigated the effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the monophenolase and diphenolase activity of mushroom tyrosinase. The results showed that diflunisal and indomethacin inhibited both monophenolase and diphenolase activity. For monophenolase activity, the lag time was extended in the presence of diflunisal. In the presence of indomethacin, the lag time did not change. IC50 values of monophenolase activity were estimated to be 0.112 mM (diflunisal) and 1.78 mM (indomethacin). Kinetic studies of monophenolase activity revealed that both diflunisal and indomethacin were non-competitive inhibitors. For diphenolase activity, IC50 values were estimated to be 0.197 mM (diflunisal) and 0.509 mM (indomethacin). Diflunisal and indomethacin were also found to be non-competitive diphenolase inhibitors. PMID:21747720

  16. Cytotoxic and anti-tumor activities of lignans from the seeds of Vietnamese nutmeg Myristica fragrans.

    PubMed

    Thuong, Phuong Thien; Hung, Tran Manh; Khoi, Nguyen Minh; Nhung, Hoang Thi My; Chinh, Nguyen Thi; Quy, Nguyen Thi; Jang, Tae Su; Na, Minkyun

    2014-03-01

    Four lignans, meso-dihydroguaiaretic acid (DHGA), macelignan, fragransin A2 and nectandrin B, were isolated from the seeds of Myristica fragrans (Vietnamese nutmeg) and investigated for their cytotoxic activity against eight cancer cell lines. Of these, DHGA exhibited potent cytotoxicity against H358 with IC50 value of 10.1 μM. In addition, DHGA showed antitumor activity in allogeneic tumor-bearing mice model. PMID:23877238

  17. Highly oxygenated triterpenoids from the roots of Schisandra chinensis and their anti-inflammatory activities.

    PubMed

    Song, Qiu-Yan; Gao, Kun; Nan, Zhi-Biao

    2016-01-01

    A new highly oxygenated triterpenoid, schinchinenlactone D (1), and three known compounds (2-4) were isolated from the roots of Schisandra chinensis. Their structures were determined by combining the spectroscopic analysis with the theoretical computations. The anti-inflammatory activities of compounds 1-4 were evaluated, and compound 3 exhibits the most significant activity in the inhibition of NO production with an IC50 value of 10.6 μM. PMID:26313467

  18. Evaluation of Antiplasmodial activity of extracts and constituents from Ampelozizyphus amazonicus

    PubMed Central

    do Carmo, Dominique F. M.; Amaral, Ana Claudia F.; Machado, Marta; Lopes, Dinora; Echevarria, Aurea; Rosário, Virgílio E.; Silva, Jefferson Rocha de A.

    2015-01-01

    Background: Ampelozizyphus amazonicus Ducke, a plant that is widely used by the population of the Amazonian region to prevent and treat malaria, was investigated in this work, which describes, for the first time, the antiplasmodial activity of its extracts and associates this activity with its isolated constituents. Methods: Different extracts with solvents of increasing polarity (hexane, chloroform, ethanol, and water) were obtained of the root bark. This procedure resulted in extracts that were characterized for their constituents. The cytotoxicity and activity of the extracts against Plasmodium berghei (schizontocidal activity, liver stage) and Plasmodium falciparum (3D7 and Dd2 strains, erythrocyte stage) were assessed in vitro. Results: Of the four extracts assayed against P. berghei, the chloroform extract showed the greatest activity, with an inhibitory concentration 50% (IC50) value of 30.1 µg/mL, followed by the aqueous extract (IC50 = 39.9 µg/mL). The chloroform extract exhibited the highest antiplasmodial activity in the erythrocyte stage of P. falciparum, with an IC50 value lower than 15 µg/mL. Fractionation of this more active extract led to the isolation and elucidation of pentacyclic triterpenes, lupeol, betulin and betulinic acid, which showed antiplasmodial activities with IC50 values ranging from 5.6 to 80.30 µM. The most active of these, betulinic acid, was further quantified in the extracts by high-performance liquid chromatography-photodiode array detector analyzes. The higher amount was found in the chloroform extract, which was the most active one against P. falciparum. Conclusion: The results obtained in this work may partly explain the popular intake of A. amazonicusas an antimalarial remedy in the Amazon region. PMID:26664012

  19. Pseudocyanides of sanguinarine and chelerythrine and their series of structurally simple analogues as new anticancer lead compounds: Cytotoxic activity, structure-activity relationship and apoptosis induction.

    PubMed

    Cao, Fang-Jun; Yang, Rui; Lv, Chao; Ma, Qun; Lei, Ming; Geng, Hui-Ling; Zhou, Le

    2015-01-25

    6-Cyano dihydrosanguinarine (CNS) and 6-cyano dihydrochelerythrine (CNC) are respectively artificial derivatives of sanguinarine and chelerythrine, two anticancer quaternary benzo[c]phenanthridine alkaloids (QBAs) while 1-cyano-2-aryl-1,2,3,4-tetrahydroisoquinolines (CATHIQs) are a class of structurally simple analogues of CNS or CNC. This study investigated the inhibition activity of CNS, CNC and CATHIQs on cancer cells, apoptosis induction as well as their preliminary SAR. The results showed that CNS and 18 out of CATHIQs showed IC50 values of 0.53 and 0.62-2.24μM against NB4 and 1.53 and 2.99-11.17μM against MKN-45 cells, respectively, superior to a standard anticancer drug cis-platinum with IC50 of 2.39 and 11.36μM. CNC showed a higher activity against NB4 cells (IC50=1.85μM) and a moderate activity against MKN-45 cells (IC50=12.72μM). Among all CATHIQs, 2 and 17 gave the highest activity against NB4 cells and MKN-45 cells (IC50=0.62 and 2.99μM), respectively. DAPI staining, AO/EB staining and ultrastructure analysis of cells demonstrated that CATHIQs were able to induce apoptosis of the cells in a concentration-dependent manner. SAR showed that substitution patterns on the N-aromatic ring significantly influenced the activity of CATHIQs. The general trend was that the introduction of electron-withdrawing substituents like halogen atom, nitro, trifluoromethyl led to a significant improvement of the activity, while the presence of electron-donating groups like methyl, methoxyl caused a reduction of the activity. In most cases, the 2' site was the most favorable substitution position for the improvement of the activity. Thus, the present results strongly suggested that QBA-type pseudocyanides may serve as potential alternatives of anticancer QBAs while CATHIQs should be a class of promising lead compounds for the development of new QBA-like-type anticancer drugs. CNS exhibited the highest cytotoxicities with IC50 values of 0.53μM on NB4 cells and 1.53

  20. Highly and Broad-Spectrum In Vitro Antitumor Active cis-Dichloridoplatinum(II) Complexes with 7-Azaindoles

    PubMed Central

    Štarha, Pavel; Dvořák, Zdeněk; Trávníček, Zdeněk

    2015-01-01

    The cis-[PtCl2(naza)2] complexes (1–3) containing monosubstituted 7-azaindole halogeno-derivatives (naza), showed significantly higher activity than cisplatin towards ovarian carcinoma A2780, its cisplatin-resistant variant A2780R, osteosarcoma HOS, breast carcinoma MCF7 and cervix carcinoma HeLa cell lines, with the IC50 values of 3.8, 3.5, 4.5, 2.7, and 9.2 μM, respectively, obtained for the most active complex 3. As for 4 and 5 having disubstituted 7-azaindoles in their molecule, the significant cytotoxicity was detected only for 4 against A2780 (IC50 = 4.8 μM), A2780R (IC50 = 3.8 μM) and HOS (IC50 = 4.3 μM), while 5 was evaluated as having only moderate antiproliferative effect against the mentioned cancer cell lines with IC50 = 33.4, 24.7 and 46.7 μM, respectively. All the studied complexes 1–5 effectively avoided the acquired resistance of ovarian carcinoma cell line. On the other hand, the complexes did not reveal any inhibition activity on the purified 20S proteasome from the A2780 cells. The representative complexes 3 and 5 showed low ability to be hydrolysed, but their stability was markedly lowered in the presence of physiological sulphur-containing biomolecule glutathione (GSH), as proved by the 1H NMR spectroscopy and mass spectrometry studies. A rate of interaction of the studied complexes with GSH was affected by an addition of another mechanistically relevant biomolecule guanosine monophosphate. The differences in interactions of 3 and 5 with GSH correlate well with their different cytotoxicity profiles. PMID:26309251

  1. Highly and Broad-Spectrum In Vitro Antitumor Active cis-Dichloridoplatinum(II) Complexes with 7-Azaindoles.

    PubMed

    Štarha, Pavel; Dvořák, Zdeněk; Trávníček, Zdeněk

    2015-01-01

    The cis-[PtCl2(naza)2] complexes (1-3) containing monosubstituted 7-azaindole halogeno-derivatives (naza), showed significantly higher activity than cisplatin towards ovarian carcinoma A2780, its cisplatin-resistant variant A2780R, osteosarcoma HOS, breast carcinoma MCF7 and cervix carcinoma HeLa cell lines, with the IC50 values of 3.8, 3.5, 4.5, 2.7, and 9.2 μM, respectively, obtained for the most active complex 3. As for 4 and 5 having disubstituted 7-azaindoles in their molecule, the significant cytotoxicity was detected only for 4 against A2780 (IC50 = 4.8 μM), A2780R (IC50 = 3.8 μM) and HOS (IC50 = 4.3 μM), while 5 was evaluated as having only moderate antiproliferative effect against the mentioned cancer cell lines with IC50 = 33.4, 24.7 and 46.7 μM, respectively. All the studied complexes 1-5 effectively avoided the acquired resistance of ovarian carcinoma cell line. On the other hand, the complexes did not reveal any inhibition activity on the purified 20S proteasome from the A2780 cells. The representative complexes 3 and 5 showed low ability to be hydrolysed, but their stability was markedly lowered in the presence of physiological sulphur-containing biomolecule glutathione (GSH), as proved by the 1H NMR spectroscopy and mass spectrometry studies. A rate of interaction of the studied complexes with GSH was affected by an addition of another mechanistically relevant biomolecule guanosine monophosphate. The differences in interactions of 3 and 5 with GSH correlate well with their different cytotoxicity profiles. PMID:26309251

  2. C19-Norditerpenoid Alkaloids from Aconitum szechenyianum and Their Effects on LPS-Activated NO Production.

    PubMed

    Wang, Fei; Yue, Zhenggang; Xie, Pei; Zhang, Li; Li, Zhen; Song, Bei; Tang, Zhishu; Song, Xiaomei

    2016-01-01

    Three new C19-norditerpenoid alkaloids (1-3), along with two known C19-norditerpenoid alkaloids (4-5) have been isolated from Aconitum szechenyianum. Their structures were established by extensive spectroscopic techniques and chemical methods as szechenyianine A (1), szechenyianine B (2), szechenyianine C (3), N-deethyl-3-acetylaconitine (4), and N-deethyldeoxyaconitine (5). Additionally, compounds 1-5 were tested for the inhibition of NO production on LPS-activated RAW264.7 cells with IC50 values of 36.62 ± 6.86, 3.30 ± 0.11, 7.46 ± 0.89, 8.09 ± 1.31, and 11.73 ± 1.94 μM, respectively, while the positive control drug dexamethasone showed inhibitory activity with IC50 value of 8.32 ± 1.45 μM. The structure-activity relationship of aconitine alkaloids were discussed. PMID:27598121

  3. Inhibition of gastric H+, K(+)-ATPase activity by compounds from medicinal plants.

    PubMed

    Freitas, Cristina Setim; Baggio, Cristiane Hatsuko; Mayer, Bárbara; dos Santos, Ana Cristina; Twardowschy, André; Santos, Cid Aimbiré de Moraes; Marques, Maria Consuelo Andrade

    2011-09-01

    H+, K(+)-ATPase enzyme is a therapeutic target for the treatment of gastric disturbances. Several medicinal plants and isolated compounds inhibit the acid gastric secretion through interaction with the proton pump. In order to add new properties to some natural constituents, five compounds, a benzylated derivative of vincoside, a diterpene (abietic acid) and three alkaloids (cephaeline, vinblastine and vindoline), were tested for their activities on gastric H+, K(+)-ATPase isolated from rabbit stomach. All the compounds inhibited H+, K(+)-ATPase activity with varied potency. The IC50 value for benzylvincoside was 121 (50-293) microM, and for abietic acid 177 (148-211) microM. The alkaloids cephaeline, vinblastine and vindoline inhibited the H+, K(+)-ATPase activity with IC50 values of 194, 761 and 846 microM, respectively. The results suggest that benzylvincoside, abietic acid and cephaeline can be important sources for the development of anti-secretor agents. PMID:21941891

  4. Quince (Cydonia oblonga Miller) fruit (pulp, peel, and seed) and Jam: antioxidant activity.

    PubMed

    Silva, Branca M; Andrade, Paula B; Valentão, Patrícia; Ferreres, Federico; Seabra, Rosa M; Ferreira, Margarida A

    2004-07-28

    To study the antioxidant activity of quince fruit (pulp, peel, and seed) and jam, methanolic extracts were prepared. Each extract was fractionated into a phenolic fraction and an organic acid fraction and was analyzed by high-performance liquid chromatography (HPLC)/diode array detection and HPLC/UV, respectively. Antiradical activities of the extracts and fractions were evaluated by a microassay using 1,1'-diphenyl-2-picrylhydrazyl. The phenolic fraction always exhibited a stronger antioxidant activity than the whole methanolic extract. Organic acid extracts were always the weakest in terms of antiradical activity, which seems to indicate that the phenolic fraction gives a higher contribution for the antioxidant potential of quince fruit and jam. The evaluation of the antioxidant activity of methanolic extracts showed that peel extract was the one presenting the highest antioxidant capacity. The IC50 values of quince pulp, peel, and jam extracts were correlated with the caffeoylquinic acids total content. Among the phenolic fractions, the seed extract was the one that exhibited the strongest antioxidant activity. The IC50 values of quince pulp, peel, and jam phenolic extracts were strongly correlated with caffeoylquinic acids and phenolics total contents. For organic acid fractions, the peel extract was the one that had the strongest antiradical activity. The IC50 values of quince pulp, peel, and jam organic acid fractions were correlated with the ascorbic acid and citric acid contents. PMID:15264903

  5. New sesquiterpene lactones, vernonilides A and B, from the seeds of Vernonia anthelmintica in Uyghur and their antiproliferative activities.

    PubMed

    Ito, Takuya; Aimaiti, Simayijiang; Win, Nwet Nwet; Kodama, Takeshi; Morita, Hiroyuki

    2016-08-01

    A new guaianolide sesquiterpene lactone, vernonilide A (1), and a new elemanolide sesquiterpene lactone, vernonilide B (2), were isolated from the seeds of Vernonia anthelmintica, together with three known elemanolide sesquiterpene lactones (3-5). The structures of the isolated compounds were elucidated on the basis of physicochemical evidences. Compounds 1, 3, and 4 showed strong antiproliferative activities against three human cancer cell lines (A549, HeLa, and MDA-MB-231), with IC50 values ranging from 0.10 to 1.00μM. In addition, 5 exhibited significant antiproliferative activities against HeLa and MDA-MB-231 cells, with IC50 values ranging from 1.90 to 2.20μM. The antiproliferative activities of the acetyl derivatives 6 and 7 prepared from 4 and 3, respectively, against the three cell lines were 4-10-fold weaker than the original activities. PMID:27311895

  6. Cholinesterase inhibitory activity versus aromatic core multiplicity: a facile green synthesis and molecular docking study of novel piperidone embedded thiazolopyrimidines.

    PubMed

    Basiri, Alireza; Murugaiyah, Vikneswaran; Osman, Hasnah; Kumar, Raju Suresh; Kia, Yalda; Hooda, Alysha; Parsons, Richard B

    2014-01-15

    Novel thiazolopyrimidine derivatives have been synthesized via microwave assisted, domino cascade methodology in ionic liquid and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities. Among the newly synthesized compounds 6d, 6a, 6e and 6b displayed higher AChE inhibitory activity than standard drug, galanthamine, with IC50 values of 0.53, 1.47, 1.62 and 2.05μM, respectively. Interestingly, all the compounds except for 6m-r and 6x displayed higher BChE inhibitory potentials than galanthamine with IC50 values ranging from 1.09 to 18.56μM. Molecular docking simulations for 6d possessing the most potent AChE and BChE inhibitory activities, disclosed its binding interactions at the active site gorge of AChE and BChE enzymes. PMID:24369842

  7. Urease Inhibitory Activities of some Commonly Consumed Herbal Medicines

    PubMed Central

    Mahernia, Shabnam; Bagherzadeh, Kowsar; Mojab, Faraz; Amanlou, Massoud

    2015-01-01

    Urease enzyme has a crucial role in the persistent habitation of Helicobacter pylori (H. pylori) that induces gastrointestinal diseases, in particular gastritis, duodenal, peptic ulcer, and gastric cancer. Plants have long been utilized as the biggest source of substances with medicinal properties from natural origin and therefore result in less toxicity and adverse side effects upon usage. 15 medicinal plant extracts were examined against Jack bean urease activity by Berthelot reaction. Each herb was extracted using 80% aqueous methanol. The more effective extracts were further tested and their IC50 values were determined. Three plant extracts including Ginkgo biloba, Rhus coriaria, and Matricaria inodora were found to be the most effective ones with IC50 values of 36.17, 80.29, and 100.6 μg/mL, respectively. PMID:26330884

  8. In Vitro Screening for Anti-Cholinesterase and Antioxidant Activity of Methanolic Extracts of Ayurvedic Medicinal Plants Used for Cognitive Disorders

    PubMed Central

    Mathew, Maya; Subramanian, Sarada

    2014-01-01

    Inhibition of Acetylcholinesterase (AChE) is still considered as the main therapeutic strategy against Alzheimer’s disease (AD). Many plant derived phytochemicals have shown AChE inhibitory activity in addition to the currently approved drugs for AD. In the present study, methanolic extracts of 20 plants used in Indian Ayurvedic system of medicine for improving cognitive function were screened for acetylcholinesterase inhibitory activity by Ellman’s microplate colorimetric method. Out of 20 extracts, Emblica officinalis, Nardostachys jatamansi, Nelumbo nucifera, Punica granatum and Raulfia Serpentina showed IC50 values <100 µg/ml for acetylcholinesterase inhibitory activity. Antioxidant activities of these plants were assessed by DPPH scavenging assay. Among the extracts used, antioxidant activity was highest for Terminalia chebula and Emblica officinalis with IC50 values <10 µg/ml. Considering the complex multifactorial etiology of AD, these plant extracts will be safer and better candidates for the future disease modifying therapies against this devastating disease. PMID:24466247

  9. Design, synthesis and evaluation of rivastigmine and curcumin hybrids as site-activated multitarget-directed ligands for Alzheimer's disease therapy.

    PubMed

    Li, Yujie; Peng, Peng; Tang, Li; Hu, Yunzhen; Hu, Yongzhou; Sheng, Rong

    2014-09-01

    A series of novel 2-methoxy-phenyl dimethyl-carbamate derivatives were designed, synthesized and evaluated as site-activated MTDLs based on rivastigmine and curcumin. Most of them exhibited good to excellent AChE and BuChE inhibitory activities with sub-micromolar IC50 values. Among all the compounds, 6a demonstrated the most potent AChE inhibition with IC50 value of 0.097μM, which is about 20-fold than that of rivastigmine. In addition, the three selected compounds 5a, 6a and 6e demonstrated inhibitory activity against Aβ self-aggregation similar to cucurmin in TEM assay, which is obviously different from the weak activity of rivastigmine. Moreover, the hydrolysate of 6a (compound 7) also showed potent ABTS(+) scavenging and moderate copper ion chelating activity in vitro. PMID:25082512

  10. Synthesis, characterization, and antioxidant/cytotoxic activity of new chromone Schiff base nano-complexes of Zn(II), Cu(II), Ni(II) and Co(II)

    NASA Astrophysics Data System (ADS)

    Saif, M.; El-Shafiy, Hoda F.; Mashaly, Mahmoud M.; Eid, Mohamed F.; Nabeel, A. I.; Fouad, R.

    2016-08-01

    A chromone Schiff base complexes of Zn(II) (1), Cu(II) (2), Ni(II) (3) and Co(II) (4) were successfully prepared in nano domain with crystalline or amorphous structures. The spectroscopic data revealed that the Schiff base ligand behaves as a monoanionic tridentate ligand. The metal complexes exhibited octahedral geometry. Transmission electron microscope (TEM) analysis showed that Cu(II) complex have aggregated nanospheres morphology. The obtained nano-complexes were tested as antioxidant and antitumor agents. The H2L and its Cu(II) complex (2) were found to be more potent antioxidant (IC50(H2L) = 0.93 μM; IC50(Cu(II) complex) = 1.1 μM than standard ascorbic acid (IC50 = 2.1 μM) as evaluated by DPPH• method. The H2L and its complexes (1-4) were tested for their in vitro cytotoxicity against Ehrlich Ascites Carcinoma cell line (EAC). The Cu(II) nano-complex (2) effectively inhibited EAC growth with IC50 value of 47 μM in comparison with its parent compound and other prepared complexes. The high antioxidant activity and antitumor activity of Cu(II) nano-complex (2) were attributed to their chemical structure, Cu(II) reducing capacity, and nanosize property. The toxicity test on mice showed that Zn(II) (1) and Cu(II) (2) nano-complex have lower toxicity than the standard cis-platin.

  11. Cytotoxic activity screening of Bangladeshi medicinal plant extracts.

    PubMed

    Akter, Raushanara; Uddin, Shaikh J; Grice, I Darren; Tiralongo, Evelin

    2014-01-01

    The cytotoxic activity of 23 crude methanol extracts from 19 Bangladeshi medicinal plants was investigated against healthy mouse fibroblasts (NIH3T3), healthy monkey kidney (VERO) and four human cancer cell lines (gastric, AGS; colon, HT-29; and breast, MCF-7 and MDA-MB-231) using MTT assay. High cytotoxicity across all cell lines tested was exhibited by Aegiceras corniculatum (fruit) and Hymenodictyon excelsum (bark) extracts (IC50 values ranging from 0.0005 to 0.9980 and 0.08 to 0.44 mg/mL, respectively). Fourteen extracts from 11 plant species, namely Clitoria ternatea (flower and leaf), Dillenia indica (leaf), Diospyros peregrina (leaf), Dipterocarpus turbinatus (bark and leaf), Ecbolium viride (leaf), Glinus oppositifolius (whole plant), Gnaphalium luteoalbum (leaf), Jasminum sambac (leaf), Lannea coromandelica (bark and leaf), Mussaenda glabrata (leaf) and Saraca asoca (leaf), were also significantly cytotoxic (IC50 < 1.0 mg/mL) against at least one of the cancer cell lines tested. More selectively, Avicennia alba (leaf), C. ternatea (flower and leaf), Caesalpinia pulcherrima (leaf), E. viride (leaf) and G. oppositifolius (whole plant) showed cytotoxicity only against both of the breast cancer cell lines (MCF-7 and MDA-MB-231). In contrast, C. ternatea (flower and leaf) exhibited high cytotoxic activity against MDA-MB-231 (IC50 values of 0.11 and 0.49 mg/mL, respectively), whereas E. viride and G. oppositifolius whole plant extracts exhibited high activity against MCF-7 cells (IC50 values of 0.06 and 0.15 mg/mL, respectively). The cytotoxic activity test results for 9 of the plant species correlate with their traditional use as anticancer agents, thus making them interesting sources for further drug development. PMID:23846168

  12. Antioxidant and free radical scavenging activity of Spondias pinnata

    PubMed Central

    Hazra, Bibhabasu; Biswas, Santanu; Mandal, Nripendranath

    2008-01-01

    Background Many diseases are associated with oxidative stress caused by free radicals. Current research is directed towards finding naturally-occurring antioxidants of plant origin. The aim of the present study was to evaluate the in vitro antioxidant activities of Spondias pinnata stem bark extract. Methods A 70% methanol extract of Spondias pinnata stem bark was studied in vitro for total antioxidant activity, for scavenging of hydroxyl radicals, superoxide anions, nitric oxide, hydrogen peroxide, peroxynitrite, singlet oxygen and hypochlorous acid, and for iron chelating capacity, reducing power, and phenolic and flavonoid contents. Results The extract showed total antioxidant activity with a trolox equivalent antioxidant concentration (TEAC) value of 0.78 ± 0.02. The IC50 values for scavenging of free radicals were 112.18 ± 3.27 μg/ml, 13.46 ± 0.66 μg/ml and 24.48 ± 2.31 μg/ml for hydroxyl, superoxide and nitric oxide, respectively. The IC50 for hydrogen peroxide scavenging was 44.74 ± 25.61 mg/ml. For the peroxynitrite, singlet oxygen and hypochlorous acid scavenging activities the IC50 values were 716.32 ± 32.25 μg/ml, 58.07 ± 5.36 μg/ml and 127.99 ± 6.26 μg/ml, respectively. The extract was found to be a potent iron chelator with IC50 = 66.54 ± 0.84 μg/ml. The reducing power was increased with increasing amounts of extract. The plant extract (100 mg) yielded 91.47 ± 0.004 mg/ml gallic acid-equivalent phenolic content and 350.5 ± 0.004 mg/ml quercetin-equivalent flavonoid content. Conclusion The present study provides evidence that a 70% methanol extract of Spondias pinnata stem bark is a potential source of natural antioxidants. PMID:19068130

  13. Biological Activities of the Essential Oil from Erigeron floribundus.

    PubMed

    Petrelli, Riccardo; Orsomando, Giuseppe; Sorci, Leonardo; Maggi, Filippo; Ranjbarian, Farahnaz; Biapa Nya, Prosper C; Petrelli, Dezemona; Vitali, Luca A; Lupidi, Giulio; Quassinti, Luana; Bramucci, Massimo; Hofer, Anders; Cappellacci, Loredana

    2016-01-01

    Erigeron floribundus (Asteraceae) is an herbaceous plant widely used in Cameroonian traditional medicine to treat various diseases of microbial and non-microbial origin. In the present study, we evaluated the in vitro biological activities displayed by the essential oil obtained from the aerial parts of E. floribundus, namely the antioxidant, antimicrobial and antiproliferative activities. Moreover, we investigated the inhibitory effects of E. floribundus essential oil on nicotinate mononucleotide adenylyltransferase (NadD), a promising new target for developing novel antibiotics, and Trypanosoma brucei, the protozoan parasite responsible for Human African trypanosomiasis. The essential oil composition was dominated by spathulenol (12.2%), caryophyllene oxide (12.4%) and limonene (8.8%). The E. floribundus oil showed a good activity against Staphylococcus aureus (inhibition zone diameter, IZD of 14 mm, minimum inhibitory concentration, MIC of 512 µg/mL). Interestingly, it inhibited the NadD enzyme from S. aureus (IC50 of 98 µg/mL), with no effects on mammalian orthologue enzymes. In addition, T. brucei proliferation was inhibited with IC50 values of 33.5 µg/mL with the essential oil and 5.6 µg/mL with the active component limonene. The essential oil exhibited strong cytotoxicity on HCT 116 colon carcinoma cells with an IC50 value of 14.89 µg/mL, and remarkable ferric reducing antioxidant power (tocopherol-equivalent antioxidant capacity, TEAC = 411.9 μmol·TE/g). PMID:27529211

  14. Design, Synthesis, and Antiplasmodial Activity of Hybrid Compounds Based on (2R,3S)-N-Benzoyl-3-phenylisoserine

    PubMed Central

    2013-01-01

    A series of hybrid compounds based on (2R,3S)-N-benzoyl-3-phenylisoserine, artemisinin, and quinoline moieties was synthesized and tested for in vitro antiplasmodial activity against erythrocytic stages of K1 and W2 strains of Plasmodium falciparum. Two hybrid compounds incorporating (2R,3S)-N-benzoyl-3-phenylisoserine and artemisinin scaffolds were 3- to 4-fold more active than dihydroartemisinin, with nanomolar IC50 values against Plasmodium falciparum K1 strain. PMID:24900723

  15. Anti-Plasmodium falciparum activity of quinoline-sulfonamide hybrids.

    PubMed

    Pinheiro, Luiz C S; Boechat, Núbia; Ferreira, Maria de Lourdes G; Júnior, Carlos C S; Jesus, Antônio M L; Leite, Milene M M; Souza, Nicolli B; Krettli, Antoniana U

    2015-09-01

    Fifteen quinoline-sulfonamide hybrids, with a 7-chloroquinoline moiety connected by a linker group to arylsulfonamide moieties with different substituents in the 4-position were synthesized and assayed against Plasmodium falciparum. The compounds displayed high schizonticidal blood activity in vitro, with IC50 values ranging from 0.05 to 1.63 μM, in the anti-HPR2 assay against clone W2-chloroquine-resistant; ten of them showed an IC50 (ranging from 0.05 to 0.40 μM) lower than that of chloroquine and sulfadoxine. Among them, two compounds inhibited Plasmodium berghei parasitemia by 47% and 49% on day 5 after mice inoculation. The most active, in vivo, hybrid 13 is considered to be a new prototype for the development of an antimalarial drug against chloroquine-resistant parasites. PMID:26190461

  16. Antileishmanial Activity of Compounds Isolated from Sassafras albidum.

    PubMed

    Pulivarthi, Divya; Steinberg, Kelly Marie; Monzote, Lianet; Piñón, Abel; Setzer, William N

    2015-07-01

    Leishmaniasis is a neglected tropical disease caused by Leishmania parasitic protozoa, which currently lacks efficient treatment. Natural products have shown promise as a potential source for antiprotozoal drugs. This work focuses on the antileishmanial potential of Sassafras albidum (Lauraceae) bark extract. The crude bark extract of S. albidum showed excellent antileishmanial activity with an IC50 value less than 12.5 μg/mL against promastigotes of L. amazonensis. The chloroform stem bark extract of S. albidum was subjected to preparative column chromatography. Five compounds were isolated, purified by recrystallization, and identified as sesamin, spinescin, β-sitosterol, hexatriacontanal, and 1-triacontanol. Antileishmanial and cytotoxic screening were performed on these compounds. Sesamin exhibited the best activity against L. amazonensis with an IC50 of 15.8 μg/mL and was not cytotoxic to mouse macrophage cells (CC50 > 100 μg/mL). PMID:26411017

  17. Three new alkaloids from Veratrum grandiflorum Loes with inhibition activities on Hedgehog pathway.

    PubMed

    Gao, Lijuan; Chen, Fengyang; Li, Xiaoyu; Xu, Shifang; Huang, Wenhai; Ye, Yiping

    2016-10-01

    Three new steroidal alkaloids 1-3, together with four known compounds 4-7, were isolated from the ethanol extract of Veratrum grandiflorum Loes. Their structures were elucidated by NMR (1D and 2D NMR) and MS spectroscopic data. The inhibition activities on Hedgehog (Hh) pathway were evaluated using a cell-based bioassay system (Shh-LIGHT 2 cells). The results showed that compounds 1-3 and 5 displayed inhibitory activities obviously with the IC50 values of 0.63-3.11μM. Among them, compound 5 showed the most prominent inhibition activity (IC50=0.63±0.02μM). Thus, these active alkaloids may be potent natural compounds as Hh pathway inhibitors for the treatment of various cancers. PMID:27567371

  18. Asteltoxins with Antiviral Activities from the Marine Sponge-Derived Fungus Aspergillus sp. SCSIO XWS02F40.

    PubMed

    Tian, Yong-Qi; Lin, Xiu-Ping; Wang, Zhen; Zhou, Xue-Feng; Qin, Xiao-Chu; Kaliyaperumal, Kumaravel; Zhang, Tian-Yu; Tu, Zheng-Chao; Liu, Yonghong

    2015-01-01

    Two new asteltoxins named asteltoxin E (2) and F (3), and a new chromone (4), together with four known compounds were isolated from a marine sponge-derived fungus, Aspergillus sp. SCSIO XWS02F40. The structures of the compounds (1-7) were determined by the extensive 1D- and 2D-NMR spectra, and HRESIMS spectrometry. All the compounds were tested for their antiviral (H1N1 and H3N2) activity. Compounds 2 and 3 showed significant activity against H3N2 with the prominent IC50 values of 6.2 ± 0.08 and 8.9 ± 0.3 μM, respectively. In addition, compound 2 also exhibited inhibitory activity against H1N1 with an IC50 value of 3.5 ± 1.3 μM. PMID:26712735

  19. Screening Active Compounds from Garcinia Species Native to China Reveals Novel Compounds Targeting the STAT/JAK Signaling Pathway.

    PubMed

    Xu, Linfeng; Lao, Yuanzhi; Zhao, Yanhui; Qin, Jian; Fu, Wenwei; Zhang, Yingjia; Xu, Hongxi

    2015-01-01

    Natural compounds from medicinal plants are important resources for drug development. In a panel of human tumor cells, we screened a library of the natural products from Garcinia species which have anticancer potential to identify new potential therapeutic leads and discovered that caged xanthones were highly effective at suppressing multiple cancer cell lines. Their anticancer activities mainly depended on apoptosis pathways. For compounds in sensitive cancer line, their mechanisms of mode of action were evaluated. 33-Hydroxyepigambogic acid and 35-hydroxyepigambogic acid exhibited about 1 μM IC50 values against JAK2/JAK3 kinases and less than 1 μM IC50 values against NCI-H1650 cell which autocrined IL-6. Thus these two compounds provided a new antitumor molecular scaffold. Our report describes 33-hydroxyepigambogic acid and 35-hydroxyepigambogic acid that inhibited NCI-H1650 cell growth by suppressing constitutive STAT3 activation via direct inhibition of JAK kinase activity. PMID:26090459

  20. Screening Active Compounds from Garcinia Species Native to China Reveals Novel Compounds Targeting the STAT/JAK Signaling Pathway

    PubMed Central

    Xu, Linfeng; Lao, Yuanzhi; Zhao, Yanhui; Qin, Jian; Fu, Wenwei; Zhang, Yingjia; Xu, Hongxi

    2015-01-01

    Natural compounds from medicinal plants are important resources for drug development. In a panel of human tumor cells, we screened a library of the natural products from Garcinia species which have anticancer potential to identify new potential therapeutic leads and discovered that caged xanthones were highly effective at suppressing multiple cancer cell lines. Their anticancer activities mainly depended on apoptosis pathways. For compounds in sensitive cancer line, their mechanisms of mode of action were evaluated. 33-Hydroxyepigambogic acid and 35-hydroxyepigambogic acid exhibited about 1 μM IC50 values against JAK2/JAK3 kinases and less than 1 μM IC50 values against NCI-H1650 cell which autocrined IL-6. Thus these two compounds provided a new antitumor molecular scaffold. Our report describes 33-hydroxyepigambogic acid and 35-hydroxyepigambogic acid that inhibited NCI-H1650 cell growth by suppressing constitutive STAT3 activation via direct inhibition of JAK kinase activity. PMID:26090459

  1. Flavonoid glycosides from Chromolaena odorata leaves and their in vitro cytotoxic activity.

    PubMed

    Hung, Tran Manh; Cuong, To Dao; Dang, Nguyen Hai; Zhu, Shu; Long, Pham Quoc; Komatsu, Katsuko; Min, Byung Sun

    2011-01-01

    Two new flavonoid glycosides, (1, 2), and eleven known compounds, (3-13), were isolated from from a 70% EtOH extract of the leaves of Chromolaena odorata (Asteraceae). Their structures were elucidated by 1D and 2D NMR spectroscopic interpretation as well as by chemical studies. The newly isolated compounds were tested in vitro for their cytotoxic activities against the LLC and HL-60 cancer cell lines. Compound 1 showed cytotoxicity against LLC and HL-60 cancer cell lines with IC(50) values of 28.2 and 11.6 µM, respectively. Compound 2 exhibited significant cytotoxic activity in the inhibition of HL-60 cancer cell lines with IC(50) value of 10.8 µM. PMID:21212562

  2. Screening of Korean Medicinal Plant Extracts for α-Glucosidase Inhibitory Activities

    PubMed Central

    Sancheti, Shruti; Sancheti, Sandesh; Lee, Seung-Hun; Lee, Jae-Eun; Seo, Sung-Yum

    2011-01-01

    Glycosidases are the enzymes involved in various biochemical processes related to metabolic disorders and diseases. Therefore, much effort has been focused on searching novel pharmacotherapy for the treatment of these ailments from medicinal plants due to higher safety margins. To pursue these efforts, the present study was performed to evaluate the α-glucosidase inhibitory activities of thirty Korean medicinal plant extracts. Among the plants studied, Euonymus sachalinensis, Rhododendron schlippenbachii, Astilbe chinensis and Juglans regia showed the strongest α-glucosidase inhibitory activity with IC50 values of 10, 20, 30 and 80 µg/mL, respectively. In addition, Meliosma oldhamii and Symplocos chinensis showed moderate α-glucosidase inhibition with IC50 values of 150 and 220 µg/mL, respectively. Therefore, they might prove to be a potential natural source for the treatment of metabolic ailments such as, diabetes, and need further investigations. PMID:24250352

  3. Netamines H-N, tricyclic alkaloids from the marine sponge Biemna laboutei and their antimalarial activity.

    PubMed

    Gros, Emmanuelle; Al-Mourabit, Ali; Martin, Marie-Thérèse; Sorres, Jonathan; Vacelet, Jean; Frederich, Michel; Aknin, Maurice; Kashman, Yoel; Gauvin-Bialecki, Anne

    2014-04-25

    Chemical examination of the CH2Cl2-MeOH (1:1) extract of the Madagascar sponge Biemna laboutei resulted in the isolation of seven new tricyclic alkaloids, netamines H-N (1-7), along with the known netamine G and mirabilins A, C, and F. Their structures were elucidated by interpretation of 1D and 2D NMR spectra and HRESIMS data. All compounds were evaluated for their cytotoxicity against KB cells and their antiplasmodial activity. Netamine M (6) was found to be cytotoxic, with an IC50 value in the micromolar range, and netamine K (4) exhibited activity against Plasmodium falciparum with an IC50 value of 2.4 μM. PMID:24601655

  4. Anti-herpes simplex virus activity of alkaloids isolated from Stephania cepharantha.

    PubMed

    Nawawi, A; Ma, C; Nakamura, N; Hattori, M; Kurokawa, M; Shiraki, K; Kashiwaba, N; Ono, M

    1999-03-01

    By screening water and MeOH extracts of 30 Chinese medicinal plants for their anti-herpes simplex virus (HSV)-1 activity, a MeOH extract of the root tubers of Stephania cepharantha HAYATA showed the most potent activity on the plaque reduction assay with an IC50 value of 18.0 microg/ml. Of 49 alkaloids isolated from the MeOH extract, 17 alkaloids were found to be active against HSV-1, including 13 bisbenzylisoquinoline, 1 protoberberine, 2 morphinane and 1 proaporphine alkaloids, while benzylisoquinoline and hasubanane alkaloids were inactive. Although N-methylcrotsparine was active against HSV-1, as well as HSV-1 thymidine kinase deficient (acyclovir resistant type, HSV-1 TK-) and HSV-2 (IC50 values of 8.3, 7.7 and 6.7 microg/ml, respectively), it was cytotoxic. FK-3000 was found to be the most active against HSV-1, HSV-1 TK- and HSV-2 (IC50 values of 7.8, 9.9 and 8.7 microg/ml) with in vitro therapeutic indices of 90, 71 and 81, respectively. FK-3000 was found to be a promising candidate as an anti-HSV agent against HSV-1, acyclovir (ACV) resistant-type HSV-1 and HSV-2. PMID:10220283

  5. Substitution of the phosphonic acid and hydroxamic acid functionalities of the DXR inhibitor FR900098: an attempt to improve the activity against Mycobacterium tuberculosis.

    PubMed

    Andaloussi, Mounir; Lindh, Martin; Björkelid, Christofer; Suresh, Surisetti; Wieckowska, Anna; Iyer, Harini; Karlén, Anders; Larhed, Mats

    2011-09-15

    Two series of FR900098/fosmidomycin analogs were synthesized and evaluated for MtDXR inhibition and Mycobacterium tuberculosis whole-cell activity. The design rationale of these compounds involved the exchange of either the phosphonic acid or the hydroxamic acid part for alternative acidic and metal-coordinating functionalities. The best inhibitors provided IC(50) values in the micromolar range, with a best value of 41 μM. PMID:21824775

  6. Antiproliferative Activity of Xanthones Isolated from Artocarpus obtusus

    PubMed Central

    Hashim, Najihah Mohd; Rahmani, Mawardi; Ee, Gwendoline Cheng Lian; Sukari, Mohd Aspollah; Yahayu, Maizatulakmal; Oktima, Winda; Ali, Abd Manaf; Go, Rusea

    2012-01-01

    An investigation of the chemical constituents in Artocarpus obtusus species led to the isolation of three new xanthones, pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2), and pyranocycloartobiloxanthone B (3). The compounds were subjected to antiproliferative assay against human promyelocytic leukemia (HL60), human chronic myeloid leukemia (K562), and human estrogen receptor (ER+) positive breast cancer (MCF7) cell lines. Pyranocycloartobiloxanthone A (1) consistently showed strong cytotoxic activity against the three cell lines compared to the other two with IC50 values of 0.5, 2.0 and 5.0 μg/mL, respectively. Compound (1) was also observed to exert antiproliferative activity and apoptotic promoter towards HL60 and MCF7 cell lines at respective IC50 values. The compound (1) was not toxic towards normal cell lines human nontumorigenic breast cell line (MCF10A) and human peripheral blood mononuclear cells (PBMCs) with IC50 values of more than 30 μg/mL. PMID:21960741

  7. Potential amoebicidal activity of hydrazone derivatives: synthesis, characterization, electrochemical behavior, theoretical study and evaluation of the biological activity.

    PubMed

    Toledano-Magaña, Yanis; García-Ramos, Juan Carlos; Navarro-Olivarria, Marisol; Flores-Alamo, Marcos; Manzanera-Estrada, Mayra; Ortiz-Frade, Luis; Galindo-Murillo, Rodrigo; Ruiz-Azuara, Lena; Meléndrez-Luevano, Ruth Ma; Cabrera-Vivas, Blanca M

    2015-01-01

    Four new hydrazones were synthesized by the condensation of the selected hydrazine and the appropriate nitrobenzaldehyde. A complete characterization was done employing 1H- and 13C-NMR, electrochemical techniques and theoretical studies. After the characterization and electrochemical analysis of each compound, amoebicidal activity was tested in vitro against the HM1:IMSS strain of Entamoeba histolytica. The results showed the influence of the nitrobenzene group and the hydrazone linkage on the amoebicidal activity. meta-Nitro substituted compound 2 presents a promising amoebicidal activity with an IC50 = 0.84 μM, which represents a 7-fold increase in cell growth inhibition potency with respect to metronidazole (IC50 = 6.3 μM). Compounds 1, 3, and 4 show decreased amoebicidal activity, with IC50 values of 7, 75 and 23 µM, respectively, as a function of the nitro group position on the aromatic ring. The observed differences in the biological activity could be explained not only by the redox potential of the molecules, but also by their capacity to participate in the formation of intra- and intermolecular hydrogen bonds. Redox potentials as well as the amoebicidal activity can be described with parameters obtained from the DFT analysis. PMID:26035095

  8. Inhibitory and Activating Effects of Some Flavonoid Derivatives on Human Pyruvate Kinase Isoenzyme M2.

    PubMed

    Adem, Sevki; Aslan, Abdulselam; Ahmed, Ishtiaq; Krohn, Karsten; Guler, Caglar; Comaklı, Veysel; Demirdag, Ramazan; Kuzu, Muslum

    2016-02-01

    Pyruvate kinase isoenzyme M2 (PKM2) is expressed excessively in many different cancer types and it plays an important role in the control of glucose metabolism. Thus, it is evaluated as an important target in the development of medication for cancer. The flavonoids comprise a large group of natural products with variable phenolic structures and occur mainly in plants. They are of great interest due to their biological properties. In this study, the effects of various flavonoid derivatives on the PKM2 enzyme activity were analyzed in vitro. The flavonoid derivatives 1 and 2 showed inhibition effect with IC50 values of <60 μM. IC50 values of compounds 3-8 were calculated as 134, 415, 145, 163, 295 μM, and 3.5 mM, respectively. The molecules 9-12 showed an activation effect with values of AC50 of less than 90 μM. The IC50 values of the derivatives 13-17 were calculated as 115, 150, 200, 221, and 275 μM, respectively. The results show that catechin derivatives can be probably used as lead compounds for the design of PKM2 enzyme activators and inhibitors. PMID:26708302

  9. Antiproliferative Activity of β-Hydroxy-β-Arylalkanoic Acids

    PubMed Central

    Dilber, Sanda P.; Žižak, Željko S.; Stanojković, Tatjana P.; Juranić, Zorica D.; Drakulić, Branko J.; Juranić, Ivan O.

    2007-01-01

    Article describes the synthesis of fifteen β-hydroxy-β-arylalkanoic acids by Reformatsky reaction using the 1-ethoxyethyl-2-bromoalkanoates, aromatic or cycloalkyl ketones or aromatic aldehydes. The short survey of previously reported synthetic procedures for title compounds, is given. The majority of obtained compounds exert antiproliferative activity in vitro toward human: HeLa, Fem-X cells, K562, and LS174 cells, having IC50 values from 62.20 to 205 μM. The most active compound is 3-OH-2,2-di-Me-3-(4- biphenylyl)-butanoic acid, having the IC50 value 62.20 μM toward HeLa cells. Seven examined compounds did not affect proliferation of healthy human blood peripheral mononuclear cells (PBMC and PBMC+ PHA), IC50 > 300 μM. The preliminary QSAR results show that estimated lipophilicity of compounds influences their antiproliferative activity in the first place. The ability of dehydration, and the spatial arrangement of hydrophobic portion, HBD and HBA in molecules are has almost equal importance as lipophilicity.

  10. Discovery and Structure–Activity Relationship of Novel 2,3-Dihydrobenzofuran-7-carboxamide and 2,3-Dihydrobenzofuran-3(2H)-one-7-carboxamide Derivatives as Poly(ADP-ribose)polymerase-1 Inhibitors

    PubMed Central

    2015-01-01

    Novel substituted 2,3-dihydrobenzofuran-7-carboxamide (DHBF-7-carboxamide) and 2,3-dihydrobenzofuran-3(2H)-one-7-carboxamide (DHBF-3-one-7-carboxamide) derivatives were synthesized and evaluated as inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1). A structure-based design strategy resulted in lead compound 3 (DHBF-7-carboxamide; IC50 = 9.45 μM). To facilitate synthetically feasible derivatives, an alternative core was designed, DHBF-3-one-7-carboxamide (36, IC50 = 16.2 μM). The electrophilic 2-position of this scaffold was accessible for extended modifications. Substituted benzylidene derivatives at the 2-position were found to be the most potent, with 3′,4′-dihydroxybenzylidene 58 (IC50 = 0.531 μM) showing a 30-fold improvement in potency. Various heterocycles attached at the 4′-hydroxyl/4′-amino of the benzylidene moiety resulted in significant improvement in inhibition of PARP-1 activity (e.g., compounds 66–68, 70, 72, and 73; IC50 values from 0.718 to 0.079 μM). Compound 66 showed selective cytotoxicity in BRCA2-deficient DT40 cells. Crystal structures of three inhibitors (compounds (−)-13c, 59, and 65) bound to a multidomain PARP-1 structure were obtained, providing insights into further development of these inhibitors. PMID:24922587

  11. Coumarins with monoamine oxidase inhibitory activity and antioxidative coumarino-lignans from Hibiscus syriacus.

    PubMed

    Yun, B S; Lee, I K; Ryoo, I J; Yoo, I D

    2001-09-01

    A previously undescribed coumarin and a new coumarino-lignan, together with the known compounds scopoletin and cleomiscosins A, C, and D, have been isolated from the root bark of Hibiscus syriacus, and their structures were assigned on the basis of various spectral studies. The coumarin analogue and scopoletin inhibited monoamine oxidase with moderate IC(50) values. The new coumarino-lignan and cleomiscosin C showed lipid peroxidation inhibitory activity comparable to vitamin E. PMID:11575966

  12. Synthesis and evaluation of antifungal activity of C21-steroidal derivatives.

    PubMed

    Huang, Lie-Jun; Wang, Bin; Zhang, Jian-Xin; Yuan, Chun-Mao; Gu, Wei; Mu, Shu-Zhen; Hao, Xiao-Jiang

    2016-04-15

    The antifungal activities of eleven C21-steroidal compounds isolated from Cynanchum wilfordii, together with thirty-six derivatives of caudatin and qingyangshengenin were evaluated on Sclerotinia sclerotiorum and other five fungal strains by the mycelium growth rate method. Four derivatives 1k, 1y, 10d, and 10j exhibited much stronger inhibitions on growth of S. sclerotiorum with IC50 values of 0.0084, 0.0049, 0.0053, and 0.0034μM, respectively. PMID:26947608

  13. Synthesis, docking and ADMET studies of novel chalcone triazoles for anti-cancer and anti-diabetic activity.

    PubMed

    Chinthala, Yakaiah; Thakur, Sneha; Tirunagari, Shalini; Chinde, Srinivas; Domatti, Anand Kumar; Arigari, Niranjana Kumar; K V N S, Srinivas; Alam, Sarfaraz; Jonnala, Kotesh Kumar; Khan, Feroz; Tiwari, Ashok; Grover, Paramjit

    2015-03-26

    A series of novel chalcone-triazole derivatives were synthesized and screened for in vitro anticancer activity on the human cancer cell lines IMR32 (neuroblastoma), HepG2 (hepatoma) and MCF-7 (breast adenocarcinoma), DU-145 (prostate carcinoma), and A549 (lung adenocarcinoma). Among the tested compounds, 4r showed the most promising anticancer activity in all the cell lines whereas, compounds 4c (IC50 65.86 μM), 4e (IC50 66.28 μM), 4o (IC50 35.81 μM), 4q (IC50 50.82 μM) and 4s (IC50 48.63 μM) showed better activity than the standard doxorubicin (IC50 69.33 μM) in A549 cell line alone. Rat intestinal α-glucosidase inhibitory activity of the synthesized derivatives showed 4m (IC50 67.77 μM), 4p (IC50 74.94 in μM) and 4s (IC50 102.10 μM) as most active compared to others. The in silico docking of synthesized derivatives 4a-4t with DNA topoisomerase IIα revealed the LibDock score in the range of 71.2623-118.29 whereas, compounds 4h, 4m, 4p and 4s with docking target α-glucosidase were in the range of 100.372-107.784. PMID:25743216

  14. Design, synthesis and anti-P. falciparum activity of pyrazolopyridine-sulfonamide derivatives.

    PubMed

    Silva, Thais B; Bernardino, Alice M R; Ferreira, Maria de Lourdes G; Rogerio, Kamilla R; Carvalho, Leonardo J M; Boechat, Nubia; Pinheiro, Luiz C S

    2016-09-15

    Ten 1-phenyl-1H-pyrazolo[3,4-b]pyridine derivatives connected by a linker group to benzenesulfonamide moieties with different substituents in the 4-position were synthesized and assayed against Plasmodium falciparum. These ten compounds exhibited activity in vitro against the chloroquine-resistant clone W2 with IC50 values ranging from 3.46 to 9.30μM. The most active derivatives with substituent R2=Cl or CH3 at the benzenesulfonamide moiety exhibited the lowest IC50. Compounds with an R1=CO2Et substituent at the 5-position of the 1H-pyrazolo[3,4-b]pyridine ring presented lower activity than those with a CN substituent. The 1H-pyrazolo[3,4-b]pyridine system appears to be promising for further studies as an antimalarial for overcoming the burden of resistance in P. falciparum. PMID:27485600

  15. Limonoids from Munronia henryi and their anti-tobacco mosaic virus activity.

    PubMed

    Yan, Ying; Yuan, Chun-Mao; Di, Ying-Tong; Huang, Tao; Fan, Yi-Min; Ma, Yuan; Zhang, Jian-Xin; Hao, Xiao-Jiang

    2015-12-01

    Five new compounds (1-5), including three limonoids, one diterpenoid, and one phytosterol, along with four known limonoids (6-9), were isolated from the ethanolic extracts of whole plants of Munronia henryi. Their structures were elucidated by extensive spectroscopic analysis. In addition, the anti-tobacco mosaic virus (TMV) activities of all the isolated compounds were evaluated by the conventional half-leaf and leaf-disk methods along with Western blot analysis. Most of the tested compounds showed strong antiviral activities, with IC50 values in the range of 14.8-34.0μg/mL, compared with ningnanmycin as a positive control (IC50=44.6μg/mL), and their preliminary structure-activity relationships were also discussed. PMID:26388557

  16. Tacrine-propargylamine derivatives with improved acetylcholinesterase inhibitory activity and lower hepatotoxicity as a potential lead compound for the treatment of Alzheimer's disease.

    PubMed

    Mao, Fei; Li, Jianheng; Wei, Hui; Huang, Ling; Li, Xingshu

    2015-12-01

    A series of tacrine-propargylamine derivatives were synthesised and evaluated as possible anti-Alzheimer's disease (AD) agents. Among these derivatives, compounds 3a and 3b exhibited superior activities and a favourable balance of AChE and BuChE activities (3a: IC50 values of 51.3 and 77.6 nM; 3b: IC50 values of 11.2 and 83.5 nM). Compounds 3a and 3b also exhibited increased hAChE inhibitory activity compared with tacrine by approximately 5- and 28-fold, respectively, and low neurotoxicity. Importantly, these compounds also had lower hepatotoxicity than tacrine. Based on these results, compounds 3a and 3b could be considered as potential lead compounds for the treatment of AD and other AChE related diseases, such as schizophrenia, glaucoma and myasthenia gravis. PMID:25792506

  17. Sesquiterpene Hydroquinones with Protein Tyrosine Phosphatase 1B Inhibitory Activities from a Dysidea sp. Marine Sponge Collected in Okinawa.

    PubMed

    Abdjul, Delfly B; Yamazaki, Hiroyuki; Takahashi, Ohgi; Kirikoshi, Ryota; Ukai, Kazuyo; Namikoshi, Michio

    2016-07-22

    Three new sesquiterpene hydroquinones, avapyran (1), 17-O-acetylavarol (2), and 17-O-acetylneoavarol (3), were isolated from a Dysidea sp. marine sponge collected in Okinawa together with five known congeners: avarol (4), neoavarol (5), 20-O-acetylavarol (6), 20-O-acetylneoavarol (7), and 3'-aminoavarone (8). The structures of 1-3 were assigned on the basis of their spectroscopic data. Compounds 1-3 inhibited the activity of protein tyrosine phosphatase 1B with IC50 values of 11, 9.5, and 6.5 μM, respectively, while known compounds 4-8 gave IC50 values of 12, >32, 10, 8.6, and 18 μM, respectively. In a preliminary investigation on structure-activity relationships, six ester and methoxy derivatives (9-14) were prepared from 4 and 5. PMID:27336796

  18. Antioxidant activity and phenolic content of leaf infusions of Myrtaceae species from Cerrado (Brazilian Savanna).

    PubMed

    Takao, L K; Imatomi, M; Gualtieri, S C J

    2015-11-01

    There is considerable interest in identifying new antioxidants from plant materials. Several studies have emphasized the antioxidant activity of species belonging to the Myrtaceae family. However, there are few reports on these species from the Cerrado (Brazilian savanna). In this study, the antioxidant activity and phenolic content of 12 native Myrtaceae species from the Cerrado were evaluated (Blepharocalyx salicifolius, Eugenia bimarginata, Eugenia dysenterica, Eugenia klotzschiana, Hexachlamys edulis, Myrcia bella, Myrcia lingua, Myrcia splendens, Myrcia tomentosa, Psidium australe, Psidium cinereum, and Psidium laruotteanum). Antioxidant potential was assessed using the antioxidant activity index (AAI) by the DPPH method and total phenolic content (TPC) by the Folin-Ciocalteu assay. There was a high correlation between TPC and AAI values. Psidium laruotteanum showed the highest TPC (576.56 mg GAE/g extract) and was the most potent antioxidant (AAI = 7.97, IC50 = 3.86 µg·mL-1), with activity close to that of pure quercetin (IC50 = 2.99 µg·mL-1). The extracts of nine species showed IC50 of 6.24-8.75 µg·mL-1. Most species showed TPC and AAI values similar to or higher than those for Camellia sinensis, a commonly consumed tea with strong antioxidant properties. The results reveal that the analyzed Myrtaceae species from the Cerrado possess high phenolic contents and antioxidant activities. Thus, they are a potential source of new natural antioxidants. PMID:26675912

  19. In Vitro and In Vivo Anticancer Activity of Root Extracts of Sansevieria liberica Gerome and Labroy (Agavaceae)

    PubMed Central

    Akindele, Abidemi J.; Wani, Zahoor A.; Sharma, Sadhana; Mahajan, Girish; Satti, Naresh K.; Adeyemi, Olufunmilayo O.; Mondhe, Dilip M.; Saxena, Ajit K.

    2015-01-01

    Introduction. Sansevieria liberica Gerome and Labroy (Agavaceae) is a perennial plant widely distributed in tropical Africa. Preparations of the plant are commonly used across Nigeria for the treatment of inflammatory conditions. Based on the fact that herbal medicine is a strong component of integrative medicine, this study was conducted to evaluate the anticancer activity of root extracts of Sansevieria liberica. Methods. Sulforhodamine B (SRB) in vitro cytotoxicity assay, Sarcoma-180 (S-180) ascites and solid tumor, and L1210 lymphoid leukemia in vivo models were used in this study. Results. SL-A002 (IC50 23 µg/mL with HeLa), SL-A003 (IC50 22 µg/mL with HCT-116), and SL-A004 (IC50 23 and 18 µg/mL with A549 and THP-1, resp.) demonstrated significant activity in the SRB cytotoxicity assay. Potency was highest with the following pairs of extract : cancer cell line: SL-A002 : HeLa (IC50 23 µg/mL), SL-A003 : HCT-116 (IC50 22 µg/mL), and SL-A004 : THP-1 (IC50 18 µg/mL). SL-A002 demonstrated significant dose-dependent antitumor activity in the Sarcoma-180 (S-180) ascites model with peak effect produced at the dose of 120 mg/kg (i.p.) with inhibition of 89.36% compared to 97.96% for 5-FU (20 mg/kg i.p.). The inhibition of tumor growth by SL-A002 in the S-180 solid tumor model was 47.40% compared to a value of 50.18% for 5-FU. SL-A002 was also significantly active in the L1210 lymphoid leukemia model with 158.33% increase in mean survival time, the same value for 5-FU. Conclusions. The hydroethanolic extract of Sansevieria liberica, SL-A002, possesses significant anticancer activity to warrant further extensive study to identify, isolate, and characterize the specific bioactive molecules responsible for the observed antitumor activity and the precise mechanism(s) of action. PMID:25810744

  20. A new coumarin and cytotoxic activities of constituents from Cinnamomum cassia.

    PubMed

    Ngoc, Tran Minh; Nhiem, Nguyen Xuan; Khoi, Nguyen Minh; Son, Doan Cao; Hung, Tran Viet; Van Kiem, Phan

    2014-04-01

    A new coumarin derivative, coumacasia (1) and eight known compounds, coumarin (2), cinnamaldehyde (3), 2-methoxycinnamaldehyde (4), 2-hydroxycinnamaldehyde (5), coniferaldehyde (6), cinnamic acid (7), 2-hydroxycinnamic acid (8), and cinnamic alcohol (9), were isolated from the methanol extract of Cinnamomum cassia. Their structures were elucidated by spectral data and by comparison with the reported literature. The cytotoxic activities of compounds 1-9 were evaluated with two human cancer cell lines, HL-60 and A-549. Compound 1 showed growth inhibitory effects in the HL-60 and A-549 cell lines with IC50 values of 8.2 +/- 0.5 and 11.3 +/- 1.1 microM, respectively. Compounds 3-6, and 8 exhibited moderate cytotoxicity with IC50 values ranging from 20.5 to 65.6 microM. PMID:24868863

  1. Large scale screening of commonly used Iranian traditional medicinal plants against urease activity

    PubMed Central

    2012-01-01

    Background and purpose of the study H. pylori infection is an important etiologic impetus usually leading to gastric disease and urease enzyme is the most crucial role is to protect the bacteria in the acidic environment of the stomach. Then urease inhibitors would increase sensitivity of the bacteria in acidic medium. Methods 137 Iranian traditional medicinal plants were examined against Jack bean urease activity by Berthelot reaction. Each herb was extracted using 50% aqueous methanol. The more effective extracts were further tested and their IC50 values were determined. Results 37 plants out of the 137 crude extracts revealed strong urease inhibitory activity (more than 70% inhibition against urease activity at 10 mg/ml concentration). Nine of the whole studied plants crude extracts were found as the most effective with IC50 values less than 500 μg/ml including; Rheum ribes, Sambucus ebulus, Pistachia lentiscus, Myrtus communis, Areca catechu, Citrus aurantifolia, Myristica fragrans, Cinnamomum zeylanicum and Nicotiana tabacum. Conclusions The most potent urease inhibitory was observed for Sambucus ebulus and Rheum ribes extracts with IC50 values of 57 and 92 μg/ml, respectively. PMID:23351780

  2. Inhibition of α-glucosidase activity by ethanolic extract of Melia azedarach L. leaves

    NASA Astrophysics Data System (ADS)

    Sulistiyani; Safithri, Mega; Puspita Sari, Yoana

    2016-01-01

    Development of α-glucosidase inhibitor derived from natural products is an opportunity for a more economic management of diabetes prevention. The objective of this study was to test the activity of α-glucosidase with or without potential inhibitor compounds. By in vitro method, α-glucosidase hydrolizes p-nitrophenyl-α-D-glucopiranoside to glucose and the yellow of p-nitrophenol which can be determined with spectrophotometry at 400 nm. The ability of ethanolic leaf extract of Melia azedarach L. as a-glucosidase inhibitor was compared with that of commercial acarbose (Glucobay®). Acarbose showed strong inhibitory activity against a-glucosidase with IC50 values of 2.154 µg/mL. The crude ethanolic leaf extract of M. azedarach, however, showed less inhibitory activity with IC50 value of 3, 444.114 µg/mL. Total phenolics of M. azedarach leaves EtOH extract showed 17.94 µg GAE/mg extract and flavonoids total compound of 9.55 µg QE/mg extract. Based on the published wide range of IC50 values of extracts reported as a-glucosidase inhibitor which were between 10, 000 ppm-0.66 ppm, our result suggests that extract of M.azedarach leaves is potential candidate for development of anti-hyperglycemic formulation.

  3. Novel "hybrid" iron chelators derived from aroylhydrazones and thiosemicarbazones demonstrate selective antiproliferative activity against tumor cells.

    PubMed

    Lovejoy, David B; Richardson, Des R

    2002-07-15

    We previously demonstrated that 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) and other aroylhydrazone chelators possess potent antineoplastic activity because of their ability to bind iron (Fe). From these studies, we identified structural components of the hydrazones that provide antineoplastic activity, namely the salicylaldehyde and 2-hydroxy-1-naphthylaldehyde moieties. A related group of chelators known as the thiosemicarbazones also show pronounced antitumor activity because of their ability to inhibit ribonucleotide reductase. Considering this, we designed a new series of "hybrid ligands" by condensation of the aldehydes described above with a range of thiosemicarbazides. The parent compound of these ligands is 2-hydroxy-1-naphthylaldehyde thiosemicarbazone (NT). Of 8 NT analogues, 3 chelators, namely NT, N4mT (2-hydroxy-1-naphthylaldehyde-4-methyl-3-thiosemicarbazone), and N44mT (2-hydroxy-1-naphthylaldehyde-4,4-dimethyl-3-thiosemicarbazone), showed high antiproliferative activity against SK-N-MC neuroepithelioma cells (50% inhibitory concentration [IC(50)] = 0.5-1.5 microM). Indeed, their activity was significantly (P <.0001) greater than that of desferrioxamine (DFO) (IC(50) = 22 microM). We demonstrate that 311, a 311 analogue (311m), and several NT-series chelators have significantly (P <.001) greater antiproliferative activity against tumor cells than against a range of normal cell types. For example, the IC(50) values of NT and N4mT in SK-N-MC neuroepithelioma cells were 0.5 microM, whereas for fibroblasts the IC(50) values were greater than 25 microM. Further, the effect of one of the most potent chelators (311m) on preventing the growth of bone marrow stem cell cultures was far less than that of doxorubicin and similar to that of cisplatin. These studies support the further development of these chelators as antiproliferative agents. PMID:12091363

  4. Inhibitory effects of commonly used herbal extracts on UDP-glucuronosyltransferase 1A4, 1A6, and 1A9 enzyme activities.

    PubMed

    Mohamed, Mohamed-Eslam F; Frye, Reginald F

    2011-09-01

    The aim of this study was to investigate the effect of commonly used botanicals on UDP-glucuronosyltransferase (UGT) 1A4, UGT1A6, and UGT1A9 activities in human liver microsomes. The extracts screened were black cohosh, cranberry, echinacea, garlic, ginkgo, ginseng, milk thistle, saw palmetto, and valerian in addition to the green tea catechin epigallocatechin gallate (EGCG). Formation of trifluoperazine glucuronide, serotonin glucuronide, and mycophenolic acid phenolic glucuronide was used as an index reaction for UGT1A4, UGT1A6, and UGT1A9 activities, respectively, in human liver microsomes. Inhibition potency was expressed as the concentration of the inhibitor at 50% activity (IC(50)) and the volume in which the dose could be diluted to generate an IC(50)-equivalent concentration [volume/dose index (VDI)]. Potential inhibitors were EGCG for UGT1A4, milk thistle for both UGT1A6 and UGT1A9, saw palmetto for UGT1A6, and cranberry for UGT1A9. EGCG inhibited UGT1A4 with an IC(50) value of (mean ± S.E.) 33.8 ± 3.1 μg/ml. Milk thistle inhibited both UGT1A6 and UGT1A9 with IC(50) values of 59.5 ± 3.6 and 33.6 ± 3.1 μg/ml, respectively. Saw palmetto and cranberry weakly inhibited UGT1A6 and UGT1A9, respectively, with IC(50) values >100 μg/ml. For each inhibition, VDI was calculated to determine the potential of achieving IC(50)-equivalent concentrations in vivo. VDI values for inhibitors indicate a potential for inhibition of first-pass glucuronidation of UGT1A4, UGT1A6, and UGT1A9 substrates. These results highlight the possibility of herb-drug interactions through modulation of UGT enzyme activities. Further clinical studies are warranted to investigate the in vivo extent of the observed interactions. PMID:21632963

  5. Anti-Influenza Virus Activity and Constituents. Characterization of Paeonia delavayi Extracts.

    PubMed

    Li, Jinhua; Yang, Xianying; Huang, Linfang

    2016-01-01

    Paeonia delavayi, an endemic species in southwestern China, has been widely used as a traditional remedy for cardiovascular, extravasated blood, stagnated blood and female diseases in traditional Chinese medicine (TCM). However, there are no reports on the anti-influenza virus activity of this species. Here, the anti-influenza virus activity of P. delavayi root extracts was first evaluated by an influenza virus neuraminidase (NA) inhibition assay. Meantime, constituents in the active extracts were identified using ultra-high performance liquid coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and seven major identified constituents were used to further evaluate the NA inhibitory activity. The results showed that the ethyl acetate fraction (EA) and the ethanol fraction (E) of P. delavayi both presented strong NA inhibitory activity with IC50 values of 75.932 μg/mL and 83.550 μg/mL, respectively. Twenty-seven constituents were characterized in these two active extracts by UPLC-Q-TOF-MS analysis, and seven major identified constituents exhibited high activity against the influenza virus. Among them, Benzoylpaeoniflorin (IC50 = 143.701 µM) and pentagalloylglucose (IC50 = 62.671 µM) exhibited the highest activity against the influenza virus, even far stronger than oseltamivir acid (IC50 = 281.308 µM). This study indicated that P. delavayi was a strong NA inhibitor, but cell-based inhibition, anti-influenza virus activity in vivo and anti-influenza virus mechanism still need to be tested and explored. PMID:27571059

  6. The anti-cancer activity of a cationic anti-microbial peptide derived from monomers of polyhydroxyalkanoate.

    PubMed

    O'Connor, Stephen; Szwej, Emilia; Nikodinovic-Runic, Jasmina; O'Connor, Aisling; Byrne, Annette T; Devocelle, Marc; O'Donovan, Norma; Gallagher, William M; Babu, Ramesh; Kenny, Shane T; Zinn, Manfred; Zulian, Qun Ren; O'Connor, Kevin E

    2013-04-01

    The biodegradable polymer medium chain length polyhydroxyalkanoate (mclPHA), produced by Pseudomonas putida CA-3, was depolymerised and the predominant monomer (R)-3-hydroxydecanoic acid (R10) purified. R10 was conjugated to a d-peptide DP18 and its derivatives. All peptides conjugated with R10 exhibited greater anti-cancer activity compared to the unconjugated peptides. Unconjugated and conjugated peptides were cytocidal for cancer cells. Conjugation of R10 to peptides was essential for enhanced anti-proliferation activity, as unconjugated mixes did not result in enhancement of anti-cancer activity. The conjugation of R10 resulted in more rapid uptake of peptides into HeLa and MiaPaCa cells compared to unconjugated peptide. Both unconjugated and R10 conjugated peptides localized to the mitochondria of HeLa and MiaPaCa cells and induced apoptosis. Peptide conjugated with a terminally hydroxylated decanoic acid (ω-hydroxydecanoic acid) exhibited 3.3 and 6.3 fold higher IC(50) values compared to R10 conjugated peptide indicating a role for the position of the hydroxyl moiety in enhancement of anti-cancer activity. Conjugation of decanoic acid (C10) to peptides resulted in similar or higher IC(50) values compared to R10 conjugates but C10 conjugates did not exhibit any cancer selectivity. Combination studies showed that R10DP18L exhibited synergy with cisplatin, gemcitabine, and taxotere with IC(50) values in the nanomolar range. PMID:23343631

  7. Screening of some Tanzanian medicinal plants for their trypanocidal and cytotoxic activities.

    PubMed

    Nibret, Endalkachew; Ashour, Mohamed L; Rubanza, Chrispinus D; Wink, Michael

    2010-06-01

    The objective of the present study was to evaluate in vitro antitrypanosomal and cytotoxic activities of crude extracts of 20 traditionally used medicinal plants of Tanzania. A total of 40 extracts (dichloromethane and methanol) were screened for antiproliferative activity of bloodstream form of T. b. brucei and human leukaemia HL-60 cell. Inhibition of cell proliferation was assessed using resazurin as vital stain. Of the 40 extracts tested, the dichloromethane extract from bark of Warburgia salutaris (Canellaceae) exhibited the most potent antitrypanosomal activity with an IC(50) value of 10.68 microg/ml. A dichloromethane extract from Lannea stuhlmannii (Anacardiaceae) was found to be the most cytotoxic extract against HL-60 (IC(50) = 27.15 microg/ml). Out of the 20 plants tested, 5 plants exhibited trypanocidal activity with IC(50) values below 20 microg/ml. These 5 plants: Entandrophragma bussei (Meliaceae), Securidaca longepedunculata (Polygalaceae), Warburgia salutaris (Canellaceae), Zanha africana (Sapindaceae) and Zanthoxylum chalybeum (Rutaceae) could therefore serve as sources of lead compounds for treatment of trypanosomiasis. PMID:19957246

  8. Prenylated benzoylphloroglucinols and xanthones from the leaves of Garcinia oblongifolia with antienteroviral activity.

    PubMed

    Zhang, Hong; Tao, Ling; Fu, Wen-Wei; Liang, Shuang; Yang, Yi-Fu; Yuan, Qing-Hong; Yang, Da-Jian; Lu, Ai-Ping; Xu, Hong-Xi

    2014-04-25

    An acetone extract of the leaves of Garcinia oblongifolia showed antiviral activity against enterovirus 71 (EV71) using a cytopathic effect inhibition assay. Bioassay-guided fractionation yielded 12 new prenylated benzoylphloroglucinols, oblongifolins J-U (1-12), and five known compounds. The structures of 1-12 were elucidated by spectroscopic analysis including 1D- and 2D-NMR and mass spectrometry methods. The absolute configurations were determined by a combination of a Mosher ester procedure carried out in NMR tubes and ECD calculations. Compared to ribavirin (IC50 253.1 μM), compounds 1, 4, and 13 exhibited significant anti-EV71 activity in vitro, with IC50 values of 31.1, 16.1, and 12.2 μM, respectively. In addition, the selectivity indices of these compounds were 1.5, 2.4, and 3.0 in African green monkey kidney (Vero) cells, respectively. PMID:24679044

  9. Two new phragmalin-type limonoids from Chukrasia tabularis and their α-glucosidase inhibitory activity.

    PubMed

    Peng, Jun-Lin; Wang, Jun; Mei, Wen-Li; Kong, Fan-Dong; Liu, Zi-Qi; Wang, Pei; Gai, Cui-Juan; Jiang, Bei; Dai, Hao-Fu

    2016-07-01

    Phytochemical investigation on the stems of C. tabularis (Meliaceae) led to the isolation of two new phragmalin-type limonoids, named tabularisins S and T (1-2), along with five known ones (3-7). The structures of the new limonoids were established by spectroscopic methods including UV, IR, HRESIMS, and 1D and 2D NMR. All the compounds were evaluated for α-glucosidase inhibitory activity in vitro. Compounds 2 and 3 exhibited significant inhibitory activity against α-glucosidase with IC50 values of 0.15 and 0.03 mM, respectively (acarbose as positive control, IC50 0.95 mM). PMID:26837821

  10. Antitrypanosomal Activities and Cytotoxicity of Some Novel Imido-substituted 1,4-Naphthoquinone Derivatives

    PubMed Central

    Khraiwesh, Mozna H.; Lee, Clarence M.; Brandy, Yakini; Akinboye, Emmanuel S.; Berhe, Solomon; Gittens, Genelle; Abbas, Muneer M.; Ampy, Franklin R.; Ashraf, Mohammad

    2013-01-01

    The antitrypanosomal activities, cytotoxicity, and selectivity indices of eleven imido-substituted 1,4-naphthoquinone derivatives and nifurtimox have been studied. Compared to nifurtimox (IC50 = 10.67 µM), all the imido-naphthoquinone analogs (IMDNQ1-IMDNQ11) are more potent on Trypanosoma cruzi with IC50 values ranging from 0.7 µM to 6.1 µM (p < 0.05). Studies of the cytotoxic activities of these compounds on a Balb/C 3T3 mouse fibroblast cell line revealed that four of these compounds, IMDNQ1, IMDNQ2, IMDNQ3, and IMDNQ10 displayed selectivity indices of 60.25, 53.97, 31.83, and 275.3, respectively, rendering them significantly (p < 0.05) more selective in inhibiting the parasite growth than nifurtimox (selectivity index = 10.86). PMID:22297740

  11. Antitrypanosomal activities and cytotoxicity of some novel imido-substituted 1,4-naphthoquinone derivatives.

    PubMed

    Khraiwesh, Mozna H; Lee, Clarence M; Brandy, Yakini; Akinboye, Emmanuel S; Berhe, Solomon; Gittens, Genelle; Abbas, Muneer M; Ampy, Franklin R; Ashraf, Mohammad; Bakare, Oladapo

    2012-01-01

    The antitrypanosomal activities, cytotoxicity, and selectivity indices of eleven imido-substituted 1,4-naphthoquinone derivatives and nifurtimox have been studied. Compared to nifurtimox (IC(50) = 10.67 μM), all the imido-naphthoquinone analogs (IMDNQ1-IMDNQ11) are more potent on Trypanosoma cruzi with IC50 values ranging from 0.7 μM to 6.1 μM (p < 0.05). Studies of the cytotoxic activities of these compounds on a Balb/C 3T3 mouse fibroblast cell line revealed that four of these compounds, IMDNQ1, IMDNQ2, IMDNQ3, and IMDNQ10 displayed selectivity indices of 60.25, 53.97, 31.83, and 275.3, respectively, rendering them significantly (p < 0.05) more selective in inhibiting the parasite growth than nifurtimox (selectivity index = 10.86). PMID:22297740

  12. Discovery of KDM5A inhibitors: Homology modeling, virtual screening and structure-activity relationship analysis.

    PubMed

    Wu, Xiaoai; Fang, Zhen; Yang, Bo; Zhong, Lei; Yang, Qiuyuan; Zhang, Chunhui; Huang, Shenzhen; Xiang, Rong; Suzuki, Takayoshi; Li, Lin-Li; Yang, Sheng-Yong

    2016-05-01

    Herein we report the discovery of a series of new KDM5A inhibitors. A three-dimensional (3D) structure model of KDM5A jumonji domain was firstly established based on homology modeling. Molecular docking-based virtual screening was then performed against commercial chemical databases. A number of hit compounds were retrieved. Further structural optimization and structure-activity relationship (SAR) analysis were carried out to the most active hit compound, 9 (IC50: 2.3μM), which led to the discovery of several new KDM5A inhibitors. Among them, compound 15e is the most potent one with an IC50 value of 0.22μM against KDM5A. This compound showed good selectivity for KDM5A and considerable ability to suppress the demethylation of H3K4me3 in intact cells. Compound 15e could be taken as a good lead compound for further studies. PMID:27020306

  13. Synthesis and antikinetoplastid activities of 3-substituted quinolinones derivatives.

    PubMed

    Audisio, Davide; Messaoudi, Samir; Cojean, Sandrine; Peyrat, Jean-François; Brion, Jean-Daniel; Bories, Christian; Huteau, Françoise; Loiseau, Philippe M; Alami, Mouad

    2012-06-01

    A new family of quinolinone derivatives has been synthesized and evaluated for their antikinetoplastid activities against Leishmania donovani and Trypanosoma brucei brucei. Results from these structure-activity relationship studies enabled identification of compounds 3a and 4g as the most active compounds against L. donovani promastigotes and amastigotes parasites (IC(50) values in a range of 2-11 μM). Additionally, compound 3b has emerged from this study as the most active compound in the series against T. b. brucei with a MEC value of 12 μM. These three compounds are worth of further in vivo evaluation. PMID:22472166

  14. Comparison of in vitro hormone activities of novel flame retardants TBB, TBPH and their metabolites TBBA and TBMEPH using reporter gene assays.

    PubMed

    Klopčič, Ivana; Skledar, Darja Gramec; Mašič, Lucija Peterlin; Dolenc, Marija Sollner

    2016-10-01

    The anti-androgenic and anti-thyroid hormonal activities of the two novel brominated flame retardants, TBB and TBPH and of their metabolites TBBA and TBMEPH have been compared using the luciferase reporter gene assays. Only the parent compounds TBB and TBPH exhibited anti-glucocorticoid activity with IC50 values of 1.9 μM and 0.3 μM. Furthermore, mode of action for these two compounds is by direct competing to the glucocorticoid receptor (GR) with IC50 values of 0.03 μM and 0.002 μM. All four tested compounds possess anti-androgenic and anti-thyroid hormonal activities, without agonist activities on the respective receptors. Anti-androgenic activities with IC50 values of 43.5 μM, 0.1 μM, 47.5 μM and 1.3 μM were found for TBB, TBPH, TBBA and TBMEPH. The anti-thyroid hormonal IC50 values of 37.5 μM, 0.1 μM, 22.8 μM and 32.3 μM for TBB, TBPH, TBBA and TBMEPH, together with the above quoted results, indicate that metabolism can modify anti-androgenic, anti-glucocorticoid and anti-thyroid hormonal effects of these novel brominated flame retardants. Furthermore, the parent flame retardants are shown to be able to disrupt the function of the GR as antagonists by direct competition to the receptor. PMID:27380226

  15. The Interplay of Scientific Activity, Worldviews and Value Outlooks

    ERIC Educational Resources Information Center

    Lacey, Hugh

    2009-01-01

    Scientific activity tends to reflect particular worldviews and their associated value outlooks; and scientific results sometimes have implications for worldviews and the presuppositions of value outlooks. Even so, scientific activity per se neither presupposes nor provides sound rational grounds to accept any worldview or value outlook. Moreover,…

  16. Active compounds from a diverse library of triazolothiadiazole and triazolothiadiazine scaffolds: synthesis, crystal structure determination, cytotoxicity, cholinesterase inhibitory activity, and binding mode analysis.

    PubMed

    Khan, Imtiaz; Ibrar, Aliya; Zaib, Sumera; Ahmad, Sarfraz; Furtmann, Norbert; Hameed, Shahid; Simpson, Jim; Bajorath, Jürgen; Iqbal, Jamshed

    2014-11-01

    In an effort to identify novel cholinesterase candidates for the treatment of Alzheimer's disease (AD), a diverse array of potentially bioactive compounds including triazolothiadiazoles (4a-h and 5a-f) and triazolothiadiazines (6a-h) was obtained in good yields through the cyclocondensation reaction of 4-amino-5-(pyridin-3-yl)-4H-1,2,4-triazole-3-thiol (3) with various substituted aryl/heteroaryl/aryloxy acids and phenacyl bromides, respectively. The structures of newly prepared compounds were confirmed by IR, (1)H and (13)C NMR spectroscopy and, in case of 4a, by single crystal X-ray diffraction analysis. The purity of the synthesized compounds was ascertained by elemental analysis. The newly synthesized conjugated heterocycles were screened for cholinesterase inhibitory activity against electric eel acetylcholinesterase (EeAChE) and horse serum butyrylcholinesterase (hBChE). Among the evaluated hybrids, several compounds were identified as potent inhibitors. Compounds 5b and 5d were most active with an IC50 value of 3.09 ± 0.154 and 11.3 ± 0.267 μM, respectively, against acetylcholinesterase, whereas 5b, 6a and 6g were most potent against butyrylcholinesterase, with an IC50 of 0.585 ± 0.154, 0.781 ± 0.213, and 1.09 ± 0.156 μM, respectively, compared to neostigmine and donepezil as standard drugs. The synthesized heteroaromatic compounds were also tested for their cytotoxic potential against lung carcinoma (H157) and vero cell lines. Among them, compound 6h exhibited highest antiproliferative activity against H157 cell lines, with IC50 value of 0.96 ± 0.43 μM at 1mM concentration as compared to vincristine (IC50=1.03 ± 0.04 μM), standard drug used in this study. PMID:25257911

  17. Abalone Protein Hydrolysates: Preparation, Angiotensin I Converting Enzyme Inhibition and Cellular Antioxidant Activity

    PubMed Central

    Park, Soo Yeon; Je, Jae-Young; Hwang, Joung-Youl; Ahn, Chang-Bum

    2015-01-01

    Abalone protein was hydrolyzed by enzymatic hydrolysis and the optimal enzyme/substrate (E/S) ratios were determined. Abalone protein hydrolysates (APH) produced by Protamex at E/S ratio of 1:100 showed angiotensin I converting enzyme inhibitory activity with IC50 of 0.46 mg/mL, and APH obtained by Flavourzyme at E/S ratio of 1:100 possessed the oxygen radical absorbance capacity value of 457.6 μM trolox equivalent/mg sample. Flavourzyme abalone protein hydrolysates (FAPH) also exhibited H2O2 scavenging activity with IC50 of 0.48 mg/mL and Fe2+ chelating activity with IC50 of 2.26 mg/mL as well as high reducing power. FAPH significantly (P<0.05) protected H2O2-induced hepatic cell damage in cultured hepatocytes, and the cell viability was restored to 90.27% in the presence of FAPH. FAPH exhibited 46.20% intracellular ROS scavenging activity and 57.89% lipid peroxidation inhibition activity in cultured hepatocytes. Overall, APH may be useful as an ingredient for functional foods. PMID:26451354

  18. One Pot Selective Arylation of 2-Bromo-5-Chloro Thiophene; Molecular Structure Investigation via Density Functional Theory (DFT), X-ray Analysis, and Their Biological Activities

    PubMed Central

    Rasool, Nasir; Kanwal, Aqsa; Rasheed, Tehmina; Ain, Quratulain; Mahmood, Tariq; Ayub, Khurshid; Zubair, Muhammad; Khan, Khalid Mohammed; Arshad, Muhammad Nadeem; M. Asiri, Abdullah; Zia-Ul-Haq, Muhammad; Jaafar, Hawa Z. E.

    2016-01-01

    Synthesis of 2,5-bisarylthiophenes was accomplished by sequential Suzuki cross coupling reaction of 2-bromo-5-chloro thiophenes. Density functional theory (DFT) studies were carried out at the B3LYP/6-31G(d, p) level of theory to compare the geometric parameters of 2,5-bisarylthiophenes with those from X-ray diffraction results. The synthesized compounds are screened for in vitro bacteria scavenging abilities. At the concentration of 50 and 100 μg/mL, compounds 2b, 2c, 2d, 3c, and 3f with IC50-values of 51.4, 52.10, 58.0, 56.2, and 56.5 μg/mL respectively, were found most potent against E. coli. Among all the synthesized compounds 2a, 2d, 3c, and 3e with the least values of IC50 77, 76.26, 79.13 μg/mL respectively showed significant antioxidant activities. Almost all of the compounds showed good antibacterial activity against Escherichia coli, whereas 2-chloro-5-(4-methoxyphenyl) thiophene (2b) was found most active among all synthesized compound with an IC50 value of 51.4 μg/mL. All of the synthesized compounds were screened for nitric oxide scavenging activity as well. Frontier molecular orbitals (FMOs) and molecular electrostatic potentials of the target compounds were also studied theoretically to account for their relative reactivity PMID:27367666

  19. Antioxidant activity of lignin phenolic compounds as by-product of pretreatment process of bioethanol production from empty fruits palm bunch

    NASA Astrophysics Data System (ADS)

    Meliana, Y.; Setiawan, A. H.

    2016-02-01

    As by-product of pretreatment bioethanol production, ligno-cellulosic biomass creates an abundance of bioresidue. This work is devoted to studies the antioxidant activity of lignin that obtained from recovery process of bioethanol by-product. This by-product comes from pretreatment process of empty fruit palm bunch in acid (pH 2) and alkaline (pH 12) conditions. The samples of purified lignin were characterized by Fourier Transform Infrared (FTIR) and Particle Size Analyzer (PSA). Radical scavenging efficiency of lignin was examined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method using quercetin as a standard. The value of IC50 showed that the lignin that was purified in acid condition (pH 2) gave the activity value in antioxidant active range (IC50 sample Lignin pH 2 = 69.41), on the other hand the lignin that was purified in alkaline condition (Lignin pH 12) did not have the activity value as an antioxidant (IC50 sample Lignin pH 12 = NA).

  20. One Pot Selective Arylation of 2-Bromo-5-Chloro Thiophene; Molecular Structure Investigation via Density Functional Theory (DFT), X-ray Analysis, and Their Biological Activities.

    PubMed

    Rasool, Nasir; Kanwal, Aqsa; Rasheed, Tehmina; Ain, Quratulain; Mahmood, Tariq; Ayub, Khurshid; Zubair, Muhammad; Khan, Khalid Mohammed; Arshad, Muhammad Nadeem; M Asiri, Abdullah; Zia-Ul-Haq, Muhammad; Jaafar, Hawa Z E

    2016-01-01

    Synthesis of 2,5-bisarylthiophenes was accomplished by sequential Suzuki cross coupling reaction of 2-bromo-5-chloro thiophenes. Density functional theory (DFT) studies were carried out at the B3LYP/6-31G(d, p) level of theory to compare the geometric parameters of 2,5-bisarylthiophenes with those from X-ray diffraction results. The synthesized compounds are screened for in vitro bacteria scavenging abilities. At the concentration of 50 and 100 μg/mL, compounds 2b, 2c, 2d, 3c, and 3f with IC50-values of 51.4, 52.10, 58.0, 56.2, and 56.5 μg/mL respectively, were found most potent against E. coli. Among all the synthesized compounds 2a, 2d, 3c, and 3e with the least values of IC50 77, 76.26, 79.13 μg/mL respectively showed significant antioxidant activities. Almost all of the compounds showed good antibacterial activity against Escherichia coli, whereas 2-chloro-5-(4-methoxyphenyl) thiophene (2b) was found most active among all synthesized compound with an IC50 value of 51.4 μg/mL. All of the synthesized compounds were screened for nitric oxide scavenging activity as well. Frontier molecular orbitals (FMOs) and molecular electrostatic potentials of the target compounds were also studied theoretically to account for their relative reactivity. PMID:27367666

  1. Top-down Targeted Metabolomics Reveals a Sulfur-Containing Metabolite with Inhibitory Activity against Angiotensin-Converting Enzyme in Asparagus officinalis.

    PubMed

    Nakabayashi, Ryo; Yang, Zhigang; Nishizawa, Tomoko; Mori, Tetsuya; Saito, Kazuki

    2015-05-22

    The discovery of bioactive natural compounds containing sulfur, which is crucial for inhibitory activity against angiotensin-converting enzyme (ACE), is a challenging task in metabolomics. Herein, a new S-containing metabolite, asparaptine (1), was discovered in the spears of Asparagus officinalis by targeted metabolomics using mass spectrometry for S-containing metabolites. The contribution ratio (2.2%) to the IC50 value in the crude extract showed that asparaptine (1) is a new ACE inhibitor. PMID:25922884

  2. Potential xanthine oxidase inhibitory activity of endophytic Lasiodiplodia pseudotheobromae.

    PubMed

    Kapoor, Neha; Saxena, Sanjai

    2014-07-01

    Xanthine oxidase is considered as a potential target for treatment of hyperuricemia. Hyperuricemia is predisposing factor for gout, chronic heart failure, atherosclerosis, tissue injury, and ischemia. To date, only two inhibitors of xanthine oxidase viz. allopurinol and febuxostat have been clinically approved for used as drugs. In the process of searching for new xanthine oxidase inhibitors, we screened culture filtrates of 42 endophytic fungi using in vitro qualitative and quantitative XO inhibitory assays. The qualitative assay exhibited potential XO inhibition by culture filtrates of four isolates viz. #1048 AMSTITYEL, #2CCSTITD, #6AMLWLS, and #96 CMSTITNEY. The XO inhibitory activity was present only in the chloroform extract of the culture filtrates. Chloroform extract of culture filtrate #1048 AMSTITYEL exhibited the highest inhibition of XO with an IC50 value of 0.61 μg ml(-1) which was better than allopurinol exhibiting an IC50 of 0.937 μg ml(-1) while febuxostat exhibited a much lower IC50 of 0.076 μg ml(-1). Further, molecular phylogenetic tools and morphological studies were used to identify #1048 AMSTITYEL as Lasiodiplodia pseudotheobromae. This is the first report of an endophytic Lasiodiplodia pseudotheobromae from Aegle marmelos exhibiting potential XO Inhibitory activity. PMID:24801403

  3. New insights into 3-(aminomethyl)naphthoquinones: Evaluation of cytotoxicity, electrochemical behavior and search for structure-activity correlation.

    PubMed

    da Silva, Gustavo B; Neves, Amanda P; Vargas, Maria D; Marinho-Filho, José D B; Costa-Lotufo, Letícia V

    2016-08-01

    Herein we describe the structure-activity relationship of a large library of Mannich bases (MBs) synthesized from 2-hydroxy-1,4-naphthoquinone. In general, the compounds have shown high to moderate activity against the HL-60 (promyelocytic leukaemia) cell line with IC50=1.1-19.2μM. Our results suggest that the nature of the aryl moiety introduced in the structure of MBs by the aldehyde component is crucial to the cytotoxicity, and although the group originated from the primary amine has a lesser influence, aromatic ones were found to suppress the activity. Thus, MBs derived from salicylaldehydes or 2-pyridinecarboxaldehyde and aliphatic amines are the most active compounds. A satisfactory correlation of the EpIIc versus IC50 (μM) in dimethylsulfoxide was observed. The most cytotoxic MBs (Series a-c, derived from salicylaldehydes) showed the least negative EpIIc values. Noteworthy, however, Series d (derived from 2-pyridinecarboxaldehyde) did not follow this correlation. They exhibited both the lowest IC50 and the most negative EpIIc values, thus suggesting that other factors also influence the cytotoxicity of the MBs, such as lipophilicity, electronic distribution and hydrogen bonding. PMID:27363939

  4. Polyketides from the Mangrove-Derived Endophytic Fungus Nectria sp. HN001 and Their α-Glucosidase Inhibitory Activity

    PubMed Central

    Cui, Hui; Liu, Yayue; Nie, Yang; Liu, Zhaoming; Chen, Senhua; Zhang, Zhengrui; Lu, Yongjun; He, Lei; Huang, Xishan; She, Zhigang

    2016-01-01

    Four new polyketides: nectriacids A–C (1–3) and 12-epicitreoisocoumarinol (4), together with three known compounds: citreoisocoumarinol (5), citreoisocoumarin (6), and macrocarpon C (7) were isolated from the culture of the endophytic fungus Nectria sp. HN001, which was isolated from a fresh branch of the mangrove plant Sonneratia ovata collected from the South China Sea. Their structures were determined by the detailed analysis of NMR and mass spectroscopic data. The absolute configuration of the stereogenic carbons for compound 4 was further assigned by Mosher’s ester method. All of the isolated compounds were tested for their α-glucosidase inhibitory activity by UV absorbance at 405 nm, and new compounds 2 and 3 exhibited potent inhibitory activity with IC50 values of 23.5 and 42.3 μM, respectively, which were more potent than positive control (acarbose, IC50, 815.3 μM). PMID:27136568

  5. Polyketides from the Mangrove-Derived Endophytic Fungus Nectria sp. HN001 and Their α-Glucosidase Inhibitory Activity.

    PubMed

    Cui, Hui; Liu, Yayue; Nie, Yang; Liu, Zhaoming; Chen, Senhua; Zhang, Zhengrui; Lu, Yongjun; He, Lei; Huang, Xishan; She, Zhigang

    2016-05-01

    Four new polyketides: nectriacids A-C (1-3) and 12-epicitreoisocoumarinol (4), together with three known compounds: citreoisocoumarinol (5), citreoisocoumarin (6), and macrocarpon C (7) were isolated from the culture of the endophytic fungus Nectria sp. HN001, which was isolated from a fresh branch of the mangrove plant Sonneratia ovata collected from the South China Sea. Their structures were determined by the detailed analysis of NMR and mass spectroscopic data. The absolute configuration of the stereogenic carbons for compound 4 was further assigned by Mosher's ester method. All of the isolated compounds were tested for their α-glucosidase inhibitory activity by UV absorbance at 405 nm, and new compounds 2 and 3 exhibited potent inhibitory activity with IC50 values of 23.5 and 42.3 μM, respectively, which were more potent than positive control (acarbose, IC50, 815.3 μM). PMID:27136568

  6. Evaluation of antioxidant activity and preventing DNA damage effect of pomegranate extracts by chemiluminescence method.

    PubMed

    Guo, Shanshan; Deng, Qianchun; Xiao, Junsong; Xie, Bijun; Sun, Zhida

    2007-04-18

    The antioxidant activities of three parts (peel, juice, and seed) and extracts of three pomegranate varieties in China were investigated by using a chemiluminescence (CL) method in vitro. The scavenging ability of pomegranate extracts (PEs) on superoxide anion, hydroxide radical, and hydrogen peroxide was determined by the pyrogallol-luminol system, the CuSO4-Phen-Vc-H2O2 system, and the luminol-H2O2 system, respectively. DNA damage preventing the effect of PE was determined by the CuSO4-Phen-Vc-H2O2-DNA CL system. The results showed that the peel extract of red pomegranate had the best effect on the scavenging ability of superoxide anion because its IC50 value (4.01 +/- 0.09 microg/mL) was the lowest in all PEs. The seed extract of white pomegranate could scavenge hydroxide radical most effectively of the nine extracts (the IC50 value was 1.69 +/- 0.03 microg/mL). The peel extract of white pomegranate had the best scavenging ability on hydrogen peroxide, which had the lowest IC50 value (0.032 +/- 0.003 microg/mL) in the nine extracts. The seed extract of white pomegranate (the IC50 value was 3.67 +/- 0.03 microg/mL) was the most powerful on the DNA damage-preventing effect in all of the PEs. Also, the statistical analysis indicated that there were significant differences (at P < 0.05) among the extracts of the different varieties and parts in each system. PMID:17381116

  7. Composition and Biological Activity of Volatile Oil from Salviajudaica and S. multicaulis from Jordan.

    PubMed

    Afifi, Fatma U; Kasabri, Violet; Al-Jaber, Hala I; Abu-Irmaileh, Barakat E; Al-Qudah, Mahmoud A; Abazaa, Ismail F

    2016-04-01

    The aim of this work was to determine the composition of the hydro-distilled essential oil of Salvia judaica Boiss. and S. multicaulis Vahl. (Lamiaceae) from Jordan by GC and GC-MS and to report the actual composition of their fresh leaves and flowers using SPME (Solid Phase Micro-Extraction).Their dual alpha-amylase/alpha glucosidase and pancreatic lipase inhibitory activities as well as their anti-proliferative potential were screened. The aroma profile of the leaves, flowers, and flowers at pre-flowering stages of S. judaica, obtained through SPME was composed of sesquiterpene hydrocarbons (87.7 %, 71.8 %, and 86.2 %, respectively) while the hydro-distilled oil of the dry leaves was rich in oxygenated sesquiterpenes (50.8%). Fresh leaves of S. multicaulis were rich in oxygenated monoterpenes (58.1%), while monoterpene hydrocarbons dominated the blooming flowers (57.2%) and the flowers at the pre-flowering stage (64.7%). The hydro-distilled oil of the dry leaves was rich in oxygenated monoterpenes (77.6%). With doxorubicin as a positive control, no anti-proliferative activity was observed against colorectal cancer cell lines HT29, HCT116, and SW620 using SRB assay for either Salvia spp. In vitro enzymatic starch digestion was evaluated with Acarbose (IC50: 0.2 ± 0.0 µg /mL) as the reference drug. The respective IC50 (mg/mL) values of S. judaica and S. multicaulis aqueous extracts were 4.9 ± 0.4 and 10.3 ± 0.9. Modulation of pancreatic lipase activity (PL) was determined by colorimetry and compared with Orlistat (IC50 : 0.11 ± 0.0 µg/mL). PL-IC50 values (µg/mL) obtained for S. judaica and S. multicaulis were 108.5±6.4 and 31.8 ± 0.8, respectively. PMID:27396212

  8. Abietane-Type Diterpenoid Amides with Highly Potent and Selective Activity against Leishmania donovani and Trypanosoma cruzi.

    PubMed

    Pirttimaa, Minni; Nasereddin, Abedelmajeed; Kopelyanskiy, Dmitry; Kaiser, Marcel; Yli-Kauhaluoma, Jari; Oksman-Caldentey, Kirsi-Marja; Brun, Reto; Jaffe, Charles L; Moreira, Vânia M; Alakurtti, Sami

    2016-02-26

    Dehydroabietylamine (1) was used as a starting material to synthesize a small library of dehydroabietyl amides by simple and facile methods, and their activities against two disease-causing trypanosomatids, namely, Leishmania donovani and Trypanosoma cruzi, were assayed. The most potent compound, 10, an amide of dehydroabietylamine and acrylic acid, was found to be highly potent against these parasites, displaying an IC50 value of 0.37 μM against L. donovani axenic amastigotes and an outstanding selectivity index of 63. Moreover, compound 10 fully inhibited the growth of intracellular amastigotes in Leishmania donovani-infected human macrophages with a low IC50 value of 0.06 μM. This compound was also highly effective against T. cruzi amastigotes residing in L6 cells with an IC50 value of 0.6 μM and high selectivity index of 58, being 3.5 times more potent than the reference compound benznidazole. The potent activity of this compound and its relatively low cytotoxicity make it attractive for further development in pursuit of better drugs for patients suffering from leishmaniasis and Chagas disease. PMID:26849852

  9. Inhibition of chemiluminescence and chemotactic activity of phagocytes in vitro by the extracts of selected medicinal plants.

    PubMed

    Jantan, Ibrahim; Harun, Nurul Hikmah; Septama, Abdi Wira; Murad, Shahnaz; Mesaik, M A

    2011-04-01

    The methanol extracts of 20 selected medicinal plants were investigated for their effects on the respiratory burst of human whole blood, isolated human polymorphonuclear leukocytes (PMNs) and isolated mice macrophages using a luminol/lucigenin-based chemiluminescence assay. We also tested the effect of the extracts on chemotactic migration of PMNs using the Boyden chamber technique. The extracts of Curcuma domestica L., Phyllanthus amarus Schum & Thonn and C. xanthorrhiza Roxb. were the samples producing the strongest oxidative burst of PMNs with luminol-based chemiluminescence, with IC(50) values ranging from 0.5 to 0.7 μg/ml. For macrophage cells, the extracts which showed strong suppressive activity for luminol-based chemiluminescence were C. xanthorrhiza and Garcinia mangostana L. Among the extracts studied, C. mangga Valton & Vazsjip, Piper nigrum L. and Labisia pumila var. alata showed strong inhibitory activity on lucigenin-amplified oxidative burst of PMNs, with IC(50) values ranging from 0.9 to 1.5 μg/ml. The extracts of Zingiber officinale Rosc., Alpinia galangal (L.) Willd and Averrhoa bilimbi Linn showed strong inhibition on the chemotaxic migration of cells, with IC(50) values comparable to that of ibuprofen (1.5 μg/ml). The results suggest that some of these plants were able to modulate the innate immune response of phagocytes at different steps, emphasizing their potential as a source of new immunomodulatory agents. PMID:21184195

  10. Quality assessment and antiplasmodial activity of West African Cochlospermum species.

    PubMed

    Lamien-Meda, Aline; Kiendrebeogo, Martin; Compaoré, Moussa; Meda, Roland N T; Bacher, Markus; Koenig, Karin; Pacher, Thomas; Fuehrer, Hans-Peter; Noedl, Harald; Willcox, Merlin; Novak, Johannes

    2015-11-01

    The present study focuses on development of phytochemical methods for quality assessment of two West-African Cochlospermum species (Cochlospermum planchonii and Cochlospermum tinctorium) traditionally used for malaria treatment in Burkina Faso. Antimalarial activity of preparations from dried rhizomes (decoction) was tested against the chloroquine-sensitive Plasmodium strain 3D7 using the histidine-rich protein II (HRP2) drug susceptibility assay and compared with extract preparations using organic solvents of different polarity. Two main apocarotenoids were isolated from rhizomes of C. planchonii and unambiguously identified as dihydrocochloxanthine and cochloxanthine by spectroscopic methods. Comparative HPLC analyses of thirty-nine (39) samples from markets and from collections in natural habitats of both species showed a high variability in the accumulation of cochloxanthines and related carotenoids which were proven to be characteristic for rhizomes of both species and generally absent in leaves. Furthermore, content of total phenolics and antioxidant activities (DPPH and FRAP) as well as haemolytic activity of various extracts was tested. The HPLC method presented here was validated and provides a good separation of both compounds including 10 minor carotenoids. Extracts from both species and pure cochloxanthine offered pronounced antioxidant activities and weak haemolytic activity while, in contrast, dihydrocochloxanthine had a strong haemolytic effect at the highest concentration analysed. However, cochloxanthine as well as dihydrocochloxanthine showed erythroprotective effects against the haemolytic activity of the reference saponin. Moderate antiplasmodial activity between 16 and 63 μg/ml were observed with all tested extracts, and lower IC50 values were obtained with pure dihydrocochloxanthine (IC50=6.9 μg/ml), cochloxanthine (IC50=6.8 μg/ml), the DCM fraction (IC50=2.4 μg/ml) and the ethyl acetate fraction (IC50=11.5μg/ml) derived from a methanolic

  11. In vitro antioxidant activity and total phenolic content of ethanolic leaf extract of Stevia rebaudiana Bert.

    PubMed

    Shukla, Shruti; Mehta, Archana; Bajpai, Vivek K; Shukla, Savita

    2009-09-01

    The aim of this study was to assess the in vitro potential of ethanolic leaf extract of Stevia rebaudiana as a natural antioxidant. The DPPH activity of the extract (20, 40, 50, 100 and 200 microg/ml) was increased in a dose dependent manner, which was found in the range of 36.93-68.76% as compared to ascorbic acid 64.26-82.58%. The IC(50) values of ethanolic extract and ascorbic acid in DPPH radical scavenging assay were obtained to be 93.46 and 26.75 microg/ml, respectively. The ethanolic extract was also found to scavenge the superoxide generated by EDTA/NBT system. Measurement of total phenolic content of the ethanolic extract of S. rebaudiana was achieved using Folin-Ciocalteau reagent containing 61.50 mg/g of phenolic content, which was found significantly higher when compared to reference standard gallic acid. The ethanolic extract also inhibited the hydroxyl radical, nitric oxide, superoxide anions with IC(50) values of 93.46, 132.05 and 81.08 microg/ml, respectively. However, the IC(50) values for the standard ascorbic acid were noted to be 26.75, 66.01 and 71.41 microg/ml respectively. The results obtained in this study clearly indicate that S. rebaudiana has a significant potential to use as a natural antioxidant agent. PMID:19540900

  12. Evaluation of in vitro antimalarial activity of different extracts of Artemisia aucheri Boiss. and A. armeniaca Lam. and fractions of the most potent extracts.

    PubMed

    Mojarrab, Mahdi; Shiravand, Ali; Delazar, Abbas; Heshmati Afshar, Fariba

    2014-01-01

    Ten extracts with different polarity from two Iranian Artemisia species, A. armeniaca Lam. and A. aucheri Boiss, were screened for their antimalarial properties by in vitro   β -hematin formation assay. Dichloromethane (DCM) extracts of both plants showed significant antimalarial activities with IC50 values of 1.36±0.01 and 1.83±0.03 mg/mL and IC90 values of 2.12±0.04 and 2.62±0.09 mg/mL for A. armeniaca and A. aucheri, respectively. Bioactivity-guided fractionation of DCM extracts of both plants by vacuum liquid chromatography (VLC) over silica gel with solvent mixtures of increasing polarities afforded seven fractions. Two fractions from DCM extract of A. armeniaca and four fractions from DCM extract of A. aucheri showed potent antimalarial activity with reducing IC50 and IC90 values compared to extracts. The most potent fraction belonged to DCM extract of A. armeniaca with IC50 and IC90 values of 0.47±0.006 and 0.71±0.006 mg/mL, respectively. PMID:24558335

  13. Molecular design, synthesis and anticoagulant activity evaluation of fluorinated dabigatran analogues.

    PubMed

    Wang, Fei; Ren, Yu-Jie; Dong, Ming-Hui

    2016-06-15

    In the present study, a series of unreported fluorinated dabigatran analogues, which were based on the structural scaffold of dabigatran, were designed by computer-aided simulation. Fifteen fluorinated dabigatran analogues were screened and synthesized. All target compounds were characterized by (1)H NMR, (13)C NMR, (19)F NMR and HRMS. According to the preliminary screening results of inhibition ratio, eleven analogues (inhibition ratio >90%) were evaluated for antithrombin activity in vitro (IC50). The test results expressed that all the analogues showed effective inhibitory activities against thrombin. Especially, compounds 8f, 8k and 8o, with IC50 values of 1.81, 3.21 and 2.16nM, respectively, showed remarkable anticoagulant activities which were in the range of reference drug dabigatran (IC50=1.23nM). Moreover, compounds 8k and 8o were developed to investigate their anticoagulant activities in vivo. In those part, compound 8o exhibited a fairly strong inhibitory action for arteriovenous thrombosis with inhibition ratio of 84.66%, which was comparable with that of dabigatran (85.07%). Docking simulations demonstrated that these compounds could act as candidates for further development of novel anticoagulant drugs. PMID:27166573

  14. In vitro antiviral activity of chestnut and quebracho woods extracts against avian reovirus and metapneumovirus.

    PubMed

    Lupini, C; Cecchinato, M; Scagliarini, A; Graziani, R; Catelli, E

    2009-12-01

    Field evidences have suggested that a natural extract, containing tannins, could be effective against poultry enteric viral infections. Moreover previous studies have shown that vegetable tannins can have antiviral activity against human viruses. Based on this knowledge three different Chestnut (Castanea spp.) wood extracts and one Quebracho (Schinopsis spp.) wood extract, all containing tannins and currently used in the animal feed industry, were tested for in vitro antiviral activity against avian reovirus (ARV) and avian metapneumovirus (AMPV). The MTT assay was used to evaluate the 50% cytotoxic compounds concentration (CC(50)) on Vero cells. The antiviral properties were tested before and after the adsorption of the viruses to Vero cells. Antiviral activities were expressed as IC(50) (concentration required to inhibit 50% of viral cytopathic effect). CC(50)s of tested compounds were > 200 microg/ml. All compounds had an extracellular antiviral effect against both ARV and AMPV with IC(50) values ranging from 25 to 66 microg/ml. Quebracho extract had also evident intracellular anti-ARV activity (IC(50) 24 microg/ml). These preliminary results suggest that the examined vegetable extracts might be good candidates in the control of some avian virus infections. Nevertheless further in vivo experiments are required to confirm these findings. PMID:19435637

  15. Anti-inflammatory and anti-proliferative activities of the wild edible cruciferous: Diplotaxis simplex.

    PubMed

    Jdir, Hamida; Khemakham, Bassem; Najjaa, Hanen; Chakroun, Mouna; Jridi, Mourad; Ben Arfa, Abdelkarim; Ben Ali, Yassine; Zouari, Nacim

    2016-10-01

    Context The present study deals with new biological properties of the wild edible Diplotaxis simplex (Viv.) Spreng (Brassicaceae). Objectives The current study evaluates the antioxidant, the anti-inflammatory and the anti-cancer properties of ethyl acetate and ethanol extracts from D. simplex flowers. Materials and methods The anti-proliferative activity of the extracts (10-70 μg/mL) was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) against human colon cancer cell line Caco-2. The anti-inflammatory potential was evaluated by the inhibitory effect of the extracts (1.5-7.5 mg/mL) on phospholipase A2 activity as well as on carrageenan-induced paw oedema in mice. Extracts (200 mg/kg) or indomethacin (50 mg/kg) as positive control were injected intraperitoneally for albino mice prior to the induction of the oedema by carrageenan. Antioxidant activities were investigated using various complementary methods. Results Flower extracts contained a high level of polyphenolics (17.10-52.70 mg GAE/g) and flavonoids (74.20-100.60 mg QE/g), which correlate with its appreciable antioxidant potential in β-carotene peroxidation (IC50 value: 12.50-27.10 μg/mL), DPPH(•) radical-scavenging (IC50 value: 0.20-0.40 mg/mL), Fe(3+ )reducing (EC50 value: 0.10-0.14 mg/mL) and Fe(2+ )chelating (IC50 value: 0.20-0.60 mg/mL) assays. These extracts were effective in inhibiting cancer cell growth (IC50 value: 62.0-63.25 μg/mL). Besides, the ethyl acetate extract inhibited phospholipase A2 activity (IC50 value: 2.97 mg/mL) and reduced the paw oedema in mice (from 0.38 ± 0.01 to 0.24 ± 0.01 cm), 4 h post-carrageenan challenge. Conclusion These data suggest that D. simplex may be useful as a candidate in the treatment of inflammation and the colon cancer. PMID:26916801

  16. Antileukemic activity of the HSP70 inhibitor pifithrin-μ in acute leukemia.

    PubMed

    Kaiser, M; Kühnl, A; Reins, J; Fischer, S; Ortiz-Tanchez, J; Schlee, C; Mochmann, L H; Heesch, S; Benlasfer, O; Hofmann, W-K; Thiel, E; Baldus, C D

    2011-07-01

    Heat shock protein (HSP) 70 is aberrantly expressed in different malignancies and has emerged as a promising new target for anticancer therapy. Here, we analyzed the in vitro antileukemic effects of pifithrin-μ (PFT-μ), an inhibitor of inducible HSP70, in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) cell lines, as well as in primary AML blasts. PFT-μ significantly inhibited cell viability at low micromolar concentrations in all cell lines tested, with IC50 values ranging from 2.5 to 12.7 μ, and was highly active in primary AML blasts with a median IC50 of 8.9 μ (range 5.7-37.2). Importantly, higher IC50 values were seen in normal hematopoietic cells. In AML and ALL, PFT-μ induced apoptosis and cell cycle arrest in a dose-dependent fashion. PFT-μ also led to an increase of the active form of caspase-3 and reduced the intracellular concentrations of AKT and ERK1/2 in NALM-6 cells. Moreover, PFT-μ enhanced cytotoxicity of cytarabine, 17-(allylamino)-17-desmethoxygeldanamycin, suberoylanilide hydroxamic acid, and sorafenib in NALM-6, TOM-1 and KG-1a cells. This is the first study demonstrating significant antileukemic effects of the HSP70 inhibitor PFT-μ, alone and in combination with different antineoplastic drugs in both AML and ALL. Our results suggest a potential therapeutic role for PFT-μ in acute leukemias. PMID:22829184

  17. Antileukemic activity of the HSP70 inhibitor pifithrin-μ in acute leukemia

    PubMed Central

    Kaiser, M; Kühnl, A; Reins, J; Fischer, S; Ortiz-Tanchez, J; Schlee, C; Mochmann, L H; Heesch, S; Benlasfer, O; Hofmann, W-K; Thiel, E; Baldus, C D

    2011-01-01

    Heat shock protein (HSP) 70 is aberrantly expressed in different malignancies and has emerged as a promising new target for anticancer therapy. Here, we analyzed the in vitro antileukemic effects of pifithrin-μ (PFT-μ), an inhibitor of inducible HSP70, in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) cell lines, as well as in primary AML blasts. PFT-μ significantly inhibited cell viability at low micromolar concentrations in all cell lines tested, with IC50 values ranging from 2.5 to 12.7 μ, and was highly active in primary AML blasts with a median IC50 of 8.9 μ (range 5.7–37.2). Importantly, higher IC50 values were seen in normal hematopoietic cells. In AML and ALL, PFT-μ induced apoptosis and cell cycle arrest in a dose-dependent fashion. PFT-μ also led to an increase of the active form of caspase-3 and reduced the intracellular concentrations of AKT and ERK1/2 in NALM-6 cells. Moreover, PFT-μ enhanced cytotoxicity of cytarabine, 17-(allylamino)-17-desmethoxygeldanamycin, suberoylanilide hydroxamic acid, and sorafenib in NALM-6, TOM-1 and KG-1a cells. This is the first study demonstrating significant antileukemic effects of the HSP70 inhibitor PFT-μ, alone and in combination with different antineoplastic drugs in both AML and ALL. Our results suggest a potential therapeutic role for PFT-μ in acute leukemias. PMID:22829184

  18. Antioxidant and photoprotective activity of a lipophilic extract containing neolignans from Krameria triandra roots.

    PubMed

    Carini, Marina; Aldini, Giancarlo; Orioli, Marica; Facino, Roberto Maffei

    2002-03-01

    The antioxidant/photoprotective potential of a standardized Krameria triandra (KT) root extract (15% neolignans) has been evaluated in different cell models, rat erythrocytes and human keratinocytes cell lines, exposed to chemical (cumene hydroperoxide, CuOOH) and physical (UVB radiation) free radical inducers. The extract was significantly more active (IC50 0.28 +/- 0.04 microg/ml) than the typical chain-breaking antioxidant alpha-tocopherol (IC50 = 6.37 +/- 0.41 microg/ml) in inhibiting the CuOOH-induced hemolysis in rat blood cells. The KT constituent 2-(2,4-dihydroxyphenyl)-5-(E)-propenylbenzofuran, was the most active (IC50 = 0.03 +/- 0.005 microg/ml), followed by eupomatenoid 6 (IC50 = 0.29 +/- 0.06 microg/ml) and conocarpan (IC50 = 0.77 +/- 0.08 microg/ml). The same order of potency was observed in red blood cells exposed to UVB irradiation in continuo, with IC50 values 0.78 +/- 0.08 microg/ml for KT extract, 0.18 +/- 0.02 microg/ml for 2-(2,4-dihydroxyphenyl)-5-(E)-propenylbenzofuran, 0.95 +/- 0.11 microg/ml for eupomatenoid 6, and 3.8 +/- 0.39 microg/ml for conocarpan. In cultured human keratinocytes exposed to UVB radiation (50 mJ/cm2), KT extract (2.5-20 microg/ml) significantly and dose-dependently restrained the loss in cell viability and the intracellular oxidative damage: glutathione (GSH) depletion and the rise in dichlorofluorescein (DCF), marker of peroxide accumulation, were suppressed by 20 microg/ml KT and in parallel cell morphology maintained. The cytoprotective effect of the extract was confirmed in a more severe model of cell damage: exposure of keratinocytes to higher UVB doses (300 mJ/cm2), which induce a 50% cell death. In keratinocyte cultures supplemented with 10 microg/ml, cell viability was almost completely preserved and more efficiently than with (-)-epigallocatechin 3-gallate and green tea. The results of this study indicate the potential use of Rhatany extracts, standardized in neolignans, as topical antioxidants

  19. DNA-binding affinity and anticancer activity of β-carboline-chalcone conjugates as potential DNA intercalators: Molecular modelling and synthesis.

    PubMed

    Shankaraiah, Nagula; Siraj, K P; Nekkanti, Shalini; Srinivasulu, Vunnam; Sharma, Pankaj; Senwar, Kishna Ram; Sathish, Manda; Vishnuvardhan, M V P S; Ramakrishna, Sistla; Jadala, Chetna; Nagesh, Narayana; Kamal, Ahmed

    2015-04-01

    A new series of DNA-interactive β-carboline-chalcone conjugates have been synthesized and evaluated for their in vitro cytotoxicity and DNA-binding affinity. It has been observed that most of these new hybrids have shown potent cytotoxic activities on A-549 (lung adenocarcinoma) cell lines with IC50 values lower than 10 μM. The hybrid 7b is more effective against some of the selected cancer cell lines with IC50 values less than 50 μM. In addition, compounds 7e, 7k, 7p-u has displayed significant elevation in ΔTm of DNA in comparison to Adriamycin, suggesting significant interaction and remarkable DNA stabilization. The DNA intercalation of these new hybrids has been investigated by fluorescence titration, DNA viscosity measurements, molecular docking as well as molecular dynamics and the results are in agreement with the thermal denaturation studies. PMID:25771335

  20. Increase of anti-HIV activity of C-peptide fusion inhibitors using a bivalent drug design approach.

    PubMed

    Ling, Yanbo; Xue, Huifang; Jiang, Xifeng; Cai, Lifeng; Liu, Keliang

    2013-09-01

    We reported the design of fusion inhibitors with improved activity using a multivalent inhibitor design strategy. First, we chose C29 as the template sequence, which is a 29-mer peptide derived from HIV-1 gp41 CHR domain and has anti-HIV activity of IC50 118 nM in a cell-cell fusion assay. We optimized the crosslink sites and linkers of the template peptide. We found that N-terminal crosslink caused activity improvement based on the multivalent co-operative effect. Especially, the IC50 of peptide (CAcaC29)2 was improved from 49.02 (monomeric form) to 5.71 nM. Compared with long peptides, short peptides may be more suitable to analyze the co-operative effect. So we selected a shorter peptide C22 to synthesize the bivalent inhibitors. Due its weak helicity, no co-operative effect appeared. Therefore, we chose SC22EK, which were introduced salt bridges to consolidate the helicity based on the natural sequence C22. The cross-linked (CAcaSC22EK)2 was four times more potent than the monomer SC22EK in anti-HIV activity, with an IC50 value of 4.92 nM close to the high active peptide fusion inhibitor C34. The strategy used in this study may be used to design new fusion inhibitors to interfere similar processes. PMID:23906421

  1. 3,4,5-Trisubstituted Furan-2(5H)-one Derivatives: Efficient one-pot Synthesis and Evaluation of Cytotoxic Activity.

    PubMed

    Basyouni, W M; El-Bayouki, Kh A M; El-Sayed, A S; Tohamy, W M; Farag, M M S; Abd-El-Baseer, M A

    2015-09-01

    A series of 3,4,5-trisubstituted 2(5H)-furanone derivatives was synthesized through one-pot reaction of amines, aldehydes and diethyl acetylenedicarboxylate. Silica sulfuric acid efficiently catalyzes the 3-component reaction to afford the corresponding 2(5H)-furanones in high yields. The synthesized compounds were tested against HEPG2, MCF7 and CACO tumor cell lines. The cytotoxic activity for the tested compounds showed that: ethyl 2-(4-fluorophenyl)-5-oxo-4-(phenylamino)-2,5-dihydrofuran-3-carboxylate exhibited significant antitumor activity against HEPG2 and MCF7 cell lines (IC50 values 0.002 and 0.002 µM, respectively) more than reference drug (IC50 0.007, 0.005 µM). PMID:25207706

  2. Synthesis and Cytotoxic Activity of Biphenylurea Derivatives Containing Indolin-2-one Moieties.

    PubMed

    Eldehna, Wagdy M; Fares, Mohamed; Ibrahim, Hany S; Alsherbiny, Muhammad A; Aly, Mohamed H; Ghabbour, Hazem A; Abdel-Aziz, Hatem A

    2016-01-01

    In our endeavor towards the development of potent anticancer agents, two different sets of biphenylurea-indolinone conjugates, 5a-s and 8a,b were synthesized. The in vitro cytotoxicity of the synthesized compounds was examined in two human cancer cell lines, namely MCF-7 breast cancer and PC-3 prostate cancer cells using the sulforhodamine B (SRB) colorimetric assay. In particular, the MCF-7 cancer cell line was more susceptible to the synthesized compounds. Compound 5o (IC50 = 1.04 ± 0.10 μM) emerged as the most active member in this study against MCF-7, with 7-fold increased activity compared to the reference drug, doxorubicin (IC50 = 7.30 ± 0.84 μM). Compounds 5l, 5q and 8b also exhibited superior cytotoxic activity against MCF-7 with IC50 values of 1.93 ± 0.17, 3.87 ± 0.31 and 4.66 ± 0.42 μM, respectively. All of the tested compounds were filtered according to the Lipinski and Veber rules and all of them passed the filters. Additionally, several ADME descriptors for the synthesized compounds 5a-s and 8a,b were predicted via a theoretical kinetic study performed using the Discovery Studio 2.5 software. PMID:27294903

  3. Design, Synthesis and Evaluation of Antiproliferative Activity of New Benzimidazolehydrazones.

    PubMed

    Onnis, Valentina; Demurtas, Monica; Deplano, Alessandro; Balboni, Gianfranco; Baldisserotto, Anna; Manfredini, Stefano; Pacifico, Salvatore; Liekens, Sandra; Balzarini, Jan

    2016-01-01

    The synthesis and antiproliferative activity of new benzimidazole derivatives bearing an hydrazone mojety at the 2-position is described. The new N'-(4-arylidene)-1H-benzo[d]imidazole-2-carbohydrazides were evaluated for their cytostatic activity toward the murine leukemia (L1210), human T-cell leukemia (CEM), human cervix carcinoma (HeLa) and human pancreas carcinoma cells (Mia Paca-2). A preliminary structure-activity relationship could be defined. Some of the compounds possess encouraging and consistent antiproliferative activity, having IC50 values in the low micromolar range. PMID:27144551

  4. Pharmacological actions of Y-24180, a new specific antagonist of platelet activating factor (PAF): II. Interactions with PAF and benzodiazepine receptors.

    PubMed

    Takehara, S; Mikashima, H; Muramoto, Y; Terasawa, M; Setoguchi, M; Tahara, T

    1990-12-01

    The inhibitory effect of Y-24180, 4-(2-chlorophenyl)-2-[2-(4-isobutylphenyl)ethyl]-6,9-dimethyl-6H-t hieno [3,2-f][1,2,4]triazolo [4,3-a][1,4]diazepine, on platelet activating factor (PAF)-induced platelet aggregation and the specific binding of 3H-PAF to platelets was compared with other thienodiazepine derivatives, WEB 2086 and etizolam. Y-24180 inhibited PAF-induced rabbit platelet aggregation in vitro (IC50 3.84 nM), but had little effect on adenosine diphosphate- or arachidonic acid-induced aggregation. WEB 2086 and etizolam also showed an inhibitory effect of PAF-induced aggregation (IC50 values are 456 and 6730 nM, respectively). In PAF-induced human platelet aggregation, Y-24180 (IC50 0.84 nM) was more potent than WEB 2086 (IC50 4.21 nM) and etizolam (IC50 998 nM). Y-24180, WEB 2086 and etizolam displaced 3H-PAF binding from the washed-platelets of rabbits with an IC50 value of 3.50, 9.35 and 29.5 nM, respectively. In rabbits, pretreatment with Y-24180 and WEB 2086 antagonized PAF-induced platelet aggregation dose-dependently. The significant inhibitory effect of Y-24180 (1 mg/kg, p.o.) lasted 72 hr after a single dose oral administration. WEB 2086 (10 mg/kg, p.o.) also antagonized the ex vivo response induced by PAF 1 hr after administration, but no significant effect was observed 3 hr after administration. Y-24180 displaced 3H-diazepam binding from the synaptosomal membranes of rat cerebral cortex with a Ki value of 3.68 microM. The affinity of Y-24180 for benzodiazepine(BZP) receptors was lower than those of WEB 2086 and etizolam and was about 1000 times lower than that for PAF receptors in platelets. PMID:1965554

  5. A Fundamental Relationship Between Hydrophobic Properties and Biological Activity for the Duocarmycin Class of DNA Alkylating Antitumor Drugs: Hydrophobic Binding-Driven-Bonding

    PubMed Central

    Wolfe, Amanda L.; Duncan, Katharine K.; Lajiness, James P.; Zhu, Kaicheng; Duerfeldt, Adam S.; Boger, Dale L.

    2013-01-01

    Two systematic series of increasingly hydrophilic derivatives of duocarmycin SA are described that feature the incorporation of ethylene glycol units (n = 1–5) into the methoxy substituents of the trimethoxyindole subunit. These derivatives exhibit progressively increasing water solubility, along with progressive decreases in cell growth inhibitory activity and DNA alkylation efficiency with the incremental ethylene glycol unit incorporations. A linear relationship between cLogP and –logIC50 for cell growth inhibition and –logAE (AE = cell free DNA alkylation efficiency) is observed where cLogP values span the productive range of 2.5–0.49 and –logIC50 values span the range of 11.2–6.4, representing IC50 values covering a 105 range (0.008 to 370 nM). The results quantify a fundamental role the compound hydrophobic character plays in the expression of the biological activity of members in this class, driving the intrinsically reversible DNA alkylation reaction, and define the stunning magnitude of its effect. PMID:23944748

  6. In vitro antimalarial activity and chloroquine potentiating action of two bisbenzylisoquinoline enantiomer alkaloids isolated from Strychnopsis thouarsii and Spirospermum penduliflorum.

    PubMed

    Ratsimamanga-Urverg, S; Rasoanaivo, P; Ramiaramanana, L; Milijaona, R; Rafatro, H; Verdier, F; Rakoto-Ratsimamanga, A; Le Bras, J

    1992-12-01

    The bisbenzylisoquinolines 7-O-demethyltetrandrine and limacine, respectively, isolated from Strychnopsis thouarsii Baill. and Spirospermum penduliflorum Thou. were evaluated for their intrinsic antimalarial activity in vitro and chloroquine potentiating action against the chloroquine-resistant Plasmodium falciparum FCM 29 originating from Cameroon. They both showed significant antiplasmodial potency in vitro with very similar IC50 values of respectively, 740 nM and 789 nM (IC50 = 214 nM for chloroquine used as standard drug), which demonstrated that the stereochemistry of the C-1 and C-1' configuration likely plays a role in the chloroquine potentiating effect of these drugs. If confirmed in vivo, these results may account for the traditional use of the two plants as antimalarials and adjuvant to chloroquine in Madagascan folklore remedies. PMID:1484894

  7. Synthesis and cytotoxic activity of N-((2-methyl-4(3H)-quinazolinon-6-yl)methyl)dithiocarbamates.

    PubMed

    Cao, Sheng-Li; Wang, Yao; Zhu, Lin; Liao, Ji; Guo, Yan-Wen; Chen, Lin-Lin; Liu, Hong-Qin; Xu, Xingzhi

    2010-09-01

    A series of N-((2-methyl-4(3H)-quinazolinon-6-yl)methyl)dithiocarbamates 5a-w were synthesized and evaluated for their cytotoxic activity against five human cancer cell lines. We found that compound 5k inhibited proliferation of A549, MCF-7, HeLa, HT29 and HCT-116 cells with IC(50) values of 5.44, 7.15, 12.16, 10.35 and 11.44 microM, respectively. Compound 5i was the most potent with an IC(50) value of 3.65 microM against proliferation of MCF-7 cells, while 5n was the most potent with an IC(50) value of 5.09 microM against proliferation of A549 cells. Cell cycle analysis showed that both 5i and 5k arrested A549 cells at S and G2/M phases, suggesting that these compounds act through mechanisms different from 5-fluorouracil, which arrests cells at S phase only. PMID:20538385

  8. Phytochemical constituents, nutritional values, phenolics, flavonols, flavonoids, antioxidant and cytotoxicity studies on Phaleria macrocarpa (Scheff.) Boerl fruits

    PubMed Central

    2014-01-01

    Background The edible fruits of Phaleria macrocarpa (Scheff.) Boerl are widely used in traditional medicine in Indonesia. It is used to treat a variety of medical conditions such as - cancer, diabetes mellitus, allergies, liver and heart diseases, kidney failure, blood diseases, high blood pressure, stroke, various skin diseases, itching, aches, and flu. Therefore, it is of great interest to determine the biochemical and cytotoxic properties of the fruit extracts. Methods The methanol, hexane, chloroform, ethyl acetate, and water extracts of P. macrocarpa fruits were examined for phytochemicals, physicochemicals, flavonols, flavonoids and phenol content. Its nutritional value (A.O.A.C method), antioxidant properties (DPPH assay) and cytotoxicity (MTT cell proliferation assay) were also determined. Results A preliminary phyotochemical screening of the different crude extracts from the fruits of P. macrocarpa showed the presence secondary metabolites such as of flavonoids, phenols, saponin glycosides and tannins. The ethyl acetate and methanol extracts displayed high antioxidant acitivity (IC50 value of 8.15±0.02 ug/mL) in the DPPH assay comparable to that of the standard gallic acid (IC50 value of 10.8±0.02 ug/mL). Evaluation of cytotoxic activity showed that the crude methanol extract possessed excellent anti-proliferative activity against SKOV-3 (IC50 7.75±2.56 μg/mL) after 72 hours of treatment whilst the hexane and ethyl acetate extracts displayed good cytotoxic effect against both SKOV-3 and MDA-MB231 cell lines. The chloroform extract however, showed selective inhibitory activity in the breast cancer cell line MDA-MB231 (IC50 7.80±1.57 μg/mL) after 48 hours of treatment. There was no cytotoxic effect observed in the Ca Ski cell line and the two normal cell lines (MRC-5 and WRL-68). Conclusion The methanol extract and the ethyl acetate fraction of P. macrocarpa fruits exhibited good nutritional values, good antioxidant and cytotoxic activities, and merits

  9. High throughput and rapid screening of marine protein hydrolysates enriched in peptides with angiotensin-I-converting enzyme inhibitory activity by capillary electrophoresis.

    PubMed

    He, Hai-Lun; Chen, Xiu-Lan; Wu, Hao; Sun, Cai-Yun; Zhang, Yu-Zhong; Zhou, Bai-Cheng

    2007-12-01

    Twelve kinds of marine protein materials, including fish, shrimp, seashell, algae and seafood wastes were selected for the hydrolysis using four different proteases. The IC(50) values for angiotensin-converting enzyme (ACE) inhibitory activity of 48 hydrolysates were rapidly determined by capillary electrophoresis (CE). The values ranged from 0.17 to 501.7mg/ml, and were affected by both the marine protein resources and the selected proteases. Hydrolysates of the lowest IC(50) values were from shrimp (Acetes chinensis), shark meat, mackerel bone, Polysiphonia urceolata and Spirulina platensis, indicating these five kinds of marine food proteins contained beneficial materials for the production of ACE inhibitory peptides by proteolysis. The hydrolysates obtained using proteases Protamex and SM98011 had lower IC(50) values, showing these two proteases were superior to others. The CE method achieved the same sensitivity as the high performance liquid chromatography (HPLC) method. However, the CE method was faster and, as a result, more economical. Therefore, CE had potential for rapid screening of marine protein hydrolysates enriched in ACE inhibitory peptides. PMID:17317156

  10. Antiviral activity of four types of bioflavonoid against dengue virus type-2

    PubMed Central

    2011-01-01

    Background Dengue is a major mosquito-borne disease currently with no effective antiviral or vaccine available. Effort to find antivirals for it has focused on bioflavonoids, a plant-derived polyphenolic compounds with many potential health benefits. In the present study, antiviral activity of four types of bioflavonoid against dengue virus type -2 (DENV-2) in Vero cell was evaluated. Anti-dengue activity of these compounds was determined at different stages of DENV-2 infection and replication cycle. DENV replication was measured by Foci Forming Unit Reduction Assay (FFURA) and quantitative RT-PCR. Selectivity Index value (SI) was determined as the ratio of cytotoxic concentration 50 (CC50) to inhibitory concentration 50 (IC50) for each compound. Results The half maximal inhibitory concentration (IC50) of quercetin against dengue virus was 35.7 μg mL-1 when it was used after virus adsorption to the cells. The IC50 decreased to 28.9 μg mL-1 when the cells were treated continuously for 5 h before virus infection and up to 4 days post-infection. The SI values for quercetin were 7.07 and 8.74 μg mL-1, respectively, the highest compared to all bioflavonoids studied. Naringin only exhibited anti-adsorption effects against DENV-2 with IC50 = 168.2 μg mL-1 and its related SI was 1.3. Daidzein showed a weak anti-dengue activity with IC50 = 142.6 μg mL-1 when the DENV-2 infected cells were treated after virus adsorption. The SI value for this compound was 1.03. Hesperetin did not exhibit any antiviral activity against DENV-2. The findings obtained from Foci Forming Unit Reduction Assay (FFURA) were corroborated by findings of the qRT-PCR assays. Quercetin and daidzein (50 μg mL-1) reduced DENV-2 RNA levels by 67% and 25%, respectively. There was no significant inhibition of DENV-2 RNA levels with naringin and hesperetin. Conclusion Results from the study suggest that only quercetin demonstrated significant anti-DENV-2 inhibitory activities. Other bioflavonoids

  11. Synthesis and Structure–Activity Relationship Studies of Derivatives of the Dual Aromatase–Sulfatase Inhibitor 4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate

    PubMed Central

    Woo, L W Lawrence; Wood, Paul M; Bubert, Christian; Thomas, Mark P; Purohit, Atul; Potter, Barry V L

    2013-01-01

    4-{[(4-Cyanophenyl)(4H-1,2,4-triazol-4-yl)amino]methyl}phenyl sulfamate and its ortho-halogenated (F, Cl, Br) derivatives are first-generation dual aromatase and sulfatase inhibitors (DASIs). Structure–activity relationship studies were performed on these compounds, and various modifications were made to their structures involving relocation of the halogen atom, introduction of more halogen atoms, replacement of the halogen with another group, replacement of the methylene linker with a difluoromethylene linker, replacement of the para-cyanophenyl ring with other ring structures, and replacement of the triazolyl group with an imidazolyl group. The most potent in vitro DASI discovered is an imidazole derivative with IC50 values against aromatase and steroid sulfatase in a JEG-3 cell preparation of 0.2 and 2.5 nm, respectively. The parent phenol of this compound inhibits aromatase with an IC50 value of 0.028 nm in the same assay. PMID:23495205

  12. Antioxidant activities and phenolics of Passiflora edulis seed recovered from juice production residue.

    PubMed

    Lourith, Nattaya; Kanlayavattanakul, Mayuree

    2013-01-01

    Passion fruit seed was refluxed in methanolic water and further liquid - liquid extracted yielding n-Hexane, Ethyl acetate (EtOAc) and aqueous (Aq.) extracts. The EtOAc part was the most potent antioxidant (IC 50DPPH = 2.7 ± 0.2 and IC 50ABTS = 9.0 ± 0.0 µg/mL) that significantly (p < 0.05) better than Aq. extract (IC 50DPPH = 177.8 ± 1.3 and IC 50ABTS = 15.4 ± 0.0 µg/mL). The antioxidant EtOAc exhibited ferric reducing powder (EC1mM FeSO4 = 2,813.9 ± 11.6) and tyrosinase inhibitory effect (39.9 ± 0.0 % at 1 mg/mL). The more potent active extract had significant higher total phenolic content than the Aq. one (p < 0.05). Sun protection factor of the EtOAc extract was comparable to ferulic acid. Chlorogenic acid, rosmarinic acid and quercetin were highly found in EtOAc extract, whereas kojic acid and gallic acid were largely determined in the Aq. part. The most potent biologically active fraction was non cytotoxic in vero cells at the highest test concentration (50 µg/mL). A process to minimize the waste from the fruit juice production is offered. Passion fruit value and profitability in agribusinesses will be increased by the biochemical transformation of the seed into active extracts appraisal for natural cosmetic as a multifunction ingredient. PMID:23535311

  13. Chemical composition of the essential oils of variegated pink-fleshed lemon (Citrus x limon L. Burm. f.) and their anti-inflammatory and antimicrobial activities.

    PubMed

    Hamdan, Dalia; Ashour, Mohamed L; Mulyaningsih, Sri; El-Shazly, Assem; Wink, Michael

    2013-01-01

    The volatile secondary metabolites of essential oils from fruit peel and leaves of variegated pink-fleshed lemon (Citrus x limon) were investigated using GLC and GLC-MS (gas-liquid chromatography-mass spectroscopy). Altogether 141 compounds were identified and quantified, accounting for 99.59% and 96.33% of the total hydrodistilled peel and leaf oil, respectively. Limonene occurred in higher amounts in fruit peel (52.73%) than in leaf oil (29.13%). Neral (12.72%), neryl acetate (8.53%), p-menth-1-en-7-al (4.63%), beta-pinene (6.35%), and nerol (4.42%) were the most abundant constituents in leaf oil, whereas gamma-terpinene (9.88%), beta-pinene (7.67%), geranial (4.44%), and neral (3.64%) dominated in the fruit peel oil. The antioxidant, anti-inflammatory, antitrypanosomal, and antimicrobial activities of the fruit peel essential oil were evaluated. The oil had a low antioxidant activity with an IC50 value of (26.66 +/- 2.07) mg/ml as compared to the efficient antioxidant ascorbic acid [IC50 (16.32 +/- 0.16) microg/ml]. The oil moderately inhibited soybean 5-lipoxygenase (5-LOX) with an IC50 value of (32.05 +/- 3.91) microg/ml and had moderate antitrypanosomal activity [IC50 (60.90 +/- 0.91) microg/ml]. In addition, moderate antimicrobial activities were detected against Gram-positive bacteria (Bacillus subtilis, Staphylococcus capitis, Micrococcus luteus), one Gram-negative bacterium (Pseudomonas fluorescens), and yeasts (Saccharomyces cerevisiae, Candida parapsilosis). PMID:24066512

  14. Purification of Flavonoids from Chinese Bayberry (Morella rubra Sieb. et Zucc.) Fruit Extracts and α-Glucosidase Inhibitory Activities of Different Fractionations.

    PubMed

    Yan, Shuxia; Zhang, Xianan; Wen, Xin; Lv, Qiang; Xu, Changjie; Sun, Chongde; Li, Xian

    2016-01-01

    Chinese bayberry (Morella rubra Sieb. et Zucc.) fruit have a diverse flavonoid composition responsible for the various medicinal activities, including anti-diabetes. In the present study, efficient simultaneous purification of four flavonoid glycosides, i.e., cyanidin-3-O-glucoside (1), myricetin-3-O-rhamnoside (2), quercetin-3-O-galactoside (3), quercetin-3-O-rhamnoside (4), from Chinese bayberry pulp was established by the combination of solid phase extract (SPE) by C18 Sep-Pak(®) cartridge column chromatography and semi-preparative HPLC (Prep-HPLC), which was followed by HPLC and LC-MS identification. The purified flavonoid glycosides, as well as different fractions of fruit extracts of six bayberry cultivars, were investigated for α-glucosidase inhibitory activities. The flavonol extracts (50% methanol elution fraction) of six cultivars showed strong α-glucosidase inhibitory activities (IC50 = 15.4-69.5 μg/mL), which were higher than that of positive control acarbose (IC50 = 383.2 μg/mL). Four purified compounds 1-4 exerted α-glucosidase inhibitory activities, with IC50 values of 1444.3 μg/mL, 418.8 μg/mL, 556.4 μg/mL, and 491.8 μg/mL, respectively. Such results may provide important evidence for the potential anti-diabetic activity of different cultivars of Chinese bayberry fruit and the possible bioactive compounds involved. PMID:27589714

  15. Synthesis and β-glucuronidase inhibitory activity of 2-arylquinazolin-4(3H)-ones.

    PubMed

    Khan, Khalid Mohammed; Saad, Syed Muhammad; Shaikh, Nimra Naveed; Hussain, Shafqat; Fakhri, Muhammad Imran; Perveen, Shahnaz; Taha, Muhammad; Choudhary, Muhammad Iqbal

    2014-07-01

    2-Arylquinazolin-4(3H)-ones 1-25 were synthesized by reacting anthranilamide with various benzaldehydes using CuCl2·2H2O as a catalyst in ethanol under reflux. Synthetic 2-arylquinazolin-4(3H)-ones 1-25 were evaluated for their β-glucuronidase inhibitory potential. A trend of inhibition IC50 against the enzyme in the range of 0.6-198.2μM, was observed and compared with the standard d-saccharic acid 1,4-lactone (IC50=45.75±2.16μM). Compounds 13, 19, 4, 12, 14, 22, 23, 25, 15, 8, 17, 11, 21, 1, 3, 18, 9, 2, and 24 with the IC50 values within the range of 0.6-44.0μM, indicated that the compounds have superior activity than the standard. The compounds showed no cytotoxic effects against PC-3 cells. A structure-activity relationship is established. PMID:24844756

  16. Gossypol enantiomers potently inhibit human placental 3β-hydroxysteroid dehydrogenase 1 and aromatase activities.

    PubMed

    Dong, Yaoyao; Mao, Baiping; Li, Linxi; Guan, Hongguo; Su, Ying; Li, Xiaoheng; Lian, Qingquan; Huang, Ping; Ge, Ren-Shan

    2016-03-01

    Gossypol is a chemical isolated from cotton seeds. It exists as (+) or (-) enantiomer and has been tested for anticancer, abortion-inducing, and male contraception. Progesterone formed from pregnenolone by 3β-hydroxysteroid dehydrogenase 1 (HSD3B1) and estradiol from androgen by aromatase (CYP19A1) are critical for the maintenance of pregnancy or associated with some cancers. In this study we compared the potencies of (+)- and (-)-gossypol enantiomers in the inhibition of HSD3B1 and aromatase activities as well as progesterone and estradiol production in human placental JEG-3 cells. (+) Gossypol showed potent inhibition on human placental HSD3B1 with IC50 value of 2.3 μM, while (-) gossypol weakly inhibited it with IC50 over 100 μM. In contrast, (-) gossypol moderately inhibited CYP19A1 activity with IC50 of 23 μM, while (+) gossypol had no inhibition when the highest concentration (100 μM) was tested. (+) Gossypol enantiomer competitively inhibited HSD3B1 against substrate pregnenolone and showed mixed mode against NAD(+). (-) Gossypol competitively inhibited CYP19A1 against substrate testosterone. Gossypol enantiomers showed different potency related to their inhibition on human HSD3B1 and CYP19A1. Whether gossypol enantiomer is used alone or in combination relies on its application and beneficial effects. PMID:26709042

  17. In vitro studies on α-glucosidase inhibition, antioxidant and free radical scavenging activities of Hedyotis biflora L.

    PubMed

    Nimal Christhudas, I V S; Praveen Kumar, P; Sunil, Christudas; Vajravijayan, S; Lakshmi Sundaram, R; Jenifer Siril, S; Agastian, P

    2013-06-01

    Aim of this study was to evaluate the in vitro α-glucosidase inhibition and antioxidant activity of hexane, ethyl acetate and methanol extracts of Hedyotis biflora L. (Rubiaceae). In in vitro α-glucosidase inhibition and antioxidant activity, the methanol extract showed potent effect compared to hexane and ethyl acetate extracts. The methanol extract of H. biflora (HBMe) showed 50% α-glucosidase inhibition at the concentration of 480.20 ± 2.37 μg/ml. The total phenolic content of HBMe was 206.81 ± 1.11 mg of catechol equivalents/g extract. HBMe showed great scavenging activity on 2,2-diphenyl-picrylhydrazyl (DPPH) (IC(50) 520.21 ± 1.02 μg/ml), hydroxyl (IC(50) 510.21 ± 1.51 μg/ml), nitric oxide (IC(50) 690.20 ± 2.13 μg/ml) and superoxide (IC(50) 510.31 ± 1.45 μg/ml) radicals, as well as high reducing power. HBMe also showed a strong suppressive effect on lipid peroxidation. Using the β-carotene method, the scavenging values of HBMe was significantly lower than BHT, and metal chelating ability of HBMe also showed a strong inhibition effect when compared to the reference standard. The active compound ursolic acid from HBMe was identified using various spectroscopical studies. The results obtained in this study clearly indicate that HBMe has a significant potential to use as a natural α-glucosidase inhibition, antioxidant agent. PMID:23411299

  18. Evaluation of phytochemical content, nutritional value and antioxidant activity of Phanji - Rivea hypocrateriformis (Desr.) Choisy leaf

    PubMed Central

    Borkar, Sneha D.; Naik, Raghavendra; Shukla, Vinay J.; Acharya, Rabinarayan

    2015-01-01

    Background: Rivea hypocrateriformis (Desr.) Choisy is known to be the source plant of Phanji, a classically delineated leafy vegetable which is till date used by some hill dwelling Kandha tribes of Odisha. Though it is in use since a long time, it is not yet evaluated for its nutritive value. Aim: The leaves of R. hypocrateriformis were evaluated for its nutritive value and antioxidant potential. Materials and Methods: The in vitro antioxidant properties of the leaf of R. hypocrateriformis were screened through 1,1-diphenyl-2-picrylhydrazyl (DPPH) and total antioxidant capacity. Phytochemicals, crude protein, fat, carbohydrate, energy value, and mineral content of the leaves of the plant were evaluated with standard procedures. Results: In phytochemical analysis, tannin, alkaloids, flavonoids, and carbohydrates were present in leaf powder of R. hypocrateriformis. Energy content was found to be highest (331.54 kcals/100 g). Carbohydrate, fat, protein, calcium, magnesium, phosphorous, and zinc were present in 57.63%, 2.66%, 19.27%, 0.99%, 0.34%, 0.32%, and 0.011%, respectively. The IC50 values of the extract and ascorbic acid were found to be 254 ± 5.29 μg/ml and 11.67 ± 0.58 μg/ml, respectively. Percentage scavenging of DPPH radical was found to rise with increasing concentration of the crude extract. Total antioxidant capacity of the extract was found to be 111.30 ± 0.003 mcg. Conclusion: The results of this study indicate that the leaves of R. hypocrateriformis contain secondary metabolites such as tannin and possess mild antioxidant properties. Nutritional analysis indicates the presence of energy in highest amount, carbohydrates, proteins, fats, calcium, phosphorous, zinc, and magnesium. PMID:27313417

  19. A New Alkamide with an Endoperoxide Structure from Acmella ciliata (Asteraceae) and Its in Vitro Antiplasmodial Activity.

    PubMed

    Silveira, Narjara; Saar, Julia; Santos, Alan Diego C; Barison, Andersson; Sandjo, Louis P; Kaiser, Marcel; Schmidt, Thomas J; Biavatti, Maique W

    2016-01-01

    From the aerial parts of Acmella ciliata (H.B.K.) Cassini (basionym Spilanthes ciliata Kunth; Asteraceae), three alkamides were isolated and identified by mass- and NMR spectroscopic methods as (2E,6E,8E)-N-isobutyl-2,6,8-decatrienamide (spilanthol, (1)), N-(2-phenethyl)-2E-en-6,8-nonadiynamide (2) and (2E,7Z)-6,9-endoperoxy-N-isobutyl-2,7-decadienamide (3). While 1 and 2 are known alkamides, compound 3 has not been described until now. It was found that the unusual cyclic peroxide 3 exists as a racemate of both enantiomers of each alkamide; the 6,9-cis- as well as the 6,9-trans-configured diastereomers, the former represents the major, the latter the minor constituent of the mixture. In vitro tests for activity against the human pathogenic parasites Trypanosoma brucei rhodesiense and Plasmodium falciparum revealed that 1 and 3 possess activity against the NF54 strain of the latter (IC50 values of 4.5 and 5.1 µM, respectively) while 2 was almost inactive. Compound 3 was also tested against multiresistant P. falciparum K1 and was found to be even more active against this parasite strain (IC50 = 2.1 µM) with considerable selectivity (IC50 against L6 rat skeletal myoblasts = 168 µM). PMID:27294907

  20. Racemosin C, a novel minor bisindole alkaloid with protein tyrosine phosphatase-1B inhibitory activity from the green alga Caulerpa racemosa.

    PubMed

    Yang, Hui; Liu, Ding-Quan; Liang, Tong-Jun; Li, Jia; Liu, Ai-Hong; Yang, Peng; Lin, Kun; Yu, Xiao-Qing; Guo, Yue-Wei; Mao, Shui-Chun; Wang, Bin

    2014-12-01

    A novel minor bisindole alkaloid, racemosin C (1), characterized by a naturally unprecedented 8-hydroxy-2,4,6-cyclooctatrienone ring fused with two indole systems, was isolated from the green alga Caulerpa racemosa, together with one known related metabolite, caulersin (2). The structure of 1 was elucidated on the basis of extensive spectroscopic analysis, and by comparison with the data of related known compounds. A plausible biosynthetic pathway of 1 was proposed. Compounds 1 and 2 exhibited significant PTP1B inhibitory activity with IC50 values of 5.86 ± 0.57 and 7.14 ± 1.00 μM, respectively, compared with the positive control oleanolic acid (IC50 = 3.03 ± 0.20 μM). On the basis of the data obtained, the Caulerpa bisindole alkaloids may be considered as a new class of PTP1B inhibitors. PMID:25296343

  1. Bisphosphonate Inhibition of a Plasmodium Farnesyl Diphosphate Synthase and a General Method for Predicting Cell-Based Activity from Enzyme Data

    PubMed Central

    Mukkamala, Dushyant; No, Joo Hwan; Cass, Lauren M.; Chang, Ting-Kai; Oldfield, Eric

    2009-01-01

    We screened 26 bisphosphonates against a farnesyl diphosphate synthase from Plasmodium vivax, finding a poor correlation between enzyme and cell growth inhibition (R2 = 0.06). To better predict cell activity data, we then used a combinatorial descriptor search in which pIC50(cell) = a pIC50(enzyme) + bB + cC + d, where B and C are descriptors (such as SlogP), and a—d are coefficients. R2 increased from 0.01 to 0.74 (for a leave-two-out test set of 26 predictions). The method was then further validated using data for nine other systems, including bacterial, viral, and mammalian cell systems. On average, experimental/predicted cell pIC50 correlations increased from R2 = 0.28 (for an enzyme-only test set) to 0.70 (for enzyme plus two descriptor test set predictions), while predictions based on scrambled cell activity had no predictive value (R2 = 0.13). These results are of interest since they represent a general way to predict cell from enzyme inhibition data, with in three cases, R2 values increasing from ∼0.02 to 0.72. PMID:19053772

  2. Anti-inflammatory, free radical scavenging and alpha-glucosidase inhibitory activities of Hamelia patens and its chemical constituents.

    PubMed

    Jiménez-Suárez, Verónica; Nieto-Camacho, Antonio; Jiménez-Estrada, Manuel; Alvarado Sánchez, Brenda

    2016-09-01

    Context Hamelia patens Jacq. (Rubiaceae) is traditionally used to treat wounds, inflammation and diabetes. However, there is still a lack of scientific evidence to support these applications. Objective The objective of this study is to evaluate the anti-inflammatory, antioxidant and antidiabetic activities of Hamelia patens, and identify its bioactive compounds. Materials and methods Four extracts were obtained by maceration and liquid-liquid extraction: HEX, DCM-EtOAc, MeOH-EtOAc and MeOH-Aq. The anti-inflammatory effect was evaluated orally on rat paw carrageenan-induced oedema over 6 h (50, 200 and 500 mg/kg), and topically in mouse ear oedema induced by 12-tetradecanoylphorbol-13-acetate (TPA) after 4 h (0.5 and 1 mg/ear). We also evaluated myeloperoxidase levels in ear tissue, 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging ability, and in vitro α-glucosidase inhibition. The chemical compounds were separated by column chromatography and identified by spectroscopic analysis. Results We found that the oral administration of the HEX extract at 500 and 200 mg/kg significantly decreased the carrageenan-induced inflammation after 1 and 3 h, respectively. The MeOH-EtOAc extract significantly inhibited myeloperoxidase activity (83.5%), followed by the DCM-EtOAc extract (76%), β-sitosterol/stigmasterol (72.7%) and the HEX extract (55%), which significantly decreased oedema induced by TPA at both doses, giving a similar effect to indomethacin. We also found that the MeOH-EtOAc, MeOH-Aq and DCM-EtOAc extracts showed good DPPH scavenging activity (IC50 values of 18.6, 93.9 and 158.2 μg/mL, respectively). The HEX extract showed the lowest α-glucosidase inhibition (an IC50 value of 26.07 μg/mL), followed by the MeOH-EtOAc extract (an IC50 value of 30.18 μg/mL), β-sitosterol/stigmasterol (IC50 34.6 μg/mL) and compound A ((6E,10E,14E,18E)-2,6,10,14,18,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene, an IC50 value of 114.6 μg/mL), which were

  3. Antioxidant Activity of Water-soluble Polysaccharides from Brasenia schreberi

    PubMed Central

    Xiao, Huiwen; Cai, Xueru; Fan, Yijun; Luo, Aoxue

    2016-01-01

    Objective: In order to investigate the antioxidant activities of polysaccharides (BPL-1 and BPL-2), one of the most important functional constituents in Brasenia schreberi was isolated from the external mucilage of B. schreberi (BPL-1) and the plant in vivo (BPL-2). This paper examines the relationship between the content of sulfuric radicals and uronic acid in BPL and the antioxidant activity of BPL. Materials and Methods: The free radicals, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+) and 1,1-diphnyl-2-picrylhydrazyl (DPPH-), were used to determine the antioxidant activity of BPL. The Fourier-transform infrared spectroscopy of BPL-1 and BPL-2 revealed typical characteristics of polysaccharides. Results: The two sample types had different contents. This was proved by their different adsorption peak intensities. The IC50 values of BPL-1 (31.189 mg/ml) and BPL-2 (1.863 mg/ml) showed significant DPPH radical scavenging activity. Based on the quantification of ABTS radical scavenging, the IC50 value of BPL-1 (5.460 mg/ml) was higher than that of BPL-2 (0.239 mg/ml). Therefore, in terms of the reducing power, the IC50 value of BPL-1 was too high to determine, and the IC50 value of BPL-2 was found to be 50.557 mg/ml. Hence, the antioxidant activity and total reducing power were high, and they were greater in BPL-2 than in BPL-1. In addition, BPL-2 was found to have more sulfuric radicals and uronic acid than BPL-1. Conclusion: The contents of sulfuric radicals and uronic acid are significantly correlated to the antioxidant activity and reducing power of BPL; the more sulfuric radicals and uronic acid, the more antioxidant activity and reducing power BPL has. SUMMARY The water-soluble crude polysaccharides obtained from the external mucilage and the Brasenia schreberi plant in vivo were confirmed to have high contents of sulfuric radicals and uronic acidBoth BPL-1 and BPL-2 exhibited antioxidative activity and reducing power, and their antioxidative

  4. Antibacterial and Antibiofilm Activities of Makaluvamine Analogs

    PubMed Central

    Nijampatnam, Bhavitavya; Nadkarni, Dwayaja H.; Wu, Hui; Velu, Sadanandan E.

    2015-01-01

    Streptococcus mutans is a key etiological agent in the formation of dental caries. The major virulence factor is its ability to form biofilms. Inhibition of S. mutans biofilms offers therapeutic prospects for the treatment and the prevention of dental caries. In this study, 14 analogs of makaluvamine, a marine alkaloid, were evaluated for their antibacterial activity against S. mutans and for their ability to inhibit S. mutans biofilm formation. All analogs contained the tricyclic pyrroloiminoquinone core of makaluvamines. The structural variations of the analogs are on the amino substituents at the 7-position of the ring and the inclusion of a tosyl group on the pyrrole ring N of the makaluvamine core. The makaluvamine analogs displayed biofilm inhibition with IC50 values ranging from 0.4 μM to 88 μM. Further, the observed bactericidal activity of the majority of the analogs was found to be consistent with the anti-biofilm activity, leading to the conclusion that the anti-biofilm activity of these analogs stems from their ability to kill S. mutans. However, three of the most potent N-tosyl analogs showed biofilm IC50 values at least an order of magnitude lower than that of bactericidal activity, indicating that the biofilm activity of these analogs is more selective and perhaps independent of bactericidal activity. PMID:25767719

  5. Trypanocidal Activity of Smallanthus sonchifolius: Identification of Active Sesquiterpene Lactones by Bioassay-Guided Fractionation

    PubMed Central

    Frank, F. M.; Ulloa, J.; Cazorla, S. I.; Maravilla, G.; Malchiodi, E. L.; Grau, A.; Martino, V.; Catalán, C.; Muschietti, L. V.

    2013-01-01

    In order to find novel plant-derived biologically active compounds against Trypanosoma cruzi, we isolated, from the organic extract of Smallanthus sonchifolius, the sesquiterpene lactones enhydrin (1), uvedalin (2), and polymatin B (3) by bioassay-guided fractionation technique. These compounds showed a significant trypanocidal activity against the epimastigote forms of the parasite with IC50 values of 0.84 μM (1), 1.09 μM (2), and 4.90 μM (3). After a 24 h treatment with 10 μg/mL of enhydrin or uvedalin, parasites were not able to recover their replication rate. Compounds 1 and 2 showed IC50 values of 33.4 μM and 25.0 μM against T. cruzi trypomastigotes, while polymatin B was not active. When the three compounds were tested against the intracellular forms of T. cruzi, they were able to inhibit the amastigote replication with IC50 of 5.17 μM, 3.34 μM, and 9.02 μM for 1, 2, and 3, respectively. The cytotoxicity of the compounds was evaluated in Vero cells obtaining CC50 values of 46.5 μM (1), 46.8 μM (2), and 147.3 μM (3) and the selectivity index calculated. According to these results, enhydrin and uvedalin might have potentials as agents against Chagas disease and could serve as lead molecules to develop new drugs. PMID:23840260

  6. Anticomplement activity of organic solvent extracts from Korea local Amarantaceae spp.

    PubMed

    Jung, Seil; Lee, Jai-Heon; Lee, Young-Choon; Moon, Hyung-In

    2012-04-01

    The study evaluated the anticomplement activity from various solvent extracts of nine Amarantaceae plants (Achyranthes japonica (Miq.) Nakai, Amaranthus mangostanus L., Amaranthus retroflexus L., Amaranthus spinosus L., Celosia argentea var. spicata., Amaranthus lividus L., Celosia cristata L., Amaranthus viridis L., Gomphrena globosa L.) from South Korea on the classical pathway. We have evaluated various organic solvent extract from nine Amarantaceae plants with regard to its anticomplement activity on the classical pathway. Achyranthes japonica chloroform extracts showed inhibitory activity against complement system with 50% inhibitory concentrations (IC(50)) value of 73.1μg/ml. This is the first report of anticomplement activity from Amarantaceae plants. PMID:21736535

  7. 2,6,9-Trisubstituted purines as CRK3 kinase inhibitors with antileishmanial activity in vitro.

    PubMed

    Řezníčková, Eva; Popa, Alexandr; Gucký, Tomáš; Zatloukal, Marek; Havlíček, Libor; Bazgier, Václav; Berka, Karel; Jorda, Radek; Popa, Igor; Nasereddin, Abdelmajeed; Jaffe, Charles L; Kryštof, Vladimír; Strnad, Miroslav

    2015-06-01

    Here we describe the leishmanicidal activities of a library of 2,6,9-trisubstituted purines that were screened for interaction with Cdc2-related protein kinase 3 (CRK3) and subsequently for activity against parasitic Leishmania species. The most active compound inhibited recombinant CRK3 with an IC50 value of 162 nM and was active against Leishmania major and Leishmania donovani at low micromolar concentrations in vitro. Its mode of binding to CRK3 was investigated by molecular docking using a homology model. PMID:25937014

  8. Structure/antileishmanial activity relationship study of naphthoquinones and dependency of the mode of action on the substitution patterns.

    PubMed

    Ali, Ahmad; Assimopoulou, Andreana Nikolaos; Papageorgiou, Vassilios Peter; Kolodziej, Herbert

    2011-12-01

    A series of naphthoquinones was tested for activity against both extracellular promastigote and intracellular amastigote Leishmania major GFP in vitro. In parallel, the compounds were evaluated for cytotoxic effects against bone marrow-derived macrophages (BMM Φ) as a mammalian host cell control. Most of the compounds noticeably inhibited the growth of extracellular parasites (IC (50) 0.5 to 6 µM) and the intracellular survival of L. major GFP amastigotes (IC (50) 1 to 7 µM) when compared with the antileishmanial drug amphotericin B (IC (50) of 2.5 and 0.2 µM, respectively). In general, antiprotozoal activity and host cell cytotoxicity seemed to increase in parallel. Conspicuously, the cytotoxic effect was less pronounced on infected host cells when compared with that on noninfected cells. Concerning structure/activity relationships for the tested naphthoquinones, some interesting structural features emerged from this study. Introduction of a methyl or methoxyl group at C-2 of the parent 1,4-naphthoquinone slightly increased the antileishmanial activity against clinically relevant amastigotes, while the presence of a hydroxyl function in this position dramatically reduced the effectiveness. In contrast, hydroxylation at C-5 and dihydroxy substitution at C-5 and C-8 significantly enhanced the antiprotozoal activity. Similarly, the presence of a side chain hydroxyl group PERI to a carbonyl function as represented in the series of shikonin/alkannin derivatives increased the activity when compared with substituted analogs. Within the series of naphthoquinones tested, the dimeric mixture of vaforhizin and isovaforhizin showed the highest activity IN VITRO against the clinically relevant intracellular amastigote with an IC (50) of 1.1 µM. With IC (50) values mostly in the range of 1-3 µM, the shikonin/alkannin derivatives proved to be similarly considerably leishmanicidal. None of the compounds tested was capable to induce NO production known to play a

  9. High antiallergic activity of 5,6,4'-trihydroxy-7,8,3'-trimethoxyflavone and 5,6-dihydroxy-7,8,3',4'-tetramethoxyflavone from eau de cologne mint (Mentha×piperita citrata).

    PubMed

    Sato, Akihiko; Tamura, Hirotoshi

    2015-04-01

    The following compounds with higher antiallergic activities were isolated from eau de cologne mint leaves: 5,6,4'-trihydroxy-7,8-dimethoxyflavone (6), 5,6,4'-trihydroxy-7,8,3'-trimethoxyflavone (7), 5,6-dihydroxy-7,3',4'-trimethoxyflavone (8), 5,6-dihydroxy-7,8,3',4'-tetramethoxyflavone (9), and 5,6-dihydroxy-7,8,4'-trimethoxyflavone (10). The IC50 values of compounds 6-10 against RBL-2H3 cells were 6.7, 2.4, 5.6, 3.0, and 6.1μM. Compounds 7 and 9 (IC50 2.4μM and 3.0μM) had the highest antiallergic activities among the flavonoids previously reported. The amounts of 7, 9, and 10 isolated were fairly high, at 177.7mg/kg, 278.0mg/kg, and 179.7mg/kg in the mint, respectively. LD5 value (index of toxicity) and LD5/IC50 ratio of 7 and 9 indicate that the safety is greater than that of luteolin, a typical antiallergic substance. The extract containing powerful antiallergic flavones, 6-10 with higher hydrophobicity could be selectively separated from the extract containing luteolin and other flavonoid glycosides by partition with dichloromethane and water. Therefore, compounds 7 and 9 in mint, and the dichloromethane extract would be the most potent and preventive resources against type I allergy. PMID:25704366

  10. Antigiardial activity of glycoproteins and glycopeptides from Ziziphus honey.

    PubMed

    Mohammed, Seif Eldin A; Kabashi, Ahmed S; Koko, Waleed S; Azim, M Kamran

    2015-01-01

    Natural honey contains an array of glycoproteins, proteoglycans and glycopeptides. Size-exclusion chromatography fractionated Ziziphus honey proteins into five peaks with molecular masses in the range from 10 to >200 kDa. The fractionated proteins exhibited in vitro activities against Giardia lamblia with IC50 values ≤ 25 μg/mL. Results indicated that honey proteins were more active as antiprotozoal agents than metronidazole. This study indicated the potential of honey proteins and peptides as novel antigiardial agents. PMID:25587739

  11. Mono- and bis-thiazolium salts have potent antimalarial activity.

    PubMed

    Hamzé, Abdallah; Rubi, Eric; Arnal, Pascal; Boisbrun, Michel; Carcel, Carole; Salom-Roig, Xavier; Maynadier, Marjorie; Wein, Sharon; Vial, Henri; Calas, Michèle

    2005-05-19

    Three new series comprising 24 novel cationic choline analogues and consisting of mono- or bis (N or C-5-duplicated) thiazolium salts have been synthesized. Bis-thiazolium salts showed potent antimalarial activity (much superior to monothiazoliums). Among them, bis-thiazolium salts 12 and 13 exhibited IC(50) values of 2.25 nM and 0.65 nM, respectively, against P. falciparum in vitro. These compounds also demonstrated good in vivo activity (ED(50)

  12. Synthesis and antitumor activity of tetrahydrocarbazole hybridized with dithioate derivatives.

    PubMed

    El-Nassan, Hala Bakr

    2015-04-01

    The present study reported the synthesis of tetrahydrocarbazoles hybridized with dithioate derivatives. Three series were synthesized namely alkyl dithiocarbonates (4a-d), heterocyclic dithiocarbamates (6a-g) and dialkyl dithiocarbamate (7). The synthesized compounds were tested in vitro on human breast adenocarcinoma cell line (MCF7) and the human colon tumor cell line (HCT116). Most of the synthesized compounds exploited potent antitumor activity, especially compound 6f [4-chlorophenylpiperazine derivative], which showed cytotoxic activity against MCF7 superior to doxorubicin with IC50 value of 7.24 nM/mL. PMID:24899376

  13. Terpenoids with anti-inflammatory activity from Abies chensiensis.

    PubMed

    Zhao, Qian-Qian; Wang, Shu-Fang; Li, Ya; Song, Qiu-Yan; Gao, Kun

    2016-06-01

    The phytochemical investigation of Abies chensiensis led to the isolation and identification of nine new compounds including eight triterpenoids (1-8) and a new abietane-type diterpene (9), along with three known compounds (10-12). The absolute configuration of 9 was assigned by X-ray diffraction analysis. Compounds 1-11 were evaluated for the anti-inflammatory activity. Among the tested compounds, 1, 2, 5 and 6 exhibited potent inhibitory activity with IC50 values of 15.97, 18.73, 20.18 and 10.97μM, respectively. PMID:27080759

  14. Pharmacological screening of Hypericum androsaemum extracts for antioxidant, anti-lipid peroxidation, antiglycation and cytotoxicity activity.

    PubMed

    Saddiqe, Zeb; Maimoona, Alya; Abbas, Ghulam; Naeem, Ismat; Shahzad, Muhammad

    2016-03-01

    Oxidative stress and glycation processes have a combined effect on diabetes related complications. Crude plant extracts and plant derived compounds possessing both antiglycation and antioxidant activities have a high therapeutic potential for treating these complications. Antioxidant, antiglycation, anti-lipid per oxidation and cytotoxic activities of crude methanol extract and solvent fractions of Hypericum androsaemum L. (Hypericaceae) were evaluated and correlated with total content of phenolics and flavonoids. Significant radical scavenging activity was observed for the methanol extract against 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical used as a basis for antioxidant activity with IC50 value of 92.70±2.85 μg mL(-1) (96.20±2.34% inhibition at 500 μg mL(-1)). In case of anion scavenging activity the results were not very significant (33.20±1.22% inhibition at 500 μg mL(-1)). Anti-lipid per oxidation activity was highest for n-hexane fraction (67.83±1.33% inhibition at 500 μg mL(-1)) while the ethyl acetate fraction had the highest antiglycation activity (62.77±2.54% inhibition at 500 μg mL(-1)). Statistically significant correlation was determined for antioxidant and antiglycation activity and phenolic and flavonoid contents. In cytotoxicity assay all the extracts had IC50 values >30 μg mL(-1) as compared to the standard cycloheximide (IC50 value 0.084±0.1 μg mL(-1)). The polar extracts of H. androsaemum can be a good source of non-toxic compounds with antioxidant, anti-lipid per oxidation and antiglycation activities. PMID:27087068

  15. The Interplay of Scientific Activity, Worldviews and Value Outlooks

    NASA Astrophysics Data System (ADS)

    Lacey, Hugh

    2009-06-01

    Scientific activity tends to reflect particular worldviews and their associated value outlooks; and scientific results sometimes have implications for worldviews and the presuppositions of value outlooks. Even so, scientific activity per se neither presupposes nor provides sound rational grounds to accept any worldview or value outlook. Moreover, in virtue of reflecting a suitable variety of worldviews and value outlooks, perhaps including some religious ones, science is better able to further its aim. An extended argument is made that, although the materialist worldview has de facto been widely associated with the development of modern science, the scope of scientific inquiry is improperly limited when constraints, derived from materialism, are generally placed upon admissible scientific theories. Some implications for science education are sketched in the conclusion.

  16. Renin inhibition activity by chitooligosaccharides.

    PubMed

    Park, Pyo-Jam; Ahn, Chang-Bum; Jeon, You-Jin; Je, Jae-Young

    2008-04-01

    Six kinds of chitooligosaccharides (COSs) with different molecular weight (MW) and degree of deacetylation (DD) were prepared using ultrafiltration membrane reactor, and their renin inhibition modes were evaluated. All the COSs showed the renin-inhibitory activities with dose-dependent manner, and 90-COSs had the potent renin-inhibitory activity than that of 50-COSs. Among them, 90-MMWCOS (1000-5000Da) exhibits the highest activity with IC(50) value of 0.51mg/mL and acts as competitive inhibitor with K(i) value of 0.28mg/mL by Lineweaver-Burk and Dixon plots. These results indicated that DD value and MW of COSs are important factors affecting renin-inhibitory activity. PMID:18313296

  17. Synthesis of the vitamin E amino acid esters with an enhanced anticancer activity and in silico screening for new antineoplastic drugs.

    PubMed

    Gagic, Zarko; Ivkovic, Branka; Srdic-Rajic, Tatjana; Vucicevic, Jelica; Nikolic, Katarina; Agbaba, Danica

    2016-06-10

    Tocopherols and tocotrienols belong to the family of vitamin E (VE) with the well-known antioxidant properties. For certain α-tocopherol and γ-tocotrienol derivatives used as the lead compounds in this study, antitumor activities against various cancer cell types have been reported. In the course of the last decade, structural analogs of VE (esters, ethers and amides) with an enhanced antiproliferative and proapoptotic activity against various cancer cells were synthesized. Within the framework of this study, seven amino acid esters of α-tocopherol (4a-d) and γ-tocotrienol (6a-c) were prepared using the EDC/DMAP reaction conditions and their ability to inhibit proliferation of the MCF-7 and MDA-MB-231 breast cancer cells and the A549 lung cancer cells was evaluated. Compound 6a showed an activity against all three cell lines (IC50: 20.6μM, 28.6μM and 19μM for the MCF-7, MDA-MB-231 and A549 cells, respectively), while compound 4a inhibited proliferation of the MCF-7 (IC50=8.6μM) and A549 cells (IC50=8.6μM). Ester 4d exerted strong antiproliferative activity against the estrogen-unresponsive, multi-drug resistant MDA-MB-231 breast cancer cell line, with IC50 value of 9.2μM. Compared with the strong activity of compounds 4a, 4d and 6a, commercial α-tocopheryl succinate and γ-tocotrienol showed only a limited activity against all three cell lines, with IC50 values >50μM. Investigation of the cell cycle phase distribution and the cell death induction confirmed an apoptosis of the MDA-MB-231 cells treated with 4d, as well as a synergistic effect of 4d with the known anticancer drug doxorubicin. This result suggests a possibility of a combined therapy of breast cancer in order to improve the therapeutic response and to lower the toxicity associated with a high dose of doxorubicin. The stability study of 4d in human plasma showed that ca. 83% initial concentration of this compound remains in plasma in the course of six hours incubation. The ligand based

  18. Monoamine oxidase inhibitory activities of heterocyclic chalcones.

    PubMed

    Minders, Corné; Petzer, Jacobus P; Petzer, Anél; Lourens, Anna C U

    2015-11-15

    Studies have shown that natural and synthetic chalcones (1,3-diphenyl-2-propen-1-ones) possess monoamine oxidase (MAO) inhibition activities. Of particular importance to the present study is a report that a series of furanochalcones acts as MAO-B selective inhibitors. Since the effect of heterocyclic substitution, other than furan (and more recently thiophene, piperidine and quinoline) on the MAO inhibitory properties of the chalcone scaffold remains unexplored, the aim of this study was to synthesise and evaluate further heterocyclic chalcone analogues as inhibitors of the human MAOs. For this purpose, heterocyclic chalcone analogues that incorporate pyrrole, 5-methylthiophene, 5-chlorothiophene and 6-methoxypyridine substitution were examined. Seven of the nine synthesised compounds exhibited IC50 values <1 μM for the inhibition of MAO-B, with all compounds exhibiting higher affinities for MAO-B compared to the MAO-A isoform. The most potent MAO-B inhibitor (4h) displays an IC50 value of 0.067 μM while the most potent MAO-A inhibitor (4e) exhibits an IC50 value of 3.81 μM. It was further established that selected heterocyclic chalcones are reversible and competitive MAO inhibitors. 4h, however, may exhibit tight-binding to MAO-B, a property linked to its thiophene moiety. We conclude that high potency chalcones such as 4h represent suitable leads for the development of MAO-B inhibitors for the treatment of Parkinson's disease and possibly other neurodegenerative disorders. PMID:26432037

  19. Cytotoxicity, mode of action and antibacterial activities of selected Saudi Arabian medicinal plants

    PubMed Central

    2013-01-01

    Background The flora of Saudi Arabia is one of the richest biodiversity areas in the Arabian Peninsula and comprises very important genetic resources of crop and medicinal plants. The present study was designed to investigate the cytotoxicity and the antibacterial activities of the organic extracts from twenty six Saudi Arabian medicinal plants. The study was also extended to the investigation of the effects of the extracts from the four best plants, Ononis serrata (SY160), Haplophyllum tuberculatum (SY177), Pulicaria crispa (SY179), and Achillea beiberstenii (SY-200) on cell cycle distribution, apoptosis, caspases activities and mitochondrial function in leukemia CCRF-CEM cell line. Methods A resazurin assay was used to assess the cytotoxicity of the extracts on a panel of human cancer cell lines whilst the microbroth dilution was used to determine the minimal inhibitory concentration (MIC) of the samples against twelve bacterial strains belonging to four species, Escherichia coli, Enterobacter aerogenes, Klebsiella pneumoniae and Pseudomonas aeruginosa. Results The best activity on leukemia cell lines were recorded with SY177 (IC50 of 9.94 μg/mL) and SY179 (IC50 of 1.81 μg/mL) against CCRF-CEM as well as Ach-b (IC50 of 9.30 μg/mL) and SY160 (IC50 of 5.06 μg/mL) against HL60 cells. The extracts from SY177 and SY179 were also toxic against the seven solid cancer cell lines studied with the highest IC50 values of 31.64 μg/mL (SY177 against Hep-G2 cells). SY177 and Ach-b induced cell cycle arrest in G0/G1 and S phases whilst SY160 and SY179 induced arrest in G0/G1 phase. All the four plant extracts induced apoptosis in CCRF-CEM cells with the alteration of the mitochondrial membrane potential. In the antibacterial assays, only Ach-b displayed moderate antibacterial activities against E. coli and E. aerogenes ATCC strains (MIC of 256 μg/mL), AG100ATeT and K. pneumoniae ATCC strains (MIC of 128 μg/mL). Conclusions Finally, the results of the present

  20. Appraisal of biological activities and identification of phenolic compound of African marigold (Tagetes erecta) flower extract.

    PubMed

    Phrutivorapongkul, Ampai; Kiattisin, Kanokwan; Jantrawut, Pensak; Chansakaow, Sunee; Vejabhikul, Suwanna; Leelapornpisid, Pimporn

    2013-11-01

    The flowers of African marigold (Tagetes erecta L), a medicinal plant widely cultivated in Thailand, were subjected to evaluation for total phenolics, DPPH scavenging and thiobarbituric acid-reactive substance (TBARs) assays as well as tyrosinase inhibitory activity. In preliminary studies, the ethyl acetate (EA) extract obtained by continuous extraction showed the highest activities with highest phenolic content among all extracts. Bioassay-guided fractionation of EA extract led to isolation of a flavonoid identified as quercetagetin. Interestingly, it was found that quercetagetin exhibited potent DPPH scavenging activity with IC50 of 3.70 μg/ml which is about 2-3 times higher activity than standard quercetin (IC50 5.07 μg/ml) and trolox (IC50 9.93 μg/ml). Moreover, it exhibited tyrosinase inhibitory activity on L-tyrosine (IC50 89.31 μg/ml), higher than α- and β-arbutins (IC50 157.77 and 222.35 μg/ml) and slightly higher (IC50 128.41 μg/ml) than ellagic acid (IC50 151.1 μg/ml) when using L-DOPA as substrate. Testing with skin fibroblasts, all the extracts and quercetagetin demonstrated no toxic effect. These finding strongly indicate that African marigold flower is a promising source of natural antioxidative and tyrosinase inhibitory substances with safe to skin. PMID:24191339

  1. Design and synthesis of new tetrandrine derivatives and their antitumor activities.

    PubMed

    Wei, Xiao; Qu, Ting-Li; Yang, Yi-Fang; Xu, Jin-Fang; Li, Xu-Wen; Zhao, Zheng-Bao; Guo, Yue-Wei

    2016-10-01

    A series of tetrandrine derivatives were designed and synthesized using Suzuki coupling reaction. Eleven targeted compounds with over 50% inhibition against HL60 and A549 human cancer cell lines at 10 μM were further evaluated for the in vitro antitumor activities by MTT or SRB assay. The biological results revealed that some compounds exhibited potent antitumor activities. Thiophene derivative 6 and acetylphenyl derivative 5 were the most active ones against HL60 and A549 cell lines, with IC50 values less than 5 μM, which thus could be considered as useful candidate for further development of new antitumor agents. PMID:27244089

  2. Enantioselective synthesis and antioxidant activity of 3,4,5-substituted piperidine derivatives.

    PubMed

    Kim, Jin Ho; Shyam, Pranab K; Kim, Mi Jeong; Lee, Hwa-Jung; Lee, Jeong Tae; Jang, Hye-Young

    2016-07-01

    In this study, 3,4,5-trisubstituted piperidines were synthesized enantioselectively, and their antioxidant activity was evaluated. The 3,4,5-trisubstituted piperidines containing TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) and a spatially proximal hydroxy group showed good antioxidant activity. Some of these compounds showed IC50 values in a nanomolar range, comparable to that of TEMPO. Probably the TEMPO generated from the homolysis of the CON bond of 3,4,5-trisubstituted piperidines functions as a radical-scavenging entity, and the hydroxy group of piperidines has a synergistic effect to the antioxidant activity. PMID:27177825

  3. Accelerometer Output and MET Values of Common Physical Activities

    PubMed Central

    Kozey, Sarah L.; Lyden, Kate; Howe, Cheryl A.; Staudenmayer, John W.; Freedson, Patty S.

    2010-01-01

    Purpose This paper 1) provides the calibration procedures and methods for metabolic and activity monitor data collection, 2) compares measured MET values to the MET values from the Compendium of Physical Activities, and 3) examines the relationship between accelerometer output and METs for a range of physical activities Methods Participants (n=277) completed 11 activities for seven minutes each from a menu of 23 physical activities. Oxygen consumption (VO2) was measured using a portable metabolic system and an accelerometer was worn. MET values were defined as follows; measuredMETs (VO2/measured RMR) and standardMETs (VO2/3.5ml·kg·min−1). For the total sample and by sub-group (age [young <40y], sex and BMI [normal-weight <25 kg·m2]), measuredMETs and standardMETs were compared to the Compendium, using 95% confidence intervals to determine statistical significance (α=0.05). Average count·min−1 for each activity and the linear association between count·min−1 and METs are presented. Results Compendium METs were different than measured METs for 17/21 activities (81%). The number of activities different than the Compendium were similar between sub-groups or when standard METs were used. The average counts for the activities ranged from 11 counts·min−1(dishes) to 7490 counts·min−1 (2.23m·s−1, 3%) The r2 between counts and METs was 0.65. Conclusions This study provides valuable information about data collection, metabolic responses, and accelerometer output for common physical activities in a diverse participant sample. The Compendium should be updated with additional empirical data and linear regression models are inappropriate for accurately predicting METs from accelerometer output. PMID:20142781

  4. Biological activities of two macroalgae from Adriatic coast of Montenegro.

    PubMed

    Kosanić, Marijana; Ranković, Branislav; Stanojković, Tatjana

    2015-07-01

    In the present investigation the acetone extracts of macroalgae Ulva lactuca and Enteromorpha intestinalis were tested for antioxidant, antimicrobial and cytotoxic potential. Antioxidant activity was evaluated by measuring the scavenging capacity of tested samples on DPPH and superoxide anion radicals, reducing the power of samples and determination of total phenolic and flavonoid compounds in extracts. As a result of the study, U. lactuca extract was found to have a better free radical scavenging activity (IC50 = 623.58 μg/ml) than E. intestinalis extract (IC50 = 732.12 μg/ml). Moreover, the tested extracts had effective ferric reducing power and superoxide anion radical scavenging. The total content of phenol in extracts of U. lactuca and E. intestinalis was 58.15 and 40.68 μg PE/mg, while concentrations of flavonoids were 39.58 and 21.74 μg RE/mg, respectively. Furthermore, among the tested species, extracts of U. lactuca showed a better antimicrobial activity with minimum inhibitory concentration values ranging from 0.156 to 5 mg/ml, but it was relatively weak in comparison with standard antibiotics. Bacillus mycoides and Bacillus subtilis were the most susceptible to the tested extracts. Contrary to this Aspergillus flavus, Aspergillus fumigatus and Penicillium purpurescens were the most resistant. Finally, cytotoxic activity of tested extracts was evaluated on four human cancer cell lines. Extract of E. intestinalis expressed the stronger cytotoxic activity towards all tested cell lines with IC50 values ranging from 74.73 to 155.39 μg/ml. PMID:26150743

  5. Antiplasmodial activity of Cryptolepis sanguinolenta alkaloids from leaves and roots.

    PubMed

    Paulo, A; Gomes, E T; Steele, J; Warhurst, D C; Houghton, P J

    2000-02-01

    The roots of Cryptolepis sanguinolenta have been investigated for their chemical composition since 1931 but so far no studies on the leaves have been reported although they are used in traditional medicine in Guinea-Bissau. Two new alkaloids identified as cryptolepinoic acid (1) and methyl cryptolepinoate (2) and the known alkaloids cryptolepine (4), hydroxycryptolepine (5/5a) and quindoline (6), were isolated from the ethanolic and chlorophormic leaf extracts. Aqueous and ethanolic extracts of the leaves and roots and seven alkaloids isolated from those extracts were tested in vitro against Plasmodium falciparum K1 (multidrug-resistant strain) and T996 (chloroquine-sensitive clone). All the extracts were shown to give 90% inhibition of P. falciparum K1 growth at concentrations < 23 micrograms/ml. Cryptolepine (4) was the most active alkaloid tested with IC50 values (0.23 microM to K1; 0.059 microM to T996) comparable with chloroquine (0.26 microM to K1; 0.019 microM to T996). The indolobenzazepine alkaloid cryptoheptine (7) was the second most active with IC50 values of 0.8 microM (K1) and 1.2 microM (T996). Cryptolepinoic acid (1) showed no significant activity while its ethyl ester derivative 3 was active against P. falciparum K1 (IC50 = 3.7 microM). All the indoloquinoline alkaloids showed cross-resistance with chloroquine but not the indolobenzazepine alkaloid 7. It was noticed that alkaloids with weakly basic characteristics were active whereas other structurally related alkaloids with different acid-base profiles were inactive. These observations are in agreement with the antimalarial mechanism of action for quinolines. PMID:10705730

  6. Categorizing Pedagogical Patterns by Teaching Activities and Pedagogical Values

    ERIC Educational Resources Information Center

    Bennedsen, Jens; Eriksen, Ole

    2006-01-01

    The main contribution of this paper is a proposal for a universal pedagogical pattern categorization based on teaching values and activities. This categorization would be more sustainable than the arbitrary categorization implied by pedagogical pattern language themes. Pedagogical patterns from two central patterns languages are analyzed and…

  7. Angiotensin-converting enzyme inhibitory and antioxidant activities of enzymatically synthesized phenolic and vitamin glycosides.

    PubMed

    Charles, Rajachristu Einstein; Ponrasu, Thangavel; Sivakumar, Ramaiah; Divakar, Soundar

    2009-03-01

    Amyloglucosidase from Rhizopus mould and beta-glucosidase from sweet almond were employed for the preparation of phenolic and vitamin glycosides of vanillin, N-vanillylnonanamide, DL-dopa, dopamine, curcumin, alpha-tocopherol (vitamin E), pyridoxine (vitamin B(6)), ergocalciferol (vitamin D(2)), thiamin (vitamin B(1)) and riboflavin (vitamin B(2)). Approx. 20 enzymatically prepared phenolic and vitamin glycosides were subjected to ACE (angiotensin-converting enzyme) inhibition activity measurements, and 14 glycosides were tested for antioxidant activities. Both phenolic and vitamin glycosides exhibited IC(50) values for ACE inhibition in the 0.52+/-0.03-3.33+/-0.17 mM range and antioxidant activities ranging from 0.8+/-0.04 to 1.18+/-0.06 mM. Comparable ACE inhibition values were observed between free phenols and vitamin glycosides. However, antioxidant activities of glycosides were, in general, lesser than those of free phenols. Best IC(50) value for ACE inhibition were observed for 11-O-(D-fructofuranosyl)thiamin (0.52+/-0.03 mM), 3-hydroxy-4-O-(6-D-sorbitol)phenylalanine (0.56+/-0.03 mM), 4-O-(beta-D-glucopyranosyl)vanillin (0.61+/-0.03 mM), 4-O-(D-galactopyranosyl)vanillin (0.61+/-0.03 mM) and pyridoxine-D-glucoside (0.84+/-0.04 mM). Similarly, best IC(50) values for antioxidant activity were observed for 1,7-O-(bis-beta-D-glucopyranosyl)curcumin (0.8+/-0.04 mM), 4-O-(beta-D-glucopyranosyl)vanillin (0.9+/-0.05 mM), 3-hydroxy-4-O-(beta-D-galactopyranosyl-(1'-->4)beta-D-glucopyranosyl)phenylalanine (0.9+/-0.05 mM), 20-O-(D-glucopyranosyl)ergocalciferol (0.9+/-0.05 mM) and dopamine-D-galactoside (0.93+/-0.05 mM). PMID:18547170

  8. Synthesis and p38 Inhibitory Activity of Some Novel Substituted N,N'-Diarylurea Derivatives.

    PubMed

    Zhu, Dianxi; Xing, Qifeng; Cao, Ruiyuan; Zhao, Dongmei; Zhong, Wu

    2016-01-01

    We have identified a novel series of substituted N,N'-diarylurea p38α inhibitors. The inhibitory activity of the target compounds against the enzyme p38α, MAPKAPK2 in BHK cells, TNF-α release in LPS-stimulated THP-1 cells and p38α binding experiments were tested. Among these compounds, 25a inhibited the p38α enzyme with an IC50 value of 0.47 nM and a KD value of 1.54 × 10(-8) and appears to be the most promising one in the series. PMID:27223276

  9. Inhibitory effect of Andrographis paniculata extract and its active diterpenoids on platelet aggregation.

    PubMed

    Thisoda, Piengpen; Rangkadilok, Nuchanart; Pholphana, Nanthanit; Worasuttayangkurn, Luksamee; Ruchirawat, Somsak; Satayavivad, Jutamaad

    2006-12-28

    Andrographis paniculata has been widely used for the prevention and treatment of common cold especially in Asia and Scandinavia. The three active diterpenoids from this plant, including aqueous plant extracts, were investigated for the inhibitory effect on platelet aggregation in vitro. The results indicated that andrographolide (AP(1)) and 14-deoxy-11,12-didehydroandrographolide (AP(3)) significantly inhibited thrombin-induced platelet aggregation in a concentration-(1-100 microM) and time-dependent manner while neoandrographolide (AP(4)) had little or no activity. AP(3) exhibited higher antiplatelet activity than AP(1) with IC(50) values ranging from 10 to 50 microM. The inhibitory mechanism of AP(1) and AP(3) on platelet aggregation was also evaluated and the results indicated that the inhibition of extracellular signal-regulated kinase1/2 (ERK1/2) pathway may contribute to antiplatelet activity of these two compounds. In addition, standardized aqueous extracts of A. paniculata containing different amounts of AP(3) inhibited thrombin-induced aggregation to different degrees. The extracts significantly decreased platelet aggregation in a concentration-(10-100 microg/ml) and time-dependent manner. However, the extract with high level of AP(3) (Extract B) (IC(50) values=50-75 microg/ml) showed less inhibitory activity against thrombin than the extract with lower level of AP(3) (Extract A) (IC(50) values=25-50 microg/ml). These results indicate that the standardized A. paniculata extract may contain other antiplatelet compounds rather than AP(1) and AP(3), which contribute to high antiplatelet activity. Therefore, the consumption of A. paniculata products may help to prevent or treat some cardiovascular disorders i.e. thrombosis; however, it should be used with caution by patients with bleeding disorders. PMID:17081514

  10. Substituted thieno[2,3-b]thiophenes and related congeners: Synthesis, β-glucuronidase inhibition activity, crystal structure, and POM analyses.

    PubMed

    Mabkhot, Yahia Nasser; Barakat, Assem; Yousuf, Sammer; Choudhary, M Iqbal; Frey, Wolfgang; Ben Hadda, Taibi; Mubarak, Mohammad S

    2014-12-01

    A series of 15 novel compounds incorporating the thieno[2,3-b]thiophene moiety were synthesized. The chemical structures of these compounds were deduced from elemental analyses, (1)H NMR, (13)C NMR, and ESI-mass spectral data. The enzyme inhibition potential of these compounds was evaluated, in vitro, against β-glucuronidase, xanthine oxidase, and α-chymotrypsin enzymes. The cytotoxicity was evaluated by a cell viability assay utilizing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. Among the compounds tested, compound 3 was the most potent β-glucuronidase inhibitor with an IC50 value of 0.9 ± 0.0138 μM; it was much more active than the standard, d-saccharic acid 1,4-lactone (IC50=45.75 ± 2.16 μM). Compound 12, on the other hand, was the most potent as a xanthine oxidase inhibitor with an IC50 of 14.4 ± 1.2 μM. With the characterization of their mechanism of action and with further testing, these compounds could be useful candidates as anticancer drugs. In addition, the newly synthesized compounds were subjected to POM analyses to get insights about their degree of their toxicity. PMID:25245672

  11. Synthesis and anti-acetylcholinesterase activity of scopoletin derivatives.

    PubMed

    Khunnawutmanotham, Nisachon; Chimnoi, Nitirat; Saparpakorn, Patchreenart; Techasakul, Supanna

    2016-04-01

    A series of scopoletin derivatives incorporated with the pyridinium moiety was synthesized and evaluated for their acetylcholinesterase (AChE) inhibitory activity by the colorimetric Ellman's method. A 2-fluorobenzylpyridinium derivative was the most potent among the tested compounds, with an IC50 value of 0.215±0.015μM, which was greatly improved from that of scopoletin. Docking studies revealed that the scopoletin portion of the mentioned compound was bound to the peripheral anionic site of the AChE, whereas the N-benzylpyridinium residue to the catalytic anionic site. PMID:26943478

  12. Cytotoxic and Antimigratory Activities of Phenolic Compounds from Dendrobium brymerianum

    PubMed Central

    Klongkumnuankarn, Pornprom; Busaranon, Kesarin; Chanvorachote, Pithi; Sritularak, Boonchoo; Jongbunprasert, Vichien; Likhitwitayawuid, Kittisak

    2015-01-01

    Chromatographic separation of a methanol extract prepared from the whole plant of Dendrobium brymerianum led to the isolation of eight phenolic compounds. Among the isolated compounds (1–8), moscatilin (1), gigantol (3), lusianthridin (4), and dendroflorin (6) showed appreciable cytotoxicity against human lung cancer cell lines with IC50 values of 196.7, 23.4, 65.0, and 125.8 μg/mL, respectively, and exhibited antimigratory property at nontoxic concentrations. This study is the first report on the biological activities of this plant. PMID:25685168

  13. neo-Clerodane diterpenoids from Scutellaria barbata with cytotoxic activities.

    PubMed

    Dai, Sheng-Jun; Tao, Jia-Yi; Liu, Ke; Jiang, Yong-Tao; Shen, Li

    2006-07-01

    Three neo-clerodane diterpenoids, named barbatins A-C (1-3), and the neo-clerodane diterpenoid nicotinyl ester, named scutebarbatine B (4), were isolated from the whole plant of Scutellaria barbata D. Don. Their structures were elucidated by spectroscopic analyses (UV, IR, HRFAB-MS, 1D NMR and 2D NMR). In vitro, compounds 1-4 showed significant cytotoxic activities against three human cancer lines, namely, HONE-1 nasopharyngeal, KB oral epidermoid carcinoma, and HT29 colorectal carcinoma cells, with IC50 values in the range 3.5-8.1 microM. PMID:16769097

  14. Biological activities of xanthatin from Xanthium strumarium leaves.

    PubMed

    Nibret, Endalkachew; Youns, Mahamoud; Krauth-Siegel, R Luise; Wink, Michael

    2011-12-01

    The objective of the present work was to evaluate the biological activities of the major bioactive compound, xanthatin, and other compounds from Xanthium strumarium (Asteraceae) leaves. Inhibition of bloodstream forms of Trypanosoma brucei brucei and leukaemia HL-60 cell proliferation was assessed using resazurin as a vital stain. Xanthatin was found to be the major and most active compound against T. b. brucei with an IC(50) value of 2.63 µg/mL and a selectivity index of 20. The possible mode of action of xanthatin was further evaluated. Xanthatin showed antiinflammatory activity by inhibiting both PGE(2) synthesis (24% inhibition) and 5-lipoxygenase activity (92% inhibition) at concentrations of 100 µg/mL and 97 µg/mL, respectively. Xanthatin exhibited weak irreversible inhibition of parasite specific trypanothione reductase. Unlike xanthatin, diminazene aceturate and ethidium bromide showed strong DNA intercalation with IC(50) values of 26.04 µg/mL and 44.70 µg/mL, respectively. Substantial induction of caspase 3/7 activity in MIA PaCa-2 cells was observed after 6 h of treatment with 100 µg/mL of xanthatin. All these data taken together suggest that xanthatin exerts its biological activity by inducing apoptosis and inhibiting both PGE(2) synthesis and 5-lipoxygenase activity thereby avoiding unwanted inflammation commonly observed in diseases such as trypanosomiasis. PMID:21953905

  15. Synthesis, characterization, and antioxidant/cytotoxic activity of new chromone Schiff base nano-complexes of Zn(II), Cu(II), Ni(II) and Co(II)

    NASA Astrophysics Data System (ADS)

    Saif, M.; El-Shafiy, Hoda F.; Mashaly, Mahmoud M.; Eid, Mohamed F.; Nabeel, A. I.; Fouad, R.

    2016-08-01

    A chromone Schiff base complexes of Zn(II) (1), Cu(II) (2), Ni(II) (3) and Co(II) (4) were successfully prepared in nano domain with crystalline or amorphous structures. The spectroscopic data revealed that the Schiff base ligand behaves as a monoanionic tridentate ligand. The metal complexes exhibited octahedral geometry. Transmission electron microscope (TEM) analysis showed that Cu(II) complex have aggregated nanospheres morphology. The obtained nano-complexes were tested as antioxidant and antitumor agents. The H2L and its Cu(II) complex (2) were found to be more potent antioxidant (IC50(H2L) = 0.93 μM; IC50(Cu(II) complex) = 1.1 μM than standard ascorbic acid (IC50 = 2.1 μM) as evaluated by DPPH• method. The H2L and its complexes (1-4) were tested for their in vitro cytotoxicity against Ehrlich Ascites Carcinoma cell line (EAC). The Cu(II) nano-complex (2) effectively inhibited EAC growth with IC50 value of 47 μM in comparison with its parent compound and other prepared complexes. The high antioxidant activity and antitumor activity of Cu(II) nano-complex (2) were attributed to their chemical structure, Cu(II) reducing capacity, and nanosize property. The toxicity test on mice showed that Zn(II) (1) and Cu(II) (2) nano-complex have lower toxicity than the standard cis-platin.

  16. Antitrypanosomal activity of 5-nitro-2-aminothiazole-based compounds.

    PubMed

    Papadopoulou, Maria V; Bloomer, William D; Rosenzweig, Howard S; Wilkinson, Shane R; Szular, Joanna; Kaiser, Marcel

    2016-07-19

    A small series of 5-nitro-2-aminothiazole-based amides containing arylpiperazine-, biphenyl- or aryloxyphenyl groups in their core were synthesized and evaluated as antitrypanosomatid agents. All tested compounds were active or moderately active against Trypanosoma cruzi amastigotes in infected L6 cells and Trypanosoma brucei brucei, four of eleven compounds were moderately active against Leishmania donovani axenic parasites while none were deemed active against T. brucei rhodesiense. For the most active/moderately active compounds a moderate selectivity against each parasite was observed. There was good correlation between lipophilicity (clogP value) and antileishmanial activity or toxicity against L6 cells. Similarly, good correlation existed between clogP values and IC50 values against T. cruzi in structurally related subgroups of compounds. Three compounds were more potent as antichagasic agents than benznidazole but were not activated by the type I nitrorectusase (NTR). PMID:27092415

  17. Chemical modification and structure-activity relationships of pyripyropenes. 3. Synthetic conversion of pyridine-pyrone moiety.

    PubMed

    Obata, R; Sunazuka, T; Tian, Z; Tomoda, H; Harigaya, Y; Omura, S

    1997-03-01

    Structure-activity relationships of the pyridine-pyrone moiety in pyripyropene A (1), a potent acyl-CoA: cholesterol acyltransferase (ACAT) inhibitor of fungal origin, were studied. Several kinds of aromatic or hetero ring substituents for the pyridine moiety were synthesized using unique degradation reaction, following by gamma-acylation. All the six synthesized analogs decreased the inhibitory activity with 20 to 200 times larger IC50 values than that of 1. Furthermore, the pyridine-pyrone substituent also dramatically decrease the inhibitory activity. Thus, the pyridine-pyrone moiety is important for eliciting potent ACAT inhibition. PMID:9127194

  18. Chemical modification and structure-activity relationships of pyripyropenes. 3. Synthetic conversion of pyridine-pyrone moiety

    PubMed

    Obata; Sunazuka; Tian; Tomoda; Harigaya; Omura

    1997-03-01

    Structure-activity relationships of the pyridine-pyrone moiety in pyripyropene A (1), a potent acyl-CoA : cholesterol acyltransferase (ACAT) inhibitor of fungal origin, were studied. Several kinds of aromatic or hetero ring substituents for the pyridine moiety were synthesized using unique degradation reaction, following by gamma-acylation. All the six synthesized analogs decreased the inhibitory activity with 20 to 200 times larger IC50 values than that of 1. Furthermore, the pyridine-pyrone substituent also dramatically decrease the inhibitory activity. Thus, the pyridine-pyrone moiety is important for eliciting potent ACAT inhibition. PMID:9439694

  19. Anti-Protozoal Activities of Cembrane-Type Diterpenes from Vietnamese Soft Corals.

    PubMed

    Thao, Nguyen Phuong; Luyen, Bui Thi Thuy; Brun, Reto; Kaiser, Marcel; Van Kiem, Phan; Van Minh, Chau; Schmidt, Thomas J; Kang, Jong Seong; Kim, Young Ho

    2015-01-01

    Based on our previous finding that certain cembranoid diterpenes possess selective toxicity against protozoan pathogens of tropical diseases such as Trypanosoma and Plasmodium, we have subjected a series of 34 cembranes isolated from soft corals living in the Vietnamese sea to an in vitro screening for anti-protozoal activity against Trypanosoma brucei rhodesiense (Tbr), T. cruzi (Tc), Leishmania donovani (Ld), and Plasmodium falciparum (Pf). Twelve of the tested compounds displayed significant activity against at least one of the parasites. Specifically, 7S,8S-epoxy-1,3,11-cembratriene-16-oic methyl ester (1), (1R,4R,2E,7E,11E)-cembra-2,7,11-trien-4-ol (2), crassumol D (12), crassumol E (13), and (1S,2E,4S,6E,8S,11S)-2,6,12(20)-cembrantriene-4,8,11-triol (16) from Lobophytum crassum, L. laevigatum, and Sinularia maxima showed the highest level of inhibitory activity against T. b. rhodesiense, with IC50 values of about 1 µM or less. Lobocrasol A (6) and lobocrasol C (8) from L. crassum and L. laevigatum exhibited particularly significant inhibitory effects on L. donovani with IC50 values < 0.2 µM. The best antiplasmodial effect was exerted by laevigatol A (10), with an IC50 value of about 3.0 µM. The cytotoxicity of the active compounds on L6 rat skeletal myoblast cell was also assessed and found to be insignificant in all cases. This is the first report on anti-protozoal activity of these compounds, and points out the potential of the soft corals in discovery of new anti-protozoal lead compounds. PMID:26184133

  20. In Vitro Activity of Mirincamycin (U24729A) against Plasmodium falciparum Isolates from Gabon▿

    PubMed Central

    Held, Jana; Westerman, Richard; Kremsner, Peter G.; Mordmüller, Benjamin

    2010-01-01

    We assessed the in vitro activity of mirincamycin, a lincosamide antibiotic, against Plasmodium falciparum clinical isolates from Gabon. Growth was determined by HRP2 enzyme-linked immunosorbent assay using an adapted protocol with a prolonged incubation time (6 days) to account for antibiotic-induced delayed death. Mirincamycin's cis and trans isomers are more active (median 50% inhibitory concentrations [IC50s], 3.2 nM and 2.6 nM) than the comparator drugs clindamycin (IC50, 12 nM) and doxycycline (IC50, 720 nM), and therefore, further clinical development is promising. PMID:19841147

  1. In vitro activity of mirincamycin (U24729A) against Plasmodium falciparum isolates from Gabon.

    PubMed

    Held, Jana; Westerman, Richard; Kremsner, Peter G; Mordmüller, Benjamin

    2010-01-01

    We assessed the in vitro activity of mirincamycin, a lincosamide antibiotic, against Plasmodium falciparum clinical isolates from Gabon. Growth was determined by HRP2 enzyme-linked immunosorbent assay using an adapted protocol with a prolonged incubation time (6 days) to account for antibiotic-induced delayed death. Mirincamycin's cis and trans isomers are more active (median 50% inhibitory concentrations [IC(50)s], 3.2 nM and 2.6 nM) than the comparator drugs clindamycin (IC(50), 12 nM) and doxycycline (IC(50), 720 nM), and therefore, further clinical development is promising. PMID:19841147

  2. Antioxidant, antimalarial and antimicrobial activities of tannin-rich fractions, ellagitannins and phenolic acids from Punica granatum L.

    PubMed

    Reddy, Muntha K; Gupta, Sashi K; Jacob, Melissa R; Khan, Shabana I; Ferreira, Daneel

    2007-05-01

    The Punica granatum L. (pomegranate) by-product POMx was partitioned between water, EtOAc and n-BuOH, and the EtOAc and n-BuOH extracts were purified by XAD-16 and Sephadex LH-20 column chromatography to afford ellagic acid (1), gallagic acid (2), punicalins (3), and punicalagins (4). Compounds 1 - 4 and the mixture of tannin fractions (XAD-16 eluates) were evaluated for antioxidant, antiplasmodial, and antimicrobial activities in cell-based assays. The mixture of tannins (TPT), XAD-EtOAc, XAD-H2O, XAD-PJ and XAD-BuOH, exhibited IC50 values against reactive oxygen species (ROS) generation at 0.8 - 19 microg/mL. Compounds 1 - 4 showed IC50 values of 1.1, 3.2, 2.3 and 1.4 microM, respectively, against ROS generation and no toxicity up to 31.25 microg/mL against HL-60 cells. Gallagic acid (2) and punicalagins (4) exhibited antiplasmodial activity against Plasmodium falciparum D6 and W2 clones with IC50 values of 10.9, 10.6, 7.5 and 8.8 microM, respectively. Fractions XAD-EtOAc, XAD-BuOH, XAD-H2O and XAD-PJ compounds 1 - 4 revealed antimicrobial activity when assayed against Escherichia coli, Pseudomonas aeruginosa, Candida albicans, Cryptococcus neoformans, methicillin-resistant Staphylococcus aureus (MRSA), Aspergillus fumigatus and Mycobacterium intracellulare. Compounds 2 and 4 showed activity against P. aeruginosa, C. neoformans, and MRSA. This is the first report on the antioxidant, antiplasmodial and antimicrobial activities of POMx isolates, including structure-activity relationships (SAR) of the free radical inhibition activity of compounds 1 - 4. Our results suggest a beneficial effect from the daily intake of POMx and pomegranate juice (PJ) as dietary supplements to augment the human immune system's antioxidant, antimalarial and antimicrobial capacities. PMID:17566148

  3. In vitro antiplasmodial activity and cytotoxicity of ethnobotanically selected Ivorian plants.

    PubMed

    Vonthron-Sénécheau, Catherine; Weniger, Bernard; Ouattara, Modibo; Bi, Fezan Tra; Kamenan, Alphonse; Lobstein, Annelise; Brun, Reto; Anton, Robert

    2003-08-01

    Eight extracts from four Ivorian medicinal plants, traditionally used to treat malaria, were tested for their antiplasmodial activity in vitro by assessing their ability to inhibit the uptake of [3H]hypoxanthine into the Plasmodium falciparum K1 chloroquine-resistant strain. The most active extract was the methylene chloride extract of Anogeissus leiocarpus which exhibited an IC(50) value of 3.8 micro g/ml. Inhibition of the growth of Plasmodium falciparum was also observed with the methylene chloride extract of Cochlospermum planchonii and Microdesmis keayana as well as with both methylene chloride and methanolic extracts of Hymenocardia acida. PMID:12860312

  4. Antiplasmodial activity of compounds from the surface exudates of Senecio roseiflorus.

    PubMed

    Kerubo, Leonidah Omosa; Midiwo, Jacob Ogweno; Derese, Solomon; Langat, Moses K; Akala, Hosea M; Waters, Norman C; Peter, Martin; Heydenreich, Matthias

    2013-02-01

    From the surface exudates of Senecio roseiflorus fourteen known methylated flavonoids and one phenol were isolated and characterized. The structures of these compounds were determined on the basis of their spectroscopic analysis. The surface exudate and the flavonoids isolated showed moderate to good antiplasmodial activity with 5,4'-dihydroxy-7-dimethoxyflavanone having the highest activity against chloroquine-sensitive (D6) and resistant (W2) strains of Plasmodium falciparum, with IC50 values of 3.2 +/- 0.8 and 4.4 +/- 0.01 microg/mL respectively. PMID:23513721

  5. Molecular modeling based synthesis and evaluation of in vitro anticancer activity of indolyl chalcones.

    PubMed

    Gaur, Rashmi; Yadav, Dharmendra K; Kumar, Shiv; Darokar, Mahendra P; Khan, Feroz; Bhakuni, Rajendra Singh

    2015-01-01

    A series of twenty one chalcone derivatives having indole moiety were synthesized and were evaluated against four human cancer cell lines. Indolyl chalcones 1a, 1b, 1d, 1f-1j, 2c, 2e, 2i showed good anticancer activity. Chalcones 1b and 1d were the most active and selective anticancer agents with IC50 values <1μg/ml and 1.51μg/ml, against WRL-68 cell line, respectively. Molecular mechanism was explored through in silico docking & ADMET studies. PMID:25860176

  6. Anti-allergic activity of compounds from Kaempferia parviflora.

    PubMed

    Tewtrakul, Supinya; Subhadhirasakul, Sanan; Kummee, Sopa

    2008-02-28

    Kaempferia parviflora is one of the plants in the Zingiberaceae family, locally known in Thai as kra-chai-dam. In Thai traditional medicine, the decoction of Kaempferia parviflora powder with alcohol has been reported to cure allergy, asthma, impotence, gout, diarrhea, dysentery, peptic ulcer and diabetes. Therefore, the present study aimed to investigate anti-allergic substances from this plant. Bioassay-guided fractionation led to the isolation of seven methoxyflavone derivatives (1-7) from Kaempferia parviflora extract and they were identified on the basis of spectroscopic methods. Among the compounds tested, 5-hydroxy-3,7,3',4'-tetramethoxyflavone (5) possessed the highest anti-allergic activity against antigen-induced beta-hexosaminidase release as a marker of degranulation in RBL-2H3 cells with an IC(50) value of 8.0 microM, followed by 5-hydroxy-7-methoxyflavone (2, IC(50)=20.6 microM) and 5-hydroxy-7,4'-dimethoxyflavone (4, IC(50)=26.0 microM), whereas others showed moderate activities (IC(50)=37.5-66.5 microM). Structure-activity trends of 7-methoxyflavone derivatives on anti-allergic activity can be summarized as follows: (1) substitution with vicinal methoxyl groups at positions 3' and 4' conferred higher activity than only one methoxylation, (2) methoxylation at position 3 reduced activity and (3) methoxylation at position 5 showed higher activity than hydroxylation. Compounds 2, 4 and 5 were also determined for their mechanisms on ionomycin-induced beta-hexosaminidase release. The results indicated that the mechanism on inhibition of cell degranulation of compounds 2 and 5 mainly involve the inhibition of Ca(2+) influx to the cells, whereas that of 4 may be partly due to this inhibition. In regards to the active constituents for anti-allergic activity of Kaempferia parviflora, 5-hydroxy-3,7,3',4'-tetramethoxyflavone (5), 5-hydroxy-7-methoxyflavone (2) and 5-hydroxy-7,4'-dimethoxyflavone (4) are responsible for anti-allergic effect of this plant. The

  7. Identification of ponatinib and other known kinase inhibitors with potent MEKK2 inhibitory activity.

    PubMed

    Ahmad, Syed; Johnson, Gary L; Scott, John E

    2015-08-01

    The kinase MEKK2 (MAP3K2) may play an important role in tumor growth and metastasis for several cancer types. Thus, targeting MEKK2 may represent a novel strategy for developing more effective therapies for cancer. In order to identify small molecules with MEKK2 inhibitory activity, we screened a collection of known kinase inhibitors using a high throughput MEKK2 intrinsic ATPase enzyme assay and confirmed activity of the most potent hits with this primary assay. We also confirmed activities of these known kinase inhibitors with an MEKK2 transphosphorylation slot blot assay using MKK6 as a substrate. We observed a good correlation in potencies between the two orthogonal MEKK2 kinase activity assay formats for this set of inhibitors. We report that ponatinib, AT9283, AZD7762, JNJ-7706621, PP121 and hesperadin had potent MEKK2 enzyme inhibitory activities ranging from 4.7 to 60 nM IC50. Ponatinib is an FDA-approved drug that potently inhibited MEKK2 enzyme activity with IC50 values of 10-16 nM. AT9283 is currently in clinical trials and produced MEKK2 IC50 values of 4.7-18 nM. This set of known kinase inhibitors represents some of the most potent in vitro MEKK2 inhibitors reported to date and may be useful as research tools. Although these compounds are not selective for MEKK2, the structures of these compounds give insight into pharmacophores that potently inhibit MEKK2 and could be used as initial leads to design highly selective inhibitors of MEKK2. PMID:26056008

  8. Cytotoxic Activity of Piper cubeba Extract in Breast Cancer Cell Lines

    PubMed Central

    Graidist, Potchanapond; Martla, Mananya; Sukpondma, Yaowapa

    2015-01-01

    This study aimed to evaluate the cytotoxicity of a crude extract of Piper cubeba against normal and breast cancer cell lines. To prepare the extract, P. cubeba seeds were ground, soaked in methanol and dichloromethane and isolated by column chromatography. Fractions were tested for cytotoxicity effects on normal fibroblast (L929), normal breast (MCF-12A) and breast cancer cell lines (MCF-7, MDA-MB-468 and MDA-MB-231). The most effective fraction was selected for DNA fragmentation assay to detect apoptotic activity. The results showed that the methanolic crude extract had a higher cytotoxic activity against MDA-MB-468 and MCF-7 than a dichloromethane crude extract. Then, the methanolic crude extract was separated into six fractions, designated A to F. Fraction C was highly active against breast cancer cell lines with an IC50 value less than 4 μg/mL. Therefore, Fraction C was further separated into seven fractions, CA to CG. The 1H-NMR profile showed that Fraction CE was long chain hydrocarbons. Moreover, Fraction CE demonstrated the highest activity against MCF-7 cells with an IC50 value of 2.69 ± 0.09 μg/mL and lower cytotoxicity against normal fibroblast L929 cells with an IC50 value of 4.17 ± 0.77 μg/mL. Finally, DNA fragmentation with a ladder pattern characteristic of apoptosis was observed in MCF-7, MDA-MB-468, MDA-MB-231 and L929 cells, but not in MCF-12A cells. PMID:25867951

  9. Cytotoxic activity of Piper cubeba extract in breast cancer cell lines.

    PubMed

    Graidist, Potchanapond; Martla, Mananya; Sukpondma, Yaowapa

    2015-04-01

    This study aimed to evaluate the cytotoxicity of a crude extract of Piper cubeba against normal and breast cancer cell lines. To prepare the extract, P. cubeba seeds were ground, soaked in methanol and dichloromethane and isolated by column chromatography. Fractions were tested for cytotoxicity effects on normal fibroblast (L929), normal breast (MCF-12A) and breast cancer cell lines (MCF-7, MDA-MB-468 and MDA-MB-231). The most effective fraction was selected for DNA fragmentation assay to detect apoptotic activity. The results showed that the methanolic crude extract had a higher cytotoxic activity against MDA-MB-468 and MCF-7 than a dichloromethane crude extract. Then, the methanolic crude extract was separated into six fractions, designated A to F. Fraction C was highly active against breast cancer cell lines with an IC50 value less than 4 μg/mL. Therefore, Fraction C was further separated into seven fractions, CA to CG. The 1H-NMR profile showed that Fraction CE was long chain hydrocarbons. Moreover, Fraction CE demonstrated the highest activity against MCF-7 cells with an IC50 value of 2.69 ± 0.09 μg/mL and lower cytotoxicity against normal fibroblast L929 cells with an IC50 value of 4.17 ± 0.77 μg/mL. Finally, DNA fragmentation with a ladder pattern characteristic of apoptosis was observed in MCF-7, MDA-MB-468, MDA-MB-231 and L929 cells, but not in MCF-12A cells. PMID:25867951

  10. Yam (Dioscorea batatas) tuber mucilage exhibited antioxidant activities in vitro.

    PubMed

    Hou, Wen-Chi; Hsu, Feng-Lin; Lee, Mei-Hsien

    2002-12-01

    The yam (Dioscorea batatas Decne) tuber mucilage (YTM) was extracted and partially purified by SDS and heating treatments. This purified YTM exhibited antioxidant activities in a series of in vitro tests, including 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical (half-inhibition concentration, IC 50, was 0.86 mg/mL) and hydroxyl radical (IC 50 was 22 microg/mL) scavenging activity assays, reducing power test, anti-lipid peroxidation and anti-human low density lipoprotein peroxidation tests (IC 50 was 145.46 microg/mL) using butylated hydroxytoluene (BHT), reduced glutathione, or ascorbic acid for comparisons. With electron paramagnetic resonance (EPR) spectrometry for DPPH radical detection, the intensities of the EPR signals were decreased by the increased amounts of YTM added (IC 50 was 1.62 mg/mL). These results suggest that mucilage of yam tuber might play roles as antiradicals and antioxidants. PMID:12494332

  11. Evaluation of in vitro antioxidant, antimicrobial, genotoxic and anticancer activities of lichen Cetraria islandica.

    PubMed

    Grujičić, Darko; Stošić, Ivana; Kosanić, Marijana; Stanojković, Tatjana; Ranković, Branislav; Milošević-Djordjević, Olivera

    2014-10-01

    In this study, the antioxidant, antimicrobial, genotoxic and anticancer activities of Cetraria islandica methanol extract were determined by using free radical and superoxide anion scavenging activity, reducing power, determination of total phenolic compounds and flavonoid contents, broth microdilution minimal inhibitory concentration against five bacterial and five fungal species, cytokinesis block micronucleus (MN) assay on peripheral blood lymphocytes (PBLs) and the microculture tetrazolium test on FemX (human melanoma) and LS174 (human colon carcinoma) cell lines. As a result of the study, we found that C. islandica methanol extract exhibited moderate free-radical-scavenging activity with IC50 values 678.38 μg/ml. Moreover, the tested extract had effective reducing power and superoxide anion radical scavenging. The minimal inhibitory concentration values against the tested microorganisms ranged from 0.312 to 5 mg/ml. The extract increased MN frequency in a dose dependent manner, but it was significant in higher tested concentrations (50, 100 and 200 μg/ml). No significant differences were observed between NDI values in all treatments and untreated PBLs. In addition, the tested extract had strong anticancer activity towards both cell lines with IC50 values of 22.68 and 33.74 μg/ml. It can be concluded that the tested extract exhibited a certain level of in vitro antioxidant, antimicrobial, genotoxic and anticancer activities. PMID:24590925

  12. Investigation of cytotoxic activity in four stachys species from iran.

    PubMed

    Khanavi, Mahnaz; Manayi, Azadeh; Lotfi, Mahnaz; Abbasi, Rofeyde; Majdzadeh, Maryam; Ostad, Seyed Nasser

    2012-01-01

    The aerial parts of Stachys laxa Boiss. and Buhse. from Siah-bishe in Mazandaran province, Stachys trinervis Aitch. and Hemsl. from Karaj in Alborz province, Stachys subaphylla Rech. F. and Stachys turcomanica Trautv. from Golestan province have been collected in May 2008. Total extracts were obtained through MeOH/H2O (80/20) and then partitioned between CHCl3, EtOAc and MeOH. These fractions and total extracts have been investigated for in-vitro cytotoxic activity against the colon carcinoma (HT-29), colorectal adenocarcinoma (Caco-2), breast ductal carcinoma (T47D) and Swiss mouse embryo fibroblast (NIH 3T3) cell lines using MTT assay (3-(4,5-di methyl thiazol-2-yl)-2,5-di phenyltetrazolium bromide). At each cell line, doses of 3.125, 6.25, 12.5, 25, 100, 200, 400 and 800 µg/mL in 1% (v/v) DMSO of all samples were tested. Ethyl acetate and chloroform fractions of Stachys laxa against proliferation of T47D and HT-29 cell lines and chloroform fraction of Stachys subaphylla and Stachys subaphylla ethyl acetate fraction toward T47D cell line exhibited highest cytotoxic activity (IC50 < 50 µg/mL). Ethyl acetate and chloroform fractions of Stachys turcomanica against HT-29 cell line, except methanol fraction of Stachys subaphylla, the other extrcts on T47D cell line, represented moderate cytotoxic activity (IC50 < 70 µg/mL). All fractions of S. trinervis demonstrated no effective cytotoxic activity. IC50 values confirmed that the growth and proliferation of HT-29 and T47D cells were most affected by chloroform and ethyl acetate fractions of Stachys laxa and Stachys turcomanica due to their nonpolar compounds. PMID:24250483

  13. Supercritical CO2 extraction of functional compounds from Spirulina and their biological activity.

    PubMed

    K G, Mallikarjun Gouda; K, Udaya Sankar; R, Sarada; G A, Ravishankar

    2015-06-01

    Supercritical carbon dioxide (SCCO2) extraction and fractionation of Spirulina platensis was carried out to obtain functional compounds with antioxidant, antimicrobial and enzyme inhibitory activities. Extraction of SCCO2 was carried out using 200 g of Spirulina powder at 40 ºC under 120 bar pressure with CO2 flow rate of 1.2 kg h(-1). SCCO2 fraction obtained was further treated with hexane and ethyl acetate to identify its components. Individual components were identified by comparing mass spectra of samples with standard data and retention indices (RI) of C5-C20 n-alkanes mixture using the kovat index formula. The phenolic and flavonoid content of the SCCO2 extract was found to be 0.34 ± 0.01 g/100 g and 0.12 ± 0.01 g/100 g respectively. The SCCO2 extract had antioxidant activity with IC50 value of 109.6 ± 3.0 μg mL(-1) for DPPH (2,2-Diphenyl-1-picryl hydrazyl radical), IC50 value of 81.66 ± 2.5 μg mL(-1) for reducing power and IC50 value of 112.70 ± 0.8 μg mL(-1) for hydroxyl radical scavenging activity. Further, antioxidant activity study on oxidative induced DNA damage was analysed to elucidate the positive role of SCCO2 extract. SCCO2 extracts showed high antimicrobial activity against Gram-positive bacteria (Staphylococcus aureus FRI 722 and Bacillus cereus F 4810) compared to that of Gram negative bacteria (Escherichia coli MTCC 108 and Yersinia enterocolitica MTCC 859). The SCCO2 extract exhibited inhibitory activity on both Angiotensin-1 converting enzyme and α-glucosidase with IC50 values of 274 ± 1.0 μg mL(-1) and 307 ± 2.0 μg mL(-1) respectively. PMID:26028745

  14. Antileishmanial Activity and Structure-Activity Relationship of Triazolic Compounds Derived from the Neolignans Grandisin, Veraguensin, and Machilin G.

    PubMed

    Costa, Eduarda C; Cassamale, Tatiana B; Carvalho, Diego B; Bosquiroli, Lauriane S S; Ojeda, Mariáh; Ximenes, Thalita V; Matos, Maria F C; Kadri, Mônica C T; Baroni, Adriano C M; Arruda, Carla C P

    2016-01-01

    Sixteen 1,4-diaryl-1,2,3-triazole compounds 4-19 derived from the tetrahydrofuran neolignans veraguensin 1, grandisin 2, and machilin G 3 were tested against Leishmania (Leishmania) amazonensis intracellular amastigotes. Triazole compounds 4-19 were synthetized via Click Chemistry strategy by 1,3-dipolar cycloaddition between terminal acetylenes and aryl azides containing methoxy and methylenedioxy groups as substituents. Our results suggest that most derivatives were active against intracellular amastigotes, with IC50 values ranging from 4.4 to 32.7 µM. The index of molecular hydrophobicity (ClogP) ranged from 2.8 to 3.4, reflecting a lipophilicity/hydrosolubility rate suitable for transport across membranes, which may have resulted in the potent antileishmanial activity observed. Regarding structure-activity relationship (SAR), compounds 14 and 19, containing a trimethoxy group, were the most active (IC50 values of 5.6 and 4.4 µM, respectively), with low cytotoxicity on mammalian cells (SI = 14.1 and 10.6). These compounds induced nitric oxide production by the host macrophage cells, which could be suggested as the mechanism involved in the intracellular killing of parasites. These results would be useful for the planning of new derivatives with higher antileishmanial activities. PMID:27331807

  15. Modulatory role of a constitutively active population of alpha(1D)-adrenoceptors in conductance arteries.

    PubMed

    Ziani, Khalid; Gisbert, Regina; Noguera, Maria Antonia; Ivorra, Maria Dolores; D'Ocon, Pilar

    2002-02-01

    A constitutively active population of alpha(1D)-adrenoceptors in iliac and proximal, distal, and small mesenteric rat arteries was studied. The increase in resting tone (IRT) that evidences it was observed only in iliac and proximal mesenteric and was inhibited by prazosin (pIC(50) = 9.57), 5-methylurapidil (pIC(50) = 7.61), and BMY 7378 (pIC(50) = 8.77). Chloroethylchlonidine (100 micromol/l) did not affect IRT, but when added before the other antagonists it blocked their effect. The potency shown by BMY 7378 confirms the alpha(1D)-subtype as responsible for IRT. BMY 7378 displayed greater inhibition of adrenergic responses in iliac (pIC(50) = 7.57 +/- 0.11) and proximal mesenteric arteries (pIC(50) = 8.05 +/- 0.2) than in distal (pIC(50) = 6.94 +/- 0.13) or small mesenteric arteries (pIC(50) = 6.30 +/- 0.14), which confirms the functional role of the alpha(1D)-adrenoceptor in iliac and proximal mesenteric arteries. This subtype prevents abrupt changes in iliac and proximal mesenteric artery caliber when the agonist disappears, and this modulatory role is evidenced by the slower decay in the response to norepinephrine after removal. PMID:11788394

  16. Investigations into the antiadhesive activity of herbal extracts against Campylobacter jejuni.

    PubMed

    Bensch, K; Tiralongo, J; Schmidt, K; Matthias, A; Bone, K M; Lehmann, R; Tiralongo, E

    2011-08-01

    Campylobacter jejuni is one of the most common bacterial causes of diarrhoea in the industrialized world, being associated with the occurrence of Guillain-Barré Syndrome, and inducing diseases partially through intestinal adherence. With increasing reports of C. jejuni drug resistance against standard antibiotics, investigations into antiadhesive agents for the prevention of bacterial infection are highly significant. Given the consumer-driven development towards holistic and integrative healthcare, research into additional anti-Campylobacter effects of herbal medicines that are already used for their beneficial effects on bowel and digestive functions is important. Twenty-one herbal extracts were screened for antiadhesive activity against C. jejuni using modifications of previously published antiadhesion assays. Antiadhesion effects with IC(50) values <3 mg/mL were obtained for seven ethanol plant extracts, with Zingiber officinale (ginger), Capsicum annum (cayenne) and Glycyrrhiza glabra (licorice) displaying the highest antiadhesion activity against C. jejuni (IC(50) : <0.1 mg/mL, 0.29 mg/mL and 0.65 mg/mL, respectively). Differences in antiadhesion activity were found for two different Echinacea species, with E. purpurea displaying significantly higher and dose dependent antiadhesion activity than E. angustifolia. No significant antiadhesion activity (IC(50) values >35 mg/mL) was found for Agrimonia eupatoria (agrimony), Andrographis paniculata (andrographis), Matricaria recutita (chamomile), Foeniculum vulgare (fennel), Filipendula ulmaria (meadowsweet) and Artemisia absinthium (wormwood) extracts. This study provides evidence for additional beneficial effects of marketed herbal medicines in gastrointestinal disorders. PMID:21280113

  17. Effects of methoxychlor and 2,2-bis ( p -hydroxyphenyl)-1,1,1-trichloroethane on cytochrome P450 enzyme activities in human and rat livers.

    PubMed

    Chen, Bingbing; Pan, Peipei; Wang, Li; Chen, Menchun; Dong, Yaoyao; Ge, Ren-Shan; Hu, Guo-Xin

    2015-01-01

    Cytochrome P450 (CYP) enzymes are involved in the metabolism of endogenous and exogenous compounds. Human and rat liver microsomes were used to investigate the inhibitory effects of methoxychlor (MXC) and its metabolite 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) on the activities of corresponding human and rat CYPs. Probe drugs were used to test the inhibitory effects of MXC and HPTE on human and rat CYPs. The results showed that MXC and HPTE inhibited both human CYP2C9 and rat liver CYP2C11 activity, with half-maximal inhibitory concentration (IC50) values of 15.47 ± 0.36 (MXC) and 8.87 ± 0.53 μmol/l (HPTE) for human CYP2C9, and of 22.45 ± 1.48 (MXC) and 24.63 ± 1.35 μmol/l (HPTE) for rat CYP2C11. MXC and HPTE had no effects on human CYP2C19 activity but inhibited rat CYP2C6 activity with IC50 values of 14.84 ± 0.04 (MXC) and 8.72 ± 0.25 μmol/l (HPTE). With regard to human CYP2D6 and rat CYP2D2 activity, only HPTE potently inhibited human CYP2D6 activity, with an IC50 value of 16.56 ± 0.69 μmol/l. Both chemicals had no effect on human CYP3A4 and rat CYP3A1 activity. In summary, MXC and HPTE are potent inhibitors of some human and rat CYPs. PMID:25833162

  18. Flavonoids and its derivatives from Callistephus chinensis flowers and their inhibitory activities against alpha-glucosidase

    PubMed Central

    Zhang, Xiaoshu; Liu, Zhenting; Bi, Xiuli; Liu, Jingxin; Li, Wei; Zhao, Yuqing

    2013-01-01

    Inhibitors of carbohydrate-hydrolysing enzymes play an important role for the treatment of diabetes. One of the therapeutic methods for decreasing of postprandial hyperglycemia is to retard absorption of glucose by the inhibition of carbohydrate- hydrolysing enzymes, such as α-glucosidase, in the digestive organs. To investigate the therapeutic potential of compounds from natural sources, Callistephus chinensis flowers (CCF) were tested for inhibition of α-glucosidase, and acarboes was used as the positive control. The 70 % ethanol extract of CCF exhibited significant α-glucosidase inhibitory activities with IC50 value of 8.14 μg/ml. The stepwise polarity fractions of CCF were tested further for in vitro inhibition of α-glucosidase. The ethyl acetate (EtOAc) fraction exhibited the most significant inhibitory activity. Eight pure compounds, apigenin, apigenin-7-O-β-D- glucoside, kaempferol, hyperin, naringenin, quercetin, luteolin, and kaempferol-7-O-β-D- glucoside, were isolated (using enzyme assay-guide fractionation method) from the EtOAc fraction. Among these, quercetin was the most active one (IC50 values 2.04 μg/ml), and it appears that the inhibiting percentages are close to acarbose (IC50 values 2.24 μg/ml), the positive control, on α-glucosidase inhibition. HPLC/UV analysis indicated that the major components of CCF are kaempferol, hyperin and quercetin. The presented results revealed that CCF containing these eight flavonoids could be a useful natural source in the development of a novel α-glucosidase inhibitory agent against diabetic complications. PMID:27298611

  19. Antioxidant and Cytotoxic Activities and Phytochemical Analysis of Euphorbia wallichii Root Extract and its Fractions

    PubMed Central

    Ul-Haq, Ihsan; Ullah, Nazif; Bibi, Gulnaz; Kanwal, Simab; Sheeraz Ahmad, Muhammad; Mirza, Bushra

    2012-01-01

    Euphorbia wallichii a perennial herb growing mainly in Himalayas has been widely used in folk medicines for its medicinal properties. In the present study, the crude methanolic root extract (CME) and its fractions; n-Hexane Fraction (NHF), n-Butanol Fraction (NBF), Chloroform Fraction (CHF), Ethyl acetate Fraction (EAF) and Aqueous Fraction (AQF) of this plant specie were investigated for antioxidant and cytotoxic activities and phytochemical analysis. Antioxidant activity was determined by using 2,2-diphenyl-1-picryl-hydrazyl free radical (DPPH) and DNA protection assay performed on pBR322 plasmid DNA. In both these assays, promising results were obtained for CME as well as other fractions. The IC50 values for DPPH assay were in a range of 7.89 to 63.35 μg/ml in which EAF showed the best anti-oxidant potential and almost all the tested samples showed certain level of DNA protection. The cytotoxic activity was assessed by using Sulforhodamine B (SRB) assay on human cell lines; H157 (Lung Carcinoma) and HT144 (Malignant Melanoma). The IC50 values of the tested samples ranged from 0.18 to 1.4 mg/mL against H157 cell line whereas against HT144 cell line the IC50 values ranged from 0.46 to 17.88 mg/mL with NBF fraction showing maximum potential for both. Furthermore, the phytochemical analysis of CME and its fractions showed the presences of flavonoids, saponins, tannins, terpenoides and cardiac glycosides with varying concentrations. PMID:24250446

  20. 3-[(6-Arylamino)pyridazinylamino]benzoic acids: design, synthesis and in vitro evaluation of anticancer activity.

    PubMed

    Abouzid, Khaled A M; Khalil, Nadia A; Ahmed, Eman M; Mohamed, Khaled Omar

    2013-01-01

    A series of novel substituted 3,6-disubstituted pyridazines based on the structure of vatalanib (PTK787) were designed and synthesized. The cytotoxicity of the final compounds was tested in vitro on HT-29 colon cancer cell line. Compounds 2a and 2b with 4-chlorophenylamino moiety, exerted the highest cytotoxic activity with IC(50) values equal to 15.3 and 3.9 μM respectively. The most promising compound, 2b, was found to be about fivefold more active than vatalanib against HT-29 colon cancer cell line. PMID:23307426

  1. Synthesis and biological evaluation of open-chain analogs of cyclic peptides as inhibitors of cellular Shp2 activity.

    PubMed

    Zhen, Xiao-Li; Yin, Wen-Hui; Tian, Xia; Ma, Zhen-Jie; Fan, Shi-Ming; Han, Jian-Rong; Liu, Shouxin

    2015-05-15

    A series of open-chain analogs of cyclic peptides was designed and synthesized using sansalvamide A as a model compound. All compounds exhibited low antitumor activity. Furthermore, the evaluation of their inhibitory potency toward IMPDH, SHP2, ACHE, proteasome, MAGL, and cathepsin B showed that all of the compounds were potent against protein tyrosine phosphatase Shp2. Specifically, compounds 1a, 1d, 2b, and 2f were found to inhibit SHP2 with IC50 values in the low micromolar range and good selectivity. Based on the molecular docking results, the binding modes of the chain cyclic peptides in the active center of SHP2 were discussed. PMID:25865131

  2. Identification of a novel boronic acid as a potent, selective, and orally active hormone sensitive lipase inhibitor.

    PubMed

    Ogiyama, Tomoko; Yamaguchi, Mitsuhiro; Kurikawa, Nobuya; Honzumi, Shoko; Yamamoto, Yuka; Sugiyama, Daisuke; Inoue, Shinichi

    2016-08-15

    Hormone sensitive lipase (HSL) is an attractive therapeutic target of dyslipidemia. We designed and synthesized several compounds as reversible HSL inhibitors with a focus on hydrophobic interactions, which was thought to be effective upon the HSL inhibitory activity. In these efforts, we identified boronated compound 12 showing a potent HSL inhibitory activity with an IC50 value of 7nM and a high selectivity against cholinesterases. Furthermore, compound 12 is the first boron containing HSL inhibitor that has shown an antilipolytic effect in rats after oral administration at 3mg/kg. PMID:27338659

  3. Evaluation of Antioxidant, Free Radical Scavenging, and Antimicrobial Activity of Quercus incana Roxb.

    PubMed Central

    Sarwar, Rizwana; Farooq, Umar; Khan, Ajmal; Naz, Sadia; Khan, Sara; Khan, Afsar; Rauf, Abdur; Bahadar, Haji; Uddin, Reaz

    2015-01-01

    Considering the indigenous utilization of Quercus incana Roxb., the present study deals with the investigation of antioxidant, free radical scavenging activity, total phenolic content, and antimicrobial activity of Q. incana Roxb. In vitro antioxidant activity of the plant fractions were determined by 1,1-diphenyl-2-picrylhydrazyl and nitric oxide scavenging method. Total phenolic contents were determined by gallic acid equivalent and antimicrobial activities were determined by agar well diffusion method. It was observed that Q. incana Roxb. showed significant antibacterial activity against Gram-positive and Gram-negative bacteria. n-Butanol fraction showed maximum activity against Micrococcus leuteus with 19 mm zone of inhibition. n-Butanol fraction of Q. incana Roxb. showed immense antifungal activity against Aspergillus niger (32 mm ± 0.55) and A. flavus (28 mm ± 0.45). Similarly n-butanol fraction showed relatively good antioxidant activity with IC50 value of 55.4 ± 0.21 μg/mL. The NO scavenging activity of ethyl acetate fraction (IC50 = 23.21 ± 0.31 μg/mL) was fairly good compared to other fractions. The current study of Q. incana Roxb. suggests the presences of synergetic action of some biological active compounds that may be present in the leaves of medicinal plant. Further studies are needed to better characterize the important active constituents responsible for the antimicrobial, antioxidant and free radical scavenging activity. PMID:26635607

  4. An active inference and epistemic value view of metacognition.

    PubMed

    Moulin, Chris; Souchay, Celine

    2015-01-01

    Metacognition concerns our monitoring and control of mental operations (knowing what you know). Much thinking about metacognition is liable to fall foul of the classic homunculus problem: Nobody can specify who or what does the "metacognition." We describe how the Active Inference and Epistemic Value (AIEV) model offers an operationalization of epistemic behaviors which can explain two example metacognitive phenomena: Control and monitoring of word learning, and the search for unretrieved information in the feeling of knowing. Curiosity drives a search forward, but it is held in check by considering the utility of what is retrieved from memory. PMID:25977988

  5. Antimicrobial and antioxidant activity of kaempferol rhamnoside derivatives from Bryophyllum pinnatum

    PubMed Central

    2012-01-01

    Background Bryophyllum pinnatum (Lank.) Oken (Crassulaceae) is a perennial succulent herb widely used in traditional medicine to treat many ailments. Its wide range of uses in folk medicine justifies its being called "life plant" or "resurrection plant", prompting researchers' interest. We describe here the isolation and structure elucidation of antimicrobial and/or antioxidant components from the EtOAc extract of B. pinnatum. Results The methanol extract displayed both antimicrobial activities with minimum inhibitory concentration (MIC) values ranging from 32 to 512 μg/ml and antioxidant property with an IC50 value of 52.48 μg/ml. Its partition enhanced the antimicrobial activity in EtOAc extract (MIC = 16-128 μg/ml) and reduced it in hexane extract (MIC = 256-1024 μg/ml). In addition, this process reduced the antioxidant activity in EtOAc and hexane extracts with IC50 values of 78.11 and 90.04 μg/ml respectively. Fractionation of EtOAc extract gave seven kaempferol rhamnosides, including; kaempferitrin (1), kaempferol 3-O-α-L-(2-acetyl)rhamnopyranoside-7-O-α-L-rhamnopyranoside (2), kaempferol 3-O-α-L-(3-acetyl)rhamnopyranoside-7-O-α-L-rhamnopyranoside (3), kaempferol 3-O-α-L-(4-acetyl)rhamnopyranoside-7-O-α-L-rhamnopyranoside (4), kaempferol 3-O-α-D- glucopyranoside-7-O-α-L-rhamnopyranoside (5), afzelin (6) and α-rhamnoisorobin (7). All these compounds, except 6 were isolated from this plant for the first time. Compound 7 was the most active, with MIC values ranging from 1 to 2 μg/ml and its antioxidant activity (IC50 = 0.71 μg/ml) was higher than that of the reference drug (IC50 = 0.96 μg/ml). Conclusion These findings demonstrate that Bryophyllum pinnatum and some of its isolated compounds have interesting antimicrobial and antioxidant properties, and therefore confirming the traditional use of B. pinnatum in the treatment of infectious and free radical damages. PMID:22433844

  6. Synthesis and cytotoxic activities of E-resveratrol derivatives.

    PubMed

    Hong, Ting; Jiang, Wei; Dong, Huai-Ming; Qiu, Sheng-Xiang; Lu, Yu

    2015-05-01

    The present study was designed to synthesize derivatives of E-resveratrol and evaluate their cytotoxic activity in vitro. Different functional groups were conjugated with the phenolic hydroxyl group of E-resveratrol, and the double bond of E-resveratrol was reduced. The in vitro cytotoxicity of the synthetic derivatives was evaluated against three tumor cell lines (A549, LAC, and HeLa) using the MTT assay. Twenty-six E-resveratrol derivatives were synthesized and their structures were confirmed by (1)H NMR, MS, IR, and elemental analyses. Compounds 1-6, 12, 15-21, and 23-26 were reported for the first time. Among them, Compounds 1, 2, 4, 5, and 9-11, showed significant cytotoxicity against tumor cells; especially, Compound 1 showed an IC50 value of 4.38 μmol · L(-1) in the A549 cells which was 15-fold more active than E-resveratrol; Compound 9 showed an IC50 value of 1.41 μmol · L(-1) in the HeLa cell line which was 90-fold more active than E-resveratrol, and close to adriamycin. The structure-activity relationships were also investigated. Compounds 1, 2 and 9-11 may serve as potential lead compounds for the discovery of new anticancer drugs. PMID:25986287

  7. Antichagasic and trichomonacidal activity of 1-substituted 2-benzyl-5-nitroindazolin-3-ones and 3-alkoxy-2-benzyl-5-nitro-2H-indazoles.

    PubMed

    Fonseca-Berzal, Cristina; Ibáñez-Escribano, Alexandra; Reviriego, Felipe; Cumella, José; Morales, Paula; Jagerovic, Nadine; Nogal-Ruiz, Juan José; Escario, José Antonio; da Silva, Patricia Bernardino; Soeiro, Maria de Nazaré C; Gómez-Barrio, Alicia; Arán, Vicente J

    2016-06-10

    Two series of new 5-nitroindazole derivatives, 1-substituted 2-benzylindazolin-3-ones (6-29, series A) and 3-alkoxy-2-benzyl-2H-indazoles (30-37, series B), containing differently functionalized chains at position 1 and 3, respectively, have been synthesized starting from 2-benzyl-5-nitroindazolin-3-one 5, and evaluated against the protozoan parasites Trypanosoma cruzi and Trichomonas vaginalis, etiological agents of Chagas disease and trichomonosis, respectively. Many indazolinones of series A were efficient against different morphological forms of T. cruzi CL Brener strain (compounds 6, 7, 9, 10 and 19-21: IC50 = 1.58-4.19 μM for epimastigotes; compounds 6, 19-21 and 24: IC50 = 0.22-0.54 μM for amastigotes) being as potent as the reference drug benznidazole. SAR analysis suggests that electron-donating groups at position 1 of indazolinone ring are associated with an improved antichagasic activity. Moreover, compounds of series A displayed low unspecific toxicities against an in vitro model of mammalian cells (fibroblasts), which were reflected in high values of the selectivity indexes (SI). Compound 20 was also very efficient against amastigotes from Tulahuen and Y strains of T. cruzi (IC50 = 0.81 and 0.60 μM, respectively), showing low toxicity towards cardiac cells (LC50 > 100 μM). In what concerns compounds of series B, some of them displayed moderate activity against trophozoites of a metronidazole-sensitive isolate of T. vaginalis (35 and 36: IC50 = 9.82 and 7.25 μM, respectively), with low unspecific toxicity towards Vero cells. Compound 36 was also active against a metronidazole-resistant isolate (IC50 = 9.11 μM) and can thus be considered a good prototype for the development of drugs directed to T. vaginalis resistant to 5-nitroimidazoles. PMID:27017556

  8. Antiplatelet aggregation and platelet activating factor (PAF) receptor antagonistic activities of the essential oils of five Goniothalamus species.

    PubMed

    Moharam, Bushra Abdulkarim; Jantan, Ibrahim; Ahmad, Fasihuddin bin; Jalil, Juriyati

    2010-08-01

    Nine essential oils, hydrodistilled from different parts of five Goniothalamus species (G. velutinus Airy-Shaw, G. woodii Merr., G. clemensii Ban, G. tapis Miq. and G. tapisoides Mat Salleh) were evaluated for their ability to inhibit platelet aggregation in human whole blood using an electrical impedance method and their inhibitory effects on platelet activating factor (PAF) receptor binding with rabbit platelets using 3H-PAF as a ligand. The chemical composition of the oils was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The bark oil of G. velutinus was the most effective sample as it inhibited both arachidonic acid (AA) and ADP-induced platelet aggregation with IC(50) values of 93.6 and 87.7 microg/mL, respectively. Among the studied oils, the bark oils of G. clemensii, G. woodii, G. velutinus and the root oil of G. tapis showed significant inhibitory effects on PAF receptor binding, with IC(50 )values ranging from 3.5 to 10.5 microg/mL. The strong PAF antagonistic activity of the active oils is related to their high contents of sesquiterpenes and sesquiterpenoids, and the individual components in the oils could possibly produce a synergistic effect in the overall antiplatelet activity of the oils. PMID:20714290

  9. In vitro antimalarial activity of different extracts of Eremostachys macrophylla Montbr. & Auch.

    PubMed Central

    Asnaashari, Solmaz; Heshmati Afshar, Fariba; Ebrahimi, Atefeh; Bamdad Moghadam, Sedigheh; Delazar, Abbas

    2015-01-01

    Introduction:The risk of drug resistance and the use of medicinal plants in malaria prevention and treatment have led to the search for new antimalarial compounds with natural origin. Methods:In the current study, six extracts with different polarity from aerial parts and rhizomes of Eremostachys macrophylla Montbr. & Auch., were screened for their antimalarial properties by cell-free β-hematin formation assay. Results: Dichloromethane (DCM) extracts of both parts of plant showed significant antimalarial activities with IC50 values of 0.797 ± 0.016 mg/mL in aerial parts and 0.324 ± 0.039 mg/mL in rhizomes compared to positive control (Chloroquine, IC50 = 0.014 ± 0.003 mg/mL, IC90 = 0.163 ± 0.004 mg/mL). Bioactivity-guided fractionation of the most potent part (DCM extract of rhizomes) by vacuum liquid chromatography (VLC) afforded seven fractions. Sixty percent ethyl acetate/n-hexane fraction showed considerable antimalarial activity with IC50 value of 0.047 ± 0.0003 mg/mL. Conclusion: From 6 extracts with different polarity of E. macrophylla,s aerial parts and rhizomes, the DCM extract of both parts were the most active extract in this assay. The preliminary phytochemical study on the VLC fractions of the most potent part persuades us to focus on purifying the active components of these extracts and to conduct further investigation towards in vivo evaluation. PMID:26457251

  10. Design, synthesis, in-vitro antiproliferative activity and kinase profile of new picolinamide based 2-amido and ureido quinoline derivatives.

    PubMed

    El-Damasy, Ashraf Kareem; Seo, Seon Hee; Cho, Nam-Chul; Kang, Soon Bang; Pae, Ae Nim; Kim, Key-Sun; Keum, Gyochang

    2015-08-28

    New 2-amido and ureido quinoline derivatives substituted with 2-N-methylamido-pyridin-4-yloxy group at the 5-position of quinoline (18 final compounds) have been designed and synthesized as anticancer sorafenib congeners. Among the synthesized derivatives, fourteen compounds were selected for evaluation of their antiproliferative activity over a panel of 60 cancer cell lines at a single dose concentration of 10 μM at National Cancer Institute (NCI, USA). Four compounds, 9b-d and 9f showed promising mean growth inhibitions and thus were further tested at five-dose testing mode to determine their IC50 values. The data revealed that 2,4-difluorophenyl (9b) and 4-chloro-3-trifluoromethylphenyl (9d) urea compounds are the most active derivatives with significant efficacies and superior potencies than sorafenib in 36 and 12 cancer cell lines, respectively, belonging particularly to renal carcinoma cell (RCC), ovarian, and non small cell lung cancer (NSCL). Compound 9b and 9d were found to be six and two times more potent than sorafenib against A498 RCC line, with IC50 values of 0.42 μM and 1.36 μM, respectively. Accordingly, compound 9d was screened over a panel of 41 oncogenic kinases at a single dose concentration of 10 μM to profile its kinase inhibitory activity. Interestingly, the compound showed highly selective inhibitory activities ( 81.8% and 96.3%) against BRAF(V600E) and C-RAF kinases with IC50 values of 316 nM and 61 nM, respectively. In addition, molecular docking, cell cycle analysis, compliance to Lipinski's rule of five, and in silico toxicity assessment have been reported. PMID:26218653

  11. (+)-Chenabinol (Revised NMR Data) and Two New Alkaloids from Berberis vulgaris and their Biological Activity.

    PubMed

    Novák, Zdenĕk; Hošt'álková, Anna; Opletal, Lubomír; Nováková, Lucie; Hrabinová, Martina; Kuneš, Jiří; Cahlíková, Lucie

    2015-10-01

    A known alkaloid (+)-chenabinol (1) and two new secobisbenzylisoquinoline alkaloids were isolated by standard chromatographic methods from the root bark of Berberis vulgaris L. The structures of the new alkaloids, named berkristine (2) and verfilline (3), were established by spectroscopic (including 2D NMR), and HRMS (ESI) methods. The alkaloids were tested for their inhibition activity of human cholinesterases and prolyl oligopeptidase. Compound 1 inhibited human butyrylcholinesterase with an IC50 value of 44.8 ± 5.4 μM. PMID:26669104

  12. Nitrogen-containing bibenzyls from Pleione bulbocodioides: absolute configurations and biological activities.

    PubMed

    Li, Yuan; Zhang, Fan; Wu, Ze-Hong; Zeng, Ke-Wu; Zhang, Chen; Jin, Hong-Wei; Zhao, Ming-Bo; Jiang, Yong; Li, Jun; Tu, Peng-Fei

    2015-04-01

    Four new pyrrolidone substituted bibenzyls, dusuanlansins A-D (1-4) were isolated from the pseudo bulbs of Pleione bulbocodioides, along with 19 known compounds (5-23). Compounds 1-4 are two pairs of epimers of pyrrolidone substituted bibenzyls, which were separated successfully by a Chiralcel OD-RH C18 column. Their absolute configurations were elucidated by calculated ECD. Biological investigations showed that compounds 5 and 7 exhibited potent anti-inflammatory activities on LPS-stimulated NO production in BV-2 microglial cells, with IC50 values of 2.46 and 3.14μM, respectively. PMID:25647325

  13. Flavonol dimers from callus cultures of Dysosma versipellis and their in vitro neuraminidase inhibitory activities.

    PubMed

    Chen, Ridao; Duan, Ruigang; Wei, Yannan; Zou, Jianhua; Li, Junwei; Liu, Xiaoyue; Wang, Haiyan; Guo, Ying; Li, Qiuhong; Dai, Jungui

    2015-12-01

    A chemical investigation of callus cultures of Dysosma versipellis led to the isolation of five new flavonol dimers, dysoverines A-E (1-5), together with 12 known compounds (6-17). The structures of new compounds were determined by the extensive spectroscopic data analyses. The biosynthetic pathway of the new compounds was proposed to involve O-methylation, prenylation, and Diels-Alder cycloaddition, which successively occurred in cultured plant cells. Compounds 1-17 exhibited in vitro neuraminidase inhibitory activities with the IC50 values of 31.0-93.9μM. PMID:26481138

  14. Blumeaenes A-J, sesquiterpenoid esters from Blumea balsamifera with NO inhibitory activity.

    PubMed

    Chen, Ming; Qin, Jiang-Jiang; Fu, Jian-Jun; Hu, Xiao-Jia; Liu, Xiao-Hua; Zhang, Wei-Dong; Jin, Hui-Zi

    2010-06-01

    Chemical examination of the ethanol extract of the aerial parts of Blumea balsamifera led to the isolation of ten new sesquiterpenoid esters, blumeaenes A-J (1- 10), with 13 known flavonoids. Their structures were determined mainly by use of 1D and 2D NMR spectroscopic techniques. All sesquiterpenoid esters were tested for their inhibitory activity against LPS-induced NO production in RAW264.7 macrophages. Compounds 1, 4 and 5 showed slight inhibitory effect on the production of NO with IC(50) values of 40.06, 46.35 and 57.80 microg/mL, respectively. PMID:20101563

  15. Eudesmane-type sesquiterpenoids from Salvia plebeia inhibit IL-6-induced STAT3 activation.

    PubMed

    Jang, Hyun-Jae; Oh, Hyun-Mee; Hwang, Joo Tae; Kim, Mi-Hwa; Lee, Soyoung; Jung, Kyungsook; Kim, Young-Ho; Lee, Seung Woong; Rho, Mun-Chual

    2016-10-01

    Seven eudesmane-type sesquiterpenoid lactones and the known plebeiolide C were isolated from an ethanol-soluble extract of the aerial parts of Salvia plebeia R. Br. Their structures were determined via NMR and MS, and their absolute configurations were elucidated using ECD, and X-ray crystallographic analysis, as well as the modified Mosher ester method. All isolates were evaluated for their inhibitory effects on IL6-induced STAT3 promoter activation in stably transfected Hep3B cells. Of these isolates, eudebeiolide D exhibited an inhibitory effect with the IC50 value of 1.1 μM. PMID:27506573

  16. Four New Flavonoids with α-Glucosidase Inhibitory Activities from Morus alba var. tatarica.

    PubMed

    Zhang, Ya-Long; Luo, Jian-Guang; Wan, Chuan-Xing; Zhou, Zhong-Bo; Kong, Ling-Yi

    2015-11-01

    Four new flavonoids, mortatarins A-D (1-4, resp.), along with eight known flavonoids (5-12) were isolated from the root bark of Morus alba var. tatarica. Their structures were established on the basis of spectroscopic data analysis, and the absolute configuration of 4 was determined by analysis of its CD spectrum. All isolates were tested for inhibitory activities against α-glucosidase. Compounds 4, 7, and 8 exhibited a significant degree of inhibition with IC50 values of 5.0 ± 0.3, 7.5 ± 0.5, and 5.9 ± 0.2 μM, respectively. PMID:26567954

  17. Activity Prediction and Molecular Mechanism of Bovine Blood Derived Angiotensin I-Converting Enzyme Inhibitory Peptides

    PubMed Central

    Zhang, Ting; Nie, Shaoping; Liu, Boqun; Yu, Yiding; Zhang, Yan; Liu, Jingbo

    2015-01-01

    Development of angiotensin I-converting enzyme (ACE, EC 3.4.15.1) inhibitory peptides from food protein is under extensive research as alternative for the prevention of hypertension. However, it is difficult to identify peptides released from food sources. To accelerate the progress of peptide identification, a three layer back propagation neural network model was established to predict the ACE-inhibitory activity of pentapeptides derived from bovine hemoglobin by simulated enzyme digestion. The pentapeptide WTQRF has the best predicted value with experimental IC50 23.93 μM. The potential molecular mechanism of the WTQRF / ACE interaction was investigated by flexible docking. PMID:25768442

  18. Assessment of dual life stage antiplasmodial activity of british seaweeds.

    PubMed

    Spavieri, Jasmine; Allmendinger, Andrea; Kaiser, Marcel; Itoe, Maurice Ayamba; Blunden, Gerald; Mota, Maria M; Tasdemir, Deniz

    2013-10-01

    Terrestrial plants have proven to be a prolific producer of clinically effective antimalarial drugs, but the antimalarial potential of seaweeds has been little explored. The main aim of this study was to assess the in vitro chemotherapeutical and prophylactic potential of the extracts of twenty-three seaweeds collected from the south coast of England against blood stage (BS) and liver stage (LS) Plasmodium parasites. The majority (14) of the extracts were active against BS of P. falciparum, with brown seaweeds Cystoseira tamariscifolia, C. baccata and the green seaweed Ulva lactuca being the most active (IC(50)s around 3 μg/mL). The extracts generally had high selectivity indices (>10). Eight seaweed extracts inhibited the growth of LS parasites of P. berghei without any obvious effect on the viability of the human hepatoma (Huh7) cells, and the highest potential was exerted by U. lactuca and red seaweeds Ceramium virgatum and Halopitys incurvus (IC50 values 14.9 to 28.8 μg/mL). The LS-active extracts inhibited one or more key enzymes of the malarial type-II fatty acid biosynthesis (FAS-II) pathway, a drug target specific for LS. Except for the red seaweed Halopitys incurvus, all LS-active extracts showed dual activity versus both malarial intracellular stage parasites. This is the first report of LS antiplasmodial activity and dual stage inhibitory potential of seaweeds. PMID:24152562

  19. Assessment of Dual Life Stage Antiplasmodial Activity of British Seaweeds

    PubMed Central

    Spavieri, Jasmine; Allmendinger, Andrea; Kaiser, Marcel; Itoe, Maurice Ayamba; Blunden, Gerald; Mota, Maria M.; Tasdemir, Deniz

    2013-01-01

    Terrestrial plants have proven to be a prolific producer of clinically effective antimalarial drugs, but the antimalarial potential of seaweeds has been little explored. The main aim of this study was to assess the in vitro chemotherapeutical and prophylactic potential of the extracts of twenty-three seaweeds collected from the south coast of England against blood stage (BS) and liver stage (LS) Plasmodium parasites. The majority (14) of the extracts were active against BS of P. falciparum, with brown seaweeds Cystoseira tamariscifolia, C. baccata and the green seaweed Ulva lactuca being the most active (IC50s around 3 μg/mL). The extracts generally had high selectivity indices (>10). Eight seaweed extracts inhibited the growth of LS parasites of P. berghei without any obvious effect on the viability of the human hepatoma (Huh7) cells, and the highest potential was exerted by U. lactuca and red seaweeds Ceramium virgatum and Halopitys incurvus (IC50 values 14.9 to 28.8 μg/mL). The LS-active extracts inhibited one or more key enzymes of the malarial type-II fatty acid biosynthesis (FAS-II) pathway, a drug target specific for LS. Except for the red seaweed Halopitys incurvus, all LS-active extracts showed dual activity versus both malarial intracellular stage parasites. This is the first report of LS antiplasmodial activity and dual stage inhibitory potential of seaweeds. PMID:24152562

  20. Pharmacological activities of cilantro's aliphatic aldehydes against Leishmania donovani.

    PubMed

    Donega, Mateus A; Mello, Simone C; Moraes, Rita M; Jain, Surendra K; Tekwani, Babu L; Cantrell, Charles L

    2014-12-01

    Leishmaniasis is a chronic infectious disease caused by different Leishmania species. Global occurrences of this disease are primarily limited to tropical and subtropical regions. Treatments are available; however, patients complain of side effects. Different species of plants have been screened as a potential source of new drugs against leishmaniasis. In this study, we investigated the antileishmanial activity of cilantro (Coriandrum sativum) essential oil and its main components: (E)-2-undecenal, (E)-2-decenal, (E)-2-dodecenal, decanal, dodecanal, and tetradecanal. The essential oil of C. sativum leaves inhibits growth of Leishmani donovani promastigotes in culture with an IC50 of 26.58 ± 6.11 µg/mL. The aliphatic aldehydes (E)-2-decenal (7.85 ± 0.28 µg/mL), (E)-2-undecenal (2.81 ± 0.21 µg/mL), and (E)-2-dodecenal (4.35 ± 0.15 µg/mL), all isolated from C. sativum essential oil, are effective inhibitors of in vitro cultures of L. donovani promastigotes. Aldehydes (E)-2-decenal, (E)-2-undecenal, and (E)-2-dodecenal were also evaluated against axenic amastigotes and IC50 values were determined to be 2.47 ± 0.25 µg/mL, 1.25 ± 0.11 µg/mL, and 4.78 ± 1.12 µg/mL, respectively. (E)-2-Undecenal and (E)-2-dodecenal demonstrated IC50 values of 5.65 ± 0.19 µg/mL and 9.60 ± 0.89 µg/mL, respectively, against macrophage amastigotes. These cilantro compounds showed no cytotoxicity against THP-1 macrophages. PMID:25340465

  1. In vitro antiprotozoal activities and cytotoxicity of some selected Cameroonian medicinal plants.

    PubMed

    Ndjakou Lenta, B; Vonthron-Sénécheau, C; Fongang Soh, R; Tantangmo, F; Ngouela, S; Kaiser, M; Tsamo, E; Anton, R; Weniger, B

    2007-04-20

    Eight extracts from seven selected Cameroonian medicinal plants, traditionally used to treat malaria and other protozoal diseases, were tested in vitro for their antiprotozoal activities against Plasmodium falciparum K1 chloroquine-resistant strain, Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei rhodesiense, protozoa responsible for malaria, visceral leishmaniasis, Chagas disease and African trypanosomiasis, respectively. The most active extract against Plasmodium falciparum K1 strain and Trypanosoma brucei rhodesiense was the methanolic extract of Albizia zygia (Fabaceae) stem bark with IC(50) values of 1.0 microg/ml and 0.2 microg/ml, respectively. Five extracts showed IC(50) values below 5mug/ml against Leishmania donovani, with the methanolic seed extract of Harungana madagascarensis showing the highest activity, but only the methanolic extract of Albizia zygia showed activity against Trypanosoma cruzi. Cytotoxicity and selectivity indexes were estimated for the most active extracts. The best ratio of cytotoxicity to antiplasmodial activity (SI(a)=14) was established for the methanolic leaf extract of Symphonia globulifera (Clusiaceae), while the methanolic stem bark extract of Albizia zygia showed the best ratio of cytotoxicity to antitrypanosomal activity (SI(b)=22.5). PMID:17141994

  2. Antiparasitic activity of plumericin & isoplumericin isolated from Plumeria bicolor against Leishmania donovani

    PubMed Central

    Sharma, Umakant; Singh, Dharmendra; Kumar, Parveen; Dobhal, M. P.; Singh, Sarman

    2011-01-01

    Background & objectives: The severe toxicity, exorbitant cost and emerging resistance of Leishmania species against most of the currently used drugs underscores the urgent need for the alternative drugs. The present study evaluates in vitro anti-leishmanial activity of Plumeria bicolor and its isolated compounds. Methods: The in vitro anti-parasitic activity of chloroform extract of Plumeria bicolor, plumericin and isoplumericin were tested alongwith appropriate controls against promastigote and amastigote forms of Leishmania donovani using 96 well microtiter plate. The concentration used for assessing the anti-leishmanial activity of extract of Plumeria bicolor and both isolated compounds were 100 μg/ml and 15 μM, respectively. The viability of the cells was assessed by MTT assay. The cytotoxicity of these compounds was performed against J774G8 murine macrophage cells lines at the concentration of 30 μM. Results: The Plumeria bicolor extract showed activity with the IC50 of 21±2.2 and 14±1.6 μg/ml against promastigote and amastigote forms of L. donovani, respectively. Plumericin consistently showed high activity with the IC50 of 3.17±0.12 and 1.41±0.03 μM whereas isoplumericin showed the IC50 of 7.2±0.08 μM and 4.1±0.02 μM against promastigote and amastigote forms, respectively. Cytotoxic effect of the chloroform extract of P. bicolor, plumericin and isoplumericin was evaluated in murine macrophage (J774G8) model with CC50 value of 75±5.3 μg/ml, 20.6±0.5 and 24±0.7 μM, respectively. Interpretation & conclusions: Our results indicated that plumericin showed more potent activity than isoplumericin and might be a promising anti-leishmanial agent against L. donovani. PMID:22199112

  3. Leishmanicidal, trypanocidal, and cytotoxic activities of endophytic fungi associated with bioactive plants in Brazil

    PubMed Central

    Rosa, Luiz H.; Gonçalves, Vívian N.; Caligiorne, Rachel B.; Alves, Tânia M. A.; Rabello, Ana; Sales, Policarbo A.; Romanha, Alvaro J.; Sobral, Marcos E. G.; Rosa, Carlos A.; Zani, Carlos L.

    2010-01-01

    One hundred and twenty-one isolates of endophytic fungi were recovered from leaves of the bioactive Brazilian plant species Ageratum myriadenia , Palicourea tetraphylla , Piptadenia adiantoides, and Trixis vauthieri. All fungal isolates were cultivated in liquid media and crude extracts were obtained with ethyl acetate. The crude extracts were tested in bioassay panels using Leishmania amazonensis , Trypanosoma cruzi, the enzyme trypanothione reductase (TryR) from Trypanosoma cruzi, and three human cancer cell lines. Thirty-three extracts (27.2%) exhibited at least one biological activity. Seventeen extracts (14%) were cytotoxic against one or more human cancer cell line with the IC50 values ranged of >0.2 to 25 µg/mL. Twenty-four extracts (19.8%) inhibited the activity of TryR, and three showed ability to inhibit the growth of T. cruzi above 60% and their IC50 values ranged among 1 to 10 µg/mL. Eleven extracts (9%) were able to inhibit the growth of L. amazonensis and showed with IC50 values ranged among 4.6 to 24.4 µg/mL. The endophytic fungi were identified as belonging to the genera Alternaria , Arthrinium , Cochliobolus , Colletotrichum , Penicillium , Fusarium, and Gibberella. An interesting result was obtained for the bioactive isolates UFMGCB 508, 537, 899 and 903, which were related to fungi associated with medicinal plants native to Asia, Australia, Africa, and Polynesia. These results indicate that bioactive plants living in Brazilian ecosystems are a potential host of endophytic fungi able to produce bioactive prototype molecules for drug development against neglected tropical diseases. PMID:24031513

  4. Synthesis and anti-DNA viral activities in vitro of certain 2,4-disubstituted-7-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)pyrrolo[2,3-d d pyrimidine nucleosides.

    PubMed

    Bhattacharya, B K; Ojwang, J O; Rando, R F; Huffman, J H; Revankar, G R

    1995-09-29

    Several novel 2,4-disubstituted-7-(2-deoxy-2-fluoro-beta-D- arabinofuranosyl)pyrrolo[2,3-d]pyrimidines have been synthesized and evaluated for their anti-human cytomegalovirus (HCMV), anti-hepatitis B virus (HBV), and anti-herpes simplex virus (HSV) activities in vitro. These nucleosides were prepared starting from 2-amino-4-chloro-7-(2-deoxy-2-fluoro- 3,5-di-O-benzoyl-beta-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine (3), which in turn was synthesized by direct glycosylation of the sodium salt of 2-amino-4-chloropyrrolo[2,3-d]pyrimidine (1) with 2-deoxy-2-fluoro-3,5-di-O-benzoyl-alpha-D-arabinofuranosyl bromide (2). Displacement of the 4-chloro group of 3 with OH, NH2, NHOH, SH, and SeH nucleophiles furnished the corresponding nucleosides 6-8, 12, and 14, respectively. The 3'-deoxygenation of 2-amino-4-chloro-7- (2-deoxy-2-fluoro-beta-D-arabinofuranosyl)pyrrolo[2,3-d]pyrimidine (4) and subsequent amination gave 2,4-diamino-2',3'-dideoxy derivative 19. Catalytic hydrogenation of 3 followed by debenzoylation afforded 2-aminopyrrolo[2,3-d]pyrimidine nucleoside 23. Among the compounds evaluated for their ability to inhibit the growth of HCMV (strain AD169) in MRC-5 cells using a plaque reduction assay, only 7 was significantly active in vitro with a 50% inhibitory concentration (IC50) of 3.7 micrograms/mL (TI > 125), whereas the IC50 value of ganciclovir (DHPG) was 3.2 micrograms/mL. Strain D16 of HCMV was more resistant to 7 (IC50 11 micrograms/mL) than the AD169 strain. When 7 was tested in combination with DHPG, the resultant anti-HCMV activity was found to be moderately synergistic with no evidence of antagonism. Nucleoside 7 also reduced episomal HBV replication in human hepatoblastoma 2.2.15 cells with an IC50 of 0.7 micrograms/mL (TI > 143). Development of cells harboring HBV which had become resistant to the drug was not observed with 7. Compound 7 also exhibited significant activity against herpes simplex virus types 1 and 2 (IC50 of 4.1 and 6.3 micrograms

  5. In Vitro α-Amylase Inhibition and Antioxidant Activities of Methanolic Extract of Amaranthus Caudatus Linn

    PubMed Central

    Kumar, Ashok; Khan, Saleemulla

    2011-01-01

    Objectives The present study was aimed to investigate the α-amylase inhibition and antioxidant activities of methanolic extract of Amaranthus caudatus Linn (MeAc). Methods Methanolic extract of Amaranthus caudatus was screened for α-amylase inhibition activity by CNPG3 method (2-chloro-p-nitrophenyl-α-D-maltotrioside) and antioxidant activity was evaluated by 1,1-diphenyl-2-picryl-hydrazile (DPPH) free radical scavenging, superoxide dismutase (SOD) scavenging, hydroxyl free radical scavenging, nitric oxide (NO) radical scavenging, and 2.2’-azinobis-3-ethylbenzothiazole-6-sulfonic acid (ABTS) radical scavenging assays. MeAc was also screened for non enzymatic hemoglycosylation. Results The methanolic extract of Amaranthus caudatus showed potent α-amylase inhibition activity (IC50 19.233 µg/ml). MeAc showed significant antioxidant activity in all the in vitro antioxidant models. Furthermore, the MeAc was found to be extremely effective in scavenging ABTS radical activity (IC50 48.75±1.1 µg/ml) when compared to DPPH (IC50 77.5±0.4 µg/ml), SOD (IC50 62.5±2.1 µg/ml), hydroxyl (IC50 88.50±1.8 µg/ml) and NO (IC50 67.5±2.2 µg/ml) scavenging activity. Conclusions The methanolic extract of A. caudatus showed potent α-amylase inhibition and antioxidant activities. PMID:22043408

  6. In Vitro Antiplasmodial Activity of Sesquiterpene Lactones from Ambrosia tenuifolia

    PubMed Central

    Sülsen, V.; Gutierrez Yappu, D.; Laurella, L.; Anesini, C.; Gimenez Turba, A.; Martino, V.; Muschietti, L.

    2011-01-01

    The in vitro antiplasmodial activity of Ambrosia tenuifolia organic extract and its isolated sesquiterpene lactones, psilostachyin and peruvin, has been evaluated against Plasmodium falciparum F32 and W2 strains. The cytotoxicity of both compounds was determined on lymphoid cells, and their corresponding selectivity indexes (SIs) were calculated. Peruvin was the most active compound on F32 strain of P. falciparum with a 50% inhibitory concentration value (IC50) of 0.3 μg/mL (1.1 μM) whereas psilostachyin showed activity on both strains (IC50 = 0.6 (2.1 μM) and 1.8 μg/mL (6.4 μM)). Fifty percent cytotoxic concentration (CC50) values (48 h) were 6.8 μg/mL (24.3 μM) and 10.0 μg/mL (37.9 μM) for psilostachyin and peruvin, respectively. PMID:21716685

  7. The inhibitory activity of aldose reductase in vitro by constituents of Garcinia mangostana Linn.

    PubMed

    Fatmawati, Sri; Ersam, Taslim; Shimizu, Kuniyoshi

    2015-01-15

    We investigated aldose reductase inhibition of Garcinia mangostana Linn. from Indonesia. Dichloromethane extract of the root bark of this tree was found to demonstrate an IC50 value of 11.98 µg/ml for human aldose reductase in vitro. From the dichloromethane fraction, prenylated xanthones were isolated as potent human aldose reductase inhibitors. We discovered 3-isomangostin to be most potent against aldose reductase, with an IC50 of 3.48 µM. PMID:25636870

  8. Compositional variations and anthelmentic activity of essential oils from rhizomes of different wild populations of Acorus calamus L. and its major component, beta-Asarone.

    PubMed

    Kumar, Ravendra; Prakash, Om; Pan, Anil K; Hore, Subrata K; Chanotiya, Chandan S; Mathela, Chandra S

    2009-02-01

    Hydro-distilled essential oils from Acorus calamus rhizomes collected from six different geographical zones in the northwest Himalayan region of Uttarakhand have been analyzed by GC and GC/MS. All the oils differed in their qualitative and quantitative make up, although beta-asarone was the major constituent of all of them. The essential oils and the isolated beta-asarone were screened for anthelmintic activity using contractility of Ascaridia galli. beta-Asarone, in particular, showed potent activity with IC50 values of 75.4 +/- 61.8 ng/mL. PMID:19370938

  9. ent-Abietane-type diterpenoids from the roots of Euphorbia ebracteolata with their inhibitory activities on LPS-induced NO production in RAW 264.7 macrophages.

    PubMed

    Liu, Zhi-guo; Li, Zhan-lin; Li, Da-Hong; Li, Ning; Bai, Jiao; Zhao, Feng; Meng, Da-li; Hua, Hui-ming

    2016-01-01

    Ten ent-abietane diterpenoids (1-10), including four new (1-4) and six known ones (5-10) were isolated from the roots of Euphorbia ebracteolata. Their structures were determined by 1D, 2D NMR, and HRESIMS. Compounds 2, 4, and 7 exhibited significant inhibitory activities on lipopolysaccharide (LPS)-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 0.69, 1.97, and 0.88μM, respectively. A primary structure-activity relationship was also discussed. PMID:26615888

  10. Four new phenolic acid with unusual bicycle [2.2.2] octane moiety from Clerodendranthus spicatus and their anti-inflammatory activity.

    PubMed

    Ma, Guo-Xu; Zhang, Xiao-Po; Li, Peng-Fei; Sun, Zhong-Hao; Zhu, Nai-Liang; Zhu, Yin-Di; Yang, Jun-Shan; Chen, De-Li; Wu, Hai-Feng; Xu, Xu-Dong

    2015-09-01

    Four new phenolic acids, clerodens A-D (1-4) possessing an unusual bicycle [2.2.2] octane moiety were isolated from the whole plants of Clerodendranthus spicatus. Their structures were elucidated by extensive spectroscopic methods, including NMR, MS, and ECD data. All isolates were evaluated for their anti-inflammatory activities on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7, and compound 4 showed significant inhibitory activities with IC50 value of 6.8 μM. PMID:26073946

  11. Active Inference, epistemic value, and vicarious trial and error.

    PubMed

    Pezzulo, Giovanni; Cartoni, Emilio; Rigoli, Francesco; Pio-Lopez, Léo; Friston, Karl

    2016-07-01

    Balancing habitual and deliberate forms of choice entails a comparison of their respective merits-the former being faster but inflexible, and the latter slower but more versatile. Here, we show that arbitration between these two forms of control can be derived from first principles within an Active Inference scheme. We illustrate our arguments with simulations that reproduce rodent spatial decisions in T-mazes. In this context, deliberation has been associated with vicarious trial and error (VTE) behavior (i.e., the fact that rodents sometimes stop at decision points as if deliberating between choice alternatives), whose neurophysiological correlates are "forward sweeps" of hippocampal place cells in the arms of the maze under consideration. Crucially, forward sweeps arise early in learning and disappear shortly after, marking a transition from deliberative to habitual choice. Our simulations show that this transition emerges as the optimal solution to the trade-off between policies that maximize reward or extrinsic value (habitual policies) and those that also consider the epistemic value of exploratory behavior (deliberative or epistemic policies)-the latter requiring VTE and the retrieval of episodic information via forward sweeps. We thus offer a novel perspective on the optimality principles that engender forward sweeps and VTE, and on their role on deliberate choice. PMID:27317193

  12. Active Inference, epistemic value, and vicarious trial and error

    PubMed Central

    Cartoni, Emilio; Rigoli, Francesco; Pio-Lopez, Léo; Friston, Karl

    2016-01-01

    Balancing habitual and deliberate forms of choice entails a comparison of their respective merits—the former being faster but inflexible, and the latter slower but more versatile. Here, we show that arbitration between these two forms of control can be derived from first principles within an Active Inference scheme. We illustrate our arguments with simulations that reproduce rodent spatial decisions in T-mazes. In this context, deliberation has been associated with vicarious trial and error (VTE) behavior (i.e., the fact that rodents sometimes stop at decision points as if deliberating between choice alternatives), whose neurophysiological correlates are “forward sweeps” of hippocampal place cells in the arms of the maze under consideration. Crucially, forward sweeps arise early in learning and disappear shortly after, marking a transition from deliberative to habitual choice. Our simulations show that this transition emerges as the optimal solution to the trade-off between policies that maximize reward or extrinsic value (habitual policies) and those that also consider the epistemic value of exploratory behavior (deliberative or epistemic policies)—the latter requiring VTE and the retrieval of episodic information via forward sweeps. We thus offer a novel perspective on the optimality principles that engender forward sweeps and VTE, and on their role on deliberate choice. PMID:27317193

  13. Inhibitory effects of polyphenols from grape pomace extract on collagenase and elastase activity.

    PubMed

    Wittenauer, Judith; Mäckle, Sonja; Sußmann, Daniela; Schweiggert-Weisz, Ute; Carle, Reinhold

    2015-03-01

    Breakdown and disorganization of extracellular matrix proteins like collagen, fibronectin and elastin are main characteristics of skin aging due to the enhanced activation of proteolytic enzymes such as collagenases and elastases. Inhibition of their enzymatic activities by natural plant compounds might be a promising approach to prevent extrinsic skin aging. Especially polyphenols are supposed to interact with those enzymes due to their molecular nature. In our investigation, extracts of pomace from Riesling grapes were analyzed for their inhibitory properties on collagenase as well as elastase. Crude grape pomace extract showed a dose-dependent inhibitory activity against both enzymes with IC50-values of 20.3μg/ml and 14.7μg/ml for collagenase and elastase activity, respectively. The extracts were fractionated into four fractions containing phenolic compounds differing in chemical structure and polarity. Except for the stilbene containing fraction, all other fractions showed inhibitory effects on both enzyme activities. The most pronounced impact was found for the hydrophilic low molecular weight polyphenols containing the free phenolic acids. In particular, gallic acid showed considerable inhibition values. EGCG was used as a positive control and showed a dose-dependent inhibition of collagenase activity (IC50=0.9mM). PMID:25598188

  14. Withanolides derived from Physalis peruviana (Poha) with potential anti-inflammatory activity.

    PubMed

    Sang-Ngern, Mayuramas; Youn, Ui Joung; Park, Eun-Jung; Kondratyuk, Tamara P; Simmons, Charles J; Wall, Marisa M; Ruf, Michael; Lorch, Sam E; Leong, Ethyn; Pezzuto, John M; Chang, Leng Chee

    2016-06-15

    Three new withanolides, physaperuvin G (1), with physaperuvins I (2), and J (3), along with seven known derivatives (4-10), were isolated from the aerial parts of Physalis peruviana. The structures of 1-3 were determined by NMR, X-ray diffraction, and mass spectrometry. Compounds 1-10 were evaluated in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells. Compounds 4, 5, and 10 with potent nitric oxide inhibitory activity in LPS-activated RAW 264.7 cells, with IC50 values in the range of 0.32-7.8μM. In addition, all compounds were evaluated for potential to inhibit tumor necrosis factor-alpha (TNF-α)-activated nuclear factor-kappa B (NF-κB) activity with transfected human embryonic kidney cells 293. Compounds 4-7 inhibited TNF-α-induced NF-κB activity with IC50 values in the range of 0.04-5.6μM. PMID:27210437

  15. The antioxidant and cytotoxic activities of Sonchus oleraceus L. extracts

    PubMed Central

    Yin, Jie; Kwon, Gu-Joong

    2007-01-01

    This study investigated in vitro antioxidant activity of Sonchus oleraceus L. by extraction solvent, which were examined by reducing power, hydroxyl radical-scavenging activity(HRSA) and 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assays. 70% MeOH extract had the greatest reducing power while EtOH extract had the greatest HRSA. The antioxidant activity of S. oleraceus extracts was concentration dependent and its IC50 values ranged from 47.1 to 210.5 µg/ml and IC50 of 70% MeOH, boiling water and 70% EtOH extracts were 47.1, 52.7 and 56.5 µg/ml, respectively. 70% MeOH extract of S. oleraceus contained the greatest amount of both phenolic and flavonoid contents. The extracts tested had greater nitrite scavenging effects at lower pH conditions. The cytotoxic activity showed that EtOH extract had the best activity against the growth of stomach cancer cell. These results suggest that S. oleraceus extract could be used as a potential source of natural antioxidants. PMID:20368937

  16. Anti-inflammatory and antioxidant activities of ethanolic extract of aerial parts of Vernonia patula (Dryand.) Merr.

    PubMed Central

    Hira, Arpona; Dey, Shubhra Kanti; Howlader, Md. Sariful Islam; Ahmed, Arif; Hossain, Hemayet; Jahan, Ismet Ara

    2013-01-01

    Objective To investigate the inflammatory and antioxidant activities of ethanolic extract of aerial part of Vernonia patula (Dryand.) Merr (EAV). Methods The anti-inflammatory activity of EAV was studied using carrageenan and histamine-induced rat paw edema test at different doses (100, 200 and 400 mg/kg body weight). DPPH free radical scavenging, nitric oxide scavenging, reducing power and Fe2+ ion chelating ability were used for determining antioxidant activities. Results The EAV, at the dose of 400 mg/kg, showed a significant anti-inflammatory activity (P<0.01) both in the carrageenan and histamine-induced oedema test models in rats, showing 62.86% and 64.42% reduction in the paw volume comparable to that produced by the standard drug indomethacin (67.26% and 66.01%) at 5 h respectively. In DPPH free radical scavenging test, IC50 value for EAV was found fairly significant 36.59 µg/mL when compared to the IC50 value of the reference standards ascorbic acid 8.97 µg/mL. The IC50 values of the extract and ascorbic acid were 47.72 and 12.39 µg/mL, respectively in nitric oxide scavenging assay. The IC50 value of the EAV (33.59 µg/mL) as percentage of Fe2+ ion chelating ability was also found significant compared to that of EDTA (9.16 µg/mL). The maximum absorbance for reducing power assay was found to be 1.928 at 100 µg/mL when compared to 2.449 for standard ascorbic acid. The total phenolic content was 198.81 mg/g of gallic acid equivalent. Acute toxicity test showed that the plant might be safe for pharmacological uses up to a dose level of 3 200 mg/kg of body weight in rats. Conclusions Therefore, the obtained results suggest the acute anti-inflammatory and antioxidant activities of the EAV and thus provide the scientific basis for the traditional uses of this plant part as a remedy for inflammations. PMID:24075345

  17. Phenolics from strawberry cv. Falandi and their antioxidant and α-glucosidase inhibitory activities.

    PubMed

    Yang, Dan; Xie, Haihui; Jiang, Yueming; Wei, Xiaoyi

    2016-03-01

    Three new phenolic glucosides, falandiosides A (1), B (2), and C (6) were isolated from strawberry (Fragaria×ananassa Duch.) cv. Falandi fruit, together with three flavone glucuronides (3-5), eleven lignan glycosides (12-22), and five others. Their structures were determined by spectroscopic methods. All the known phenolics were reported from strawberry for the first time. They were evaluated for antioxidant and α-glucosidase inhibitory activities. Three new and fifteen known phenolics showed potent 2,2'-azinobis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical cation scavenging activity with IC50 values of 22.50-4.28μM in comparison to l-ascorbic acid (14.21μM). Quercetin 3-(6-methylglucuronide) (4), (+)-isolariciresinol 9'-glucoside (12), and (-)-isolariciresinol 9'-glucoside (13) were active in scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. Moreover, compounds 12 and 13 had moderate ferric reducing antioxidant power (FRAP) values. Further, two new and seven known phenolics exhibited more potent α-glucosidase inhibitory activity with IC50 values of 537.43-25.39μM than acarbose (619.94μM). PMID:26471628

  18. Antioxidant Activity of Orange Flesh and Peel Extracted with Various Solvents

    PubMed Central

    Park, Jae-Hee; Lee, Minhee; Park, Eunju

    2014-01-01

    The aim of this study was to investigate the antioxidant activity of orange (Citrus auranthium) flesh (OF) and peel (OP) extracted with acetone, ethanol, and methanol. Antioxidant potential was examined by measuring total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (RSA), total radical-trapping anti-oxidant potential (TRAP), oxygen radical absorbance capacity (ORAC), and cellular antioxidant activity (CAA). The comet assay was used to determine the protective effects of OF and OP against H2O2-induced DNA damage. TPC was highest in the acetone extracts of OF and OP. DPPH RSA was also higher in the acetone extracts than in the ethanol extracts. The DPPH RSA was highest in the acetone extracts of OF. The TRAP and ORAC values of the all extracts increased in a dose-dependent manner. In the TRAP assay, the acetone extracts of OF and OP had the lowest IC50 values. In the CAA assay, the methanol and acetone extracts of OP had the lowest IC50 values. All of the samples protected against H2O2-induced DNA damage in human leukocytes, as measured by the comet assay, but the acetone extracts of OP had the strongest effect. These results suggest that acetone is the best solvent for the extraction of antioxidant compounds from OF and OP. Furthermore, the high antioxidant activity of OP, which is a by-product of orange processing, suggests that it can be used in nutraceutical and functional foods. PMID:25580393

  19. Phytochemical analysis and antioxidant activity of Hyssopus officinalis L. from Iran

    PubMed Central

    Fathiazad, Fatemeh; Mazandarani, Masoumeh; Hamedeyazdan, Sanaz

    2011-01-01

    Introduction: Hyssopus officinalis (L) (Hyssop, Family: Lamiaceae), one of the endemic Iranian perennial herb with a long history of medicinal use, was studied to detect some biologically active chemical constituents of the plant. Methods: The flavonoids of the hydromethanolic extract of the aerial parts of Hyssopus officinalis (L.) were studied by VLC and crystalisation of the major compound in subsequent fractions. Furthermore, the composition of its essential oil, total phenolic content and antioxidant activities were studied by GC-MS, Folin–Ciocalteau and DPPH reagents respectively. Results: Apigenin 7-O-β-D-glucuronide was isolated as the major flavonoid. All structural elucidation was performed by spectral means. A total of 20 compounds representing 99.97% of the oil have been identified. Myrtenylacetate, Camphor, Germacrene, Spathulenol were the main compounds The total phenol content of the n-butanol and ethylacetate extracts were determined spectrophotometrically according to the Folin–Ciocalteau procedure to be 246 mgGAE g-1 and 51 mgGAE g-1 in the aerial parts of Hyssopus officinalis . The antioxidant activities of apigenin 7-O-β-D-glucuronide, ethylacetate and n-butanol extracts were also determined by DPPH radical scavenging assay with IC50 values of 116×10-3, 103×10-3, 25×10-3 mg mL-1 respectively. The purified flavonoid showed weak radical scavenging activity (IC50 = 116×10-3mg mL-1). N-butanol extract, because of the highest content of total phenolic compounds (246 mgGAE100-1g) had the best antioxidant activity (IC50 = 25mg mL-1). Conclusion: On the whole, the findings of the study revealed that Hyssop possesses valuable antioxidant properties for culinary and possible medicinal use. PMID:24312758

  20. In vitro antiplasmodial activity, macronutrients and trace metals in the medicinal plants: Phyllanthus spp. and Alpinia conchigera Griff.

    PubMed

    Haslinda, M S; Aiyub, Z; Bakar, N K A; Tohar, N; Musa, Y; Abdullah, N R; Ibrahim, H; Awang, K

    2015-03-01

    An antiplasmodial screening of Phyllanthus debilis and Phyllanthus urinaria was carried out. The medicinal plants were extracted and evaluated for in vitro antiplasmodial activity against D10 (chloroquine-sensitive, CQS) and Gombak A (chloroquine-resistant, CQR) strains of Plasmodium falciparum. The methanolic crudes from the soxhlet extraction were active against both strains however, P. urinaria (IC50 8.9 μg/ml with CQR strain) exhibited better anti-malarial activity compared to P. debilis (IC50 12.2 μg/ml with CQR strain). Furthermore, the methanolic crude of P. urinaria obtained by the cold extraction has good anti-malarial activity towards CQS (IC50 4.1 μg/ml). The concentration of macronutrients (calcium and magnesium) and trace metals (copper, manganese, iron and zinc) from three Phyllanthus species i.e. P. debilis Klein ex Wild., Phyllanthus niruri L., P. urinaria L. and Alpinia conchigera Griff. were determined using microwave digestion method and analyzed by Flame Atomic Absorption Spectroscopy. Standard Reference Material 1547 (peach leaves) was used to validate the method throughout this study. The recovery values were in the range of 80% to 120% which were in very good agreement with the certified values. The three Phyllanthus species and leaves of A. conchigera showed the highest concentration of calcium compared to other metals and macronutrients studied. The significant presence of all the important macronutrients and trace metals which are essential for human health and well-being substantiate their use medicinally in traditional practices. PMID:25801263

  1. Synthesis, crystal structures, molecular docking, and in vitro biological activities of transition metals with 4-(2,3-dichlorophenyl)piperazine-1-carboxylic acid.

    PubMed

    Yang, Dan-Dan; Chen, Ya-Nan; Wu, Yu-Shan; Wang, Rui; Chen, Zhi-Jian; Qin, Jie; Qian, Shao-Song; Zhu, Hai-Liang

    2016-07-15

    Four novel mononuclear complexes, [Cd(L)2·2H2O] (1), [Ni(L)2·2H2O] (2) [Cu(L)2·H2O] (3), and [Zn(L)2·2H2O] (4) (CCDC numbers: 1444630-1444633 for complexes 1-4) (HL=4-(2,3-dichlorophenyl)piperazine-1-carboxylic acid) were synthesized, and have been characterized by IR spectroscopy, elemental analysis, and X-ray crystallography. Molecular docking study preliminarily revealed that complex 1 had potential telomerase inhibitory activity. In accordance with the result of calculation, in vitro tests of the inhibitory activities of complex 1 against telomerase showed complex 1 (IC50=8.17±0.91μM) had better inhibitory activities, while complexes 2, 3 and 4 showed no inhibitory activities. Antiproliferative activity in human cancer cell line HepG2 was further determined by MTT assays. The IC50 value (6.5±0.2μM) for the complex 1 having good inhibitory activity against HepG2 was at the same micromolar concentrations with cis-platinum (2.2±1.2μM). While the IC50 value for the metal-free ligand, complex 2, 3 and 4 was more than 100μM. These results indicated that telomerase was potentially an anticancer drug target and showed that complex 1 was a potent inhibitor of human telomerase as well as an antiproliferative compound. PMID:27241690

  2. Methicillin-resistant Staphylococcus aureus, Vancomycin-resistant Enterococcus faecalis and Enterococcus faecium active Dimeric Isobutyrylphloroglucinol from Ivesia gordonii

    PubMed Central

    Ahmed, Marwa H.; Ibrahim, Mohamed Ali; Zhang, Jin; Melek, Farouk R.; El-Hawary, Seham S.; Jacob, Melissa R.; Muhammad, Ilias

    2014-01-01

    Bioassay-guided fractionation of the chloroform soluble fraction of stem, leave, and flower extracts of the American plant Ivesia gordonii led to the isolation of a new dimeric acylphloroglucinol 3,3′-diisobutyryl-2,6′-dimethoxy-4,6,2′,4′-tetrahydroxy-5,5′dimethyldiphenyl methane (1), to which we have assigned the trivial name of ivesinol (1), together with a known monomeric acylphloroglucinol, 1,5-dihydroxy-2-(2′-methylpropionyl)-3-methoxy-6-methylbenzene (2). The structures of the isolated compounds were characterized using 1D- and 2D NMR spectroscopy, including COSY, HMQC, HMBC, and ROESY experiments as well as mass spectrometery. Ivesinol (1) showed potent activity against Staphylococcus aureus (SA) and methicillin-resistant S. aureus (MRSA) with IC50/MIC/MBC values of 0.10/1.25/>20 µg/mL and 0.05/0.31/>20 µg/mL, respectively (vs. IC50/MIC/MBC 0.133/0.5/1.0 µg/mL and 0.128/0.5/1.0 µg/mL of ciprofloxacin), while the corresponding monomer 2 was found to be less active. Compound 1 also demonstrated strong activity against vancomycin-resistant Enterococcus faecium (VRE) with IC50/MIC/MBC values 0.22/1.25/>20 µg/mL, whereas the reference standard ciprofloxacin was found to be inactive against this strain. In addition, compound 2 showed moderate activity against two species of Candida and Cryptococcus neoformans, while 1 was inactive against these fungi. In order to evaluate the influence of acyl group(s) in phloroglucinol (3) as a ligand, the mono- (4) and diacetylphloroglucinol (5) were prepared from 3, and evaluated for their in vitro SA, MRSA, and VRE activities, where 2,4-diacetylphloroglucinol (5) showed potent activity, like 1, against SA, MRSA, and VRE (ATCC 700221) with IC50/ MIC values of 0.27/2.5 µg/mL, 0.23/2.5 µg/mL, and 0.86/2.5 µg/mL, respectively, while 4 was inactive. PMID:24689296

  3. In vitro antitrypanosomal activity of the cyclodepsipeptides, cardinalisamides A-C, from the insect pathogenic fungus Cordyceps cardinalis NBRC 103832.

    PubMed

    Umeyama, Akemi; Takahashi, Koichi; Grudniewska, Aleksandra; Shimizu, Mina; Hayashi, Sayaka; Kato, Masayuki; Okamoto, Yasuko; Suenaga, Midori; Ban, Sayaka; Kumada, Toshio; Ishiyama, Aki; Iwatsuki, Masato; Otoguro, Kazuhiko; Omura, Satoshi; Hashimoto, Toshihiro

    2014-02-01

    During the search for new antitrypanosomal drug leads, three new antitrypanosomal compounds, cardinalisamides A-C (1-3), were isolated from cultures of the insect pathogenic fungus Cordyceps cardinalis NBRC 103832. Their structures were elucidated using MS analyses and extensive 2D-heteronuclear NMR. The absolute configurations of 1-3 were addressed by chemical degradation and Marfey's analysis. 1-3 showed in vitro antitrypanosomal activity against Trypanosoma brucei brucei with IC50 values of 8.56, 8.65 and 8.63 μg ml(-1), respectively. PMID:24084682

  4. Synthesis and cytotoxic activity of N-substituted thiosemicarbazones of 3-(3,4-methylenedioxy)phenylpropanal.

    PubMed

    Joselice e Silva, M; Alves, A J; Do Nascimento, S C

    1998-03-01

    Five new N-substituted thiosemicarbazones of 3-(3,4-methylenedioxy)phenylpropanal were synthesized. Safrole, a natural product obtained from sassafras oil (Ocotea pretiosa), was oxidized to alcohol using BH3-THF and H2O2, followed by oxidation to aldehyde using pyridinium dichromate (PDC) and condensation with five N-substituted derivatives of thiosemicarbazide. Tests were performed to evaluate the cytotoxic activity with continuous chain KB cells (epidermoide carcinoma of the floor of the mouth). Compounds 5 and 6 showed IC50 values of 1.5 and 4.6 micrograms/ml, respectively. PMID:9639871

  5. New sesquiterpenoids from the edible mushroom Pleurotus cystidiosus and their inhibitory activity against α-glucosidase and PTP1B.

    PubMed

    Tao, Qiao-Qiao; Ma, Ke; Bao, Li; Wang, Kai; Han, Jun-Jie; Zhang, Jin-Xia; Huang, Chen-Yang; Liu, Hong-Wei

    2016-06-01

    Nine new sesquiterpenoids, clitocybulol derivatives, clitocybulols G-O (1-9) and three known sesquiterpenoids, clitocybulols C-E (10-12), were isolated from the solid culture of the edible fungus Pleurotus cystidiosus. The structures of compounds 1-12 were determined by spectroscopic methods. The absolute configurations of compounds 1-9 were assigned via the circular dichroism (CD) data analysis. Compounds 1, 6 and 10 showed moderate inhibitory activity against protein tyrosine phosphatase-1B (PTP1B) with IC50 values of 49.5, 38.1 and 36.0μM, respectively. PMID:27085303

  6. New Hippolide Derivatives with Protein Tyrosine Phosphatase 1B Inhibitory Activity from the Marine Sponge Hippospongia lachne

    PubMed Central

    Piao, Shu-Juan; Jiao, Wei-Hua; Yang, Fan; Yi, Yang-Hua; Di, Ying-Tong; Han, Bing-Nan; Lin, Hou-Wen

    2014-01-01

    Five new sesterterpenoids, compounds 1–5, have been isolated from the sponge Hippospongia lachne off Yongxing Island in the South China Sea. The structures of compounds 1–5 were elucidated through extensive spectroscopic analysis, including HRMS, 1D, and 2D NMR experiments. The stereochemistry, including absolute configurations of these compounds, was determined by spectroscopic, chemical, and computational methods. Compounds 1 and 5 showed moderate protein tyrosine phosphatase 1B (PTP1B) inhibitory activities with IC50 values of 5.2 μM and 8.7 μM, respectively, more potent than previously reported hippolides. PMID:25007159

  7. Shikonin Inhibits Intestinal Calcium-Activated Chloride Channels and Prevents Rotaviral Diarrhea.

    PubMed

    Jiang, Yu; Yu, Bo; Yang, Hong; Ma, Tonghui

    2016-01-01

    Secretory diarrhea remains a global health burden and causes major mortality in children. There have been some focuses on antidiarrheal therapies that may reduce fluid losses and intestinal motility in diarrheal diseases. In the present study, we identified shikonin as an inhibitor of TMEM16A chloride channel activity using cell-based fluorescent-quenching assay. The IC50 value of shikonin was 6.5 μM. Short-circuit current measurements demonstrated that shikonin inhibited Eact-induced Cl(-) current in a dose-dependent manner, with IC50 value of 1.5 μM. Short-circuit current measurement showed that shikonin exhibited inhibitory effect against CCh-induced Cl(-) currents in mouse colonic epithelia but did not affect cytoplasmic Ca(2+) concentration as well as the other major enterocyte chloride channel conductance regulator. Characterization study found that shikonin inhibited basolateral K(+) channel activity without affecting Na(+)/K(+)-ATPase activities. In vivo studies revealed that shikonin significantly delayed intestinal motility in mice and reduced stool water content in a neonatal mice model of rotaviral diarrhea without affecting the viral infection process in vivo. Taken together, the results suggested that shikonin inhibited enterocyte calcium-activated chloride channels, the inhibitory effect was partially through inhbition of basolateral K(+) channel activity, and shikonin could be a lead compound in the treatment of rotaviral secretory diarrhea. PMID:27601995

  8. ACE-inhibitory activity of enzymatic protein hydrolysates from lupin and other legumes.

    PubMed

    Boschin, Giovanna; Scigliuolo, Graziana Maria; Resta, Donatella; Arnoldi, Anna

    2014-02-15

    The objective of this investigation was to compare the angiotensin converting enzyme (ACE)-inhibitory activity of the hydrolysates obtained by pepsin digestion of proteins of some legumes, such as chickpea, common bean, lentil, lupin, pea, and soybean, by using the same experimental procedure. The ACE-inhibitory activity was measured by using the tripeptide hippuryl-histidyl-leucine (HHL), as model peptide, and HPLC-DAD, as analytical method. The peptide mixtures of all legumes were active, with soybean and lupin the most efficient, with IC50 values of 224 and 226 μg/ml, respectively. Considering the promising results obtained with lupin, and aiming to identify the protein(s) that release(s) the peptides responsible for the activity, the peptides obtained from the pepsin digestion of some industrial lupin protein isolates and purified protein fractions were tested. The most active mixture, showing an IC50 value of 138 μg/ml, was obtained hydrolysing a mixture of lupin α+β conglutin. PMID:24128446

  9. In vitro antioxidant and antiproliferative activities of flavonoids from Ailanthus excelsa (Roxb.) (Simaroubaceae) leaves.

    PubMed

    Said, Ataa; Tundis, Rosa; Hawas, Usama W; El-Kousy, Salah M; Rashed, Khaled; Menichini, Federica; Bonesi, Marco; Huefner, Antje; Loizzo, Monica Rosa; Menichinib, Francesco

    2010-01-01

    The present study aimed to investigate the chemical composition, and the antioxidant and antiproliferative activities of Ailanthus excelsa, a plant used in Egyptian traditional medicine. Chromatographic separation of a methanol extract of A. excelsa leaves yielded four flavones, namely apigenin (1), apigenin 7-O-beta-glucoside (2), luteolin (3), and luteolin 7-O-beta-glucoside (4), and seven flavonols, namely kaempferol (5), kaempferol 3-O-alpha-arabinoside (6), kaempferol 3-O-beta-galactoside (7), quercetin (8), quercetin 3-O-alpha-arabinoside (9), quercetin 3-O-beta-galactoside (10), and quercetin 3-O-rutinoside (11). The A. excelsa extract tested in different in vitro systems (DPPH and FRAP assays) showed significant antioxidant activity. The potential antiproliferative activity of the A. excelsa extract and isolated flavonoids against five human cancer cell lines such as ACHN, COR-L23, A375, C32, and A549 was investigated in vitro by the SRB assay in comparison with one normal cell line, 142BR. The extract exhibited the highest inhibitory activity against C32 cells with an IC50 value of 36.5 microg ml(-1). Interesting activity against COR-L23 was found with 10 (IC50 value of 3.2 microg ml(-1)). Compounds 1 and 3 inhibited cell growth in both amelanotic melanoma and malignant melanoma cells. PMID:20469635

  10. Chemical composition and biological activity of the essential oil from Thymus lanceolatus.

    PubMed

    Khadir, Abdelmounaim; Sobeh, Mansour; Gad, Haidy A; Benbelaid, Fethi; Bendahou, Mourad; Peixoto, Herbenya; Sporer, Frank; Ashour, Mohamed L; Wink, Michael

    2016-01-01

    Thymus lanceolatus is a rare species, which grows wild in Algeria and Tunis. It is used traditionally as a drink and to flavor and preserve meat and poultry. The composition of the essential oil was determined by GLC/FID and GLC/MS. Forty-nine components were identified and quantified, accounting for 96.75% of the total detected components in the oil. The oxygenated monoterpenes (74.85%) constitute the major class of volatile secondary metabolites in the oil. Thymol was the most abundant constituent (69.61%) followed by γ-terpinene (8.38%). The antioxidant activity was evaluated using both diphenylpicrylhydrazyl (DPPH˙) reduction and 2-deoxyribose (2-DR) degradation prevention methods. The oil showed a very potent antioxidant activity with IC(50) values of 0.20 ± 0.07 and 4.96 ± 0.39 μg/mL for the DPPH˙ and 2-DR methods, respectively. The antimicrobial activity of the oil was assessed using the agar diffusion method, and the in vitro cytotoxicity on five different cancer cells was examined using the MTT assay. The oil revealed promising inhibitory activity against Gram positive bacteria, especially Bacillus subtilis and Streptococcus pyogenes with an MIC value of 62.5 μg/mL. Additionally, the highest cytotoxic activity was observed against the HL-60 cells with an IC(50) of 113.5 μg/mL. These results validate some of their traditional uses in food preservation. PMID:27155003

  11. Cytotoxic and apoptosis-inducing activities of steviol and isosteviol derivatives against human cancer cell lines.

    PubMed

    Ukiya, Motohiko; Sawada, Shingo; Kikuchi, Takashi; Kushi, Yasunori; Fukatsu, Makoto; Akihisa, Toshihiro

    2013-02-01

    Seventeen steviol derivatives, i.e., 2-18, and 19 isosteviol derivatives, i.e., 19-37, were prepared from a diterpenoid glycoside, stevioside (1). Upon evaluation of the cytotoxic activities of these compounds against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK-BR-3) cancer cell lines, nine steviol derivatives, i.e., 5-9 and 11-14, and five isosteviol derivatives, i.e., 28-32, exhibited activities with single-digit micromolar IC(50) values against one or more cell lines. All of these active compounds possess C(19)-O-acyl group, and among which, ent-kaur-16-ene-13,19-diol 19-O-4',4',4'-trifluorocrotonate (14) exhibited potent cytotoxicities against four cell lines with IC(50) values in the range of 1.2-4.1 μM. Compound 14 induced typical apoptotic cell death in HL60 cells upon evaluation of the apoptosis-inducing activity by flow-cytometric analysis. These results suggested that acylation of the 19-OH group of kaurane- and beyerane-type diterpenoids might be useful for enhancement of their cytotoxicities with apoptosis-inducing activity. PMID:23418165

  12. In vitro antiplasmodial activity of benzophenones and xanthones from edible fruits of Garcinia species.

    PubMed

    Lyles, James T; Negrin, Adam; Khan, Shabana I; He, Kan; Kennelly, Edward J

    2014-06-01

    Species of Garcinia have been used to combat malaria in traditional African and Asian medicines, including Ayurveda. In the current study, we have identified antiplasmodial benzophenone and xanthone compounds from edible Garcinia species by testing for in vitro inhibitory activity against Plasmodium falciparum. Whole fruits of Garcinia xanthochymus, G. mangostana, G. spicata, and G. livingstonei were extracted and tested for antiplasmodial activity. Garcinia xanthochymus was subjected to bioactivity-guided fractionation to identify active partitions. Purified benzophenones (1-9) and xanthones (10-18) were then screened in the plasmodial lactate dehydrogenase assay and tested for cytotoxicity against mammalian (Vero) cells. The benzophenones guttiferone E (4), isoxanthochymol (5), and guttiferone H (6), isolated from G. xanthochymus, and the xanthones α-mangostin (15), β-mangostin (16), and 3-isomangostin (17), known from G. mangostana, showed antiplasmodial activity with IC50 values in the range of 4.71-11.40 µM. Artemisinin and chloroquine were used as positive controls and exhibited IC50 values in the range of 0.01-0.24 µM. The identification of antiplasmodial benzophenone and xanthone compounds from G. xanthochymus and G. mangostana provides evidence for the antiplasmodial activity of Garcinia species and warrants further investigation of these fruits as dietary sources of chemopreventive compounds. PMID:24963617

  13. Shikonin Inhibits Intestinal Calcium-Activated Chloride Channels and Prevents Rotaviral Diarrhea

    PubMed Central

    Jiang, Yu; Yu, Bo; Yang, Hong; Ma, Tonghui

    2016-01-01

    Secretory diarrhea remains a global health burden and causes major mortality in children. There have been some focuses on antidiarrheal therapies that may reduce fluid losses and intestinal motility in diarrheal diseases. In the present study, we identified shikonin as an inhibitor of TMEM16A chloride channel activity using cell-based fluorescent-quenching assay. The IC50 value of shikonin was 6.5 μM. Short-circuit current measurements demonstrated that shikonin inhibited Eact-induced Cl- current in a dose-dependent manner, with IC50 value of 1.5 μM. Short-circuit current measurement showed that shikonin exhibited inhibitory effect against CCh-induced Cl- currents in mouse colonic epithelia but did not affect cytoplasmic Ca2+ concentration as well as the other major enterocyte chloride channel conductance regulator. Characterization study found that shikonin inhibited basolateral K+ channel activity without affecting Na+/K+-ATPase activities. In vivo studies revealed that shikonin significantly delayed intestinal motility in mice and reduced stool water content in a neonatal mice model of rotaviral diarrhea without affecting the viral infection process in vivo. Taken together, the results suggested that shikonin inhibited enterocyte calcium-activated chloride channels, the inhibitory effect was partially through inhbition of basolateral K+ channel activity, and shikonin could be a lead compound in the treatment of rotaviral secretory diarrhea. PMID:27601995

  14. Resveratrol-Related Polymethoxystilbene Glycosides: Synthesis, Antiproliferative Activity, and Glycosidase Inhibition.

    PubMed

    Cardullo, Nunzio; Spatafora, Carmela; Musso, Nicolò; Barresi, Vincenza; Condorelli, Daniele; Tringali, Corrado

    2015-11-25

    A small library of polymethoxystilbene glycosides (20-25) related to the natural polyphenol resveratrol have been synthesized and subjected, together with their aglycones 17-19, to an antiproliferative activity bioassay toward Caco-2 and SH-SY5Y cancer cells. Six of the compounds exhibit antiproliferative activity against at least one cell line. In particular, compounds 17 and 18 proved highly active on at least one of the two cell cultures. Compound 18 showed a GI50 value of 3 μM against Caco-2 cells, a value comparable to that of the anticancer drug 5-fluorouracil. The closely related compound 19 proved inactive, and its conjugates 22 and 25 showed weak cell growth inhibition. The results indicate that minimal differences in the structure of both polymethoxystilbenes and their glycosides can substantially affect the antiproliferative activity. The possible hydrolytic release of the aglycones 17-19 by β-glucosidase or β-galactosidase was also evaluated. Compounds 20-25 were also tested as potential β-glucosidase, β-galactosidase, and α-glucosidase inhibitors. A promising inhibitory activity toward α-glucosidase was observed for 21 (IC50 = 78 μM) and 25 (IC50 = 70 μM), which might be indicative of their potential as lead compounds for development of antidiabetic or antiobesity agents. PMID:26539626

  15. Chemical composition and biological activities of essential oils of Eremanthus erythropappus (DC) McLeisch (Asteraceae).

    PubMed

    Silvério, Marcelo S; Del-Vechio-Vieira, Glauciemar; Pinto, Míriam A O; Alves, Maria S; Sousa, Orlando V

    2013-01-01

    The chemical composition of the essential oils obtained by hydrodistillation of different parts of Eremanthus erythropappus, including leaves, branches and inflorescences, was investigated by Gas Chromatography and Gas Chromatography/Mass Spectrometry. The antimicrobial activity of the oils was assessed by the disc diffusion and microdilution methods, while the antioxidant activity was evaluated by DPPH and reducing power tests. The main compounds found in the essential oils derived from the inflorescences and leaves were β-caryophyllene, germacrene-D, α-copaene and β-pinene. α-Bisabolol was the major component in the branches. The oils were active against Staphylococcus aureus, Streptococcus pyogenes and fungi, but not Escherichia coli and Pseudomonas aeruginosa. The MIC values ranged from 0.01 to 0.50 mg/mL. Using the DPPH test, the IC50 values ranged from 38.77 ± 0.76 to 102.24 ± 1.96 μg/mL, while the reducing power test produced IC50 values between 109.85 ± 1.68 and 169.53 ± 0.64 μg/mL. The results revealed that the E. erythropappus oils are new promising potential sources of antimicrobial and antioxidant compounds with good future practical applications for human health. PMID:23959191

  16. Screening of Different Extracts from Artemisia Species for Their Potential Antimalarial Activity

    PubMed Central

    Mojarrab, Mahdi; Naderi, Rozhin; Heshmati Afshar, Fariba

    2015-01-01

    The formation of hemozoin (malaria pigment) has been proposed as an ideal drug target for antimalarial screening programs. In this study, we used an improved, cost-effective and high-throughput spectrophotometric assay to screen plant extracts for finding novel antimalarial plant sources. Fifteen extracts with different polarity from three Iranian Artemisia species, A. ciniformis, A. biennis and A. turanica, were assessed for their antimalarial activity by in-vitro β-hematin formation assay. The most potent effect was observed in dichloromethane (DCM) extract of A. ciniformis with IC50 and IC90 values of 0.92 ± 0.01 and 1.29 ± 0.02 mg/mL, respectively. Ethyl acetate (EtOAC) extracts of A. biennis and A. turanica also showed significant antimalarial activities with IC50 values of 1.11 ± 0.02 and 1.35 ± 0.08 mg/mL and IC90 values of 1.22 ± 0.04 and 2.81 ± 0.21 mg/mL, respectively. Based on these results, it is possible to conclude that the components with strong antimalarial activity have been concentrated in the medium-polar extracts. PMID:25901169

  17. Effects of exposure to oxamyl, carbofuran, dichlorvos, and lindane on acetylcholinesterase activity in the gills of the Pacific oyster Crassostrea gigas.

    PubMed

    Anguiano, Gerardo A; Amador, Alejandro; Moreno-Legorreta, Manuel; Arcos-Ortega, Fabiola; Vazquez-Boucard, Celia

    2010-08-01

    Acetylcholinesterase (AChE) activity has been used to test the exposure of mollusk bivalves to pesticides and other pollutants. The Pacific oyster Crassostrea gigas is a species with a worldwide distribution, and it has a high commercial value. The use of this species as a bioindicator in the marine environment, and the use of measurements of AChE activity in tissues of C. gigas require prior evaluation of organisms exposed to several toxic compounds in the laboratory. In our study, the effects of pesticides on AChE activity in the gills and mantle tissues of C. gigas were analyzed by exposing animals to organophosphate (dichlorvos), carbamate (carbofuran and oxamyl), and organochlorine (lindane) pesticides. Adult Pacific oysters were exposed to several concentrations (0.1-200 microM) of dichlorvos, carbofuran, and oxamyl for 96 h, and lindane (1.0 and 2.5 microM) was applied for 12 days. In gill tissues, all pesticides analyzed caused a decrease in AChE activity when compared to the control unexposed group. The mean inhibition concentration (IC(50)) values were determined for dichlorvos, carbofuran, and oxamyl pesticides. Dichlorvos had the highest toxic effect, with an IC(50) of 1.08 microM; lesser effects were caused by oxamyl and carbofuran, with IC(50)s of 1.67 and 3.03 microM, respectively. This study reports the effects of pesticides with several chemical structures and validates measurement of AChE activity in the gill tissues of C. gigas for use in environmental evaluations or food quality tests. PMID:19449386

  18. Dual effects of alpha-arbutin on monophenolase and diphenolase activities of mushroom tyrosinase.

    PubMed

    Qin, Liang; Wu, Yang; Liu, Youting; Chen, Yiming; Zhang, Peng

    2014-01-01

    The effects of α-arbutin on the monophenolase and diphenolase activities of mushroom tyrosinase were investigated. The results showed that α-arbutin inhibited monophenolase activity but it activated diphenolase activity. For monophenolase activity, IC50 value was 4.5 mmol · L(-1) and 4.18 mmol · L(-1) of α-arbutin could extend the lag time from 40.5 s to 167.3 s. Alpha- arbutin is proposed to be regarded as a triphenolic substrate by the enzyme during catalyzation, leading to the suicide inactivation of the active site of tyrosinase. For diphenolase activity, α-arbutin acted as an activator and its activation mechanism was mixed type activation. To reveal such activation, it should be mainly refered to the conformational changes in tyrosinase caused by the interaction of α-arbutin with residues located at the entrance to the active site, and the decrease of the effect of suicide inactivation. PMID:25303458

  19. Antitumor Activity of Gold(I), Silver(I) and Copper(I) Complexes Containing Chiral Tertiary Phosphines

    PubMed Central

    McKeage, Mark J.; Papathanasiou, Peter; Sjaarda, Allan; Swiegers, Gerhard F.; Waring, Paul; Wild, S. Bruce

    1998-01-01

    The in vitro cytotoxicities of a number of gold(I), silver(I) and copper(I) complexes containing chiral tertiary phosphine ligands have been examined against the mouse tumour cell lines P815 mastocytoma, B16 melanoma [gold(I) and silver(I) compounds] and P388 leukaemia [gold(I) complexes only] with many of the complexes having IC50 values comparable to that of the reference compounds cis-diamminedichloroplatinum(ll), cisplatin, and bis[1,2-bis(diphenylphosphino) ethane]gold(I) iodide. The chiral tertiary phosphine ligands used in this study include (R)-(2-aminophenyl)methylphenylphosphine; (R,R)-, (S,S)- and (R*,R*)-1,2-phenylenebis(methylphenylphosphine); and (R,R)-, (S,S)- and (R*,R*)-bis{(2-diphenylphosphinoethyl)phenylphosphino}ethane. The in vitro cytotoxicities of gold(I) and silver(I) complexes containing the optically active forms of the tetra(tertiary phosphine) have also been examined against the human ovarian carcinoma cell lines 41M and CH1, and the cisplatin resistant 41McisR, CH1cisR and SKOV-3 tumour models. IC50 values in the range 0.01 - 0.04 μM were determined for the most active compounds, silver(I) complexes of the tetra(tertiary phosphine). Furthermore, the chirality of the ligand appeared to have little effect on the overall activity of the complexes: similar IC50 data were obtained for complexes of a particular metal ion with each of the stereoisomeric forms of a specific ligand. PMID:18475846

  20. Novel 5-Substituted 2-(Aylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl)benzenesulfonamides: Synthesis, Molecular Structure, Anticancer Activity, Apoptosis-Inducing Activity and Metabolic Stability.

    PubMed

    Żołnowska, Beata; Sławiński, Jarosław; Pogorzelska, Aneta; Szafrański, Krzysztof; Kawiak, Anna; Stasiłojć, Grzegorz; Belka, Mariusz; Ulenberg, Szymon; Bączek, Tomasz; Chojnacki, Jarosław

    2016-01-01

    A series of novel 5-substituted 2-(arylmethylthio)-4-chloro-N-(5-aryl-1,2,4-triazin-3-yl) benzenesulfonamide derivatives 27-60 have been synthesized by the reaction of aminoguanidines with an appropriate phenylglyoxal hydrate in glacial acetic acid. A majority of the compounds showed cytotoxic activity toward the human cancer cell lines HCT-116, HeLa and MCF-7, with IC50 values below 100 μM. It was found that for the analogues 36-38 the naphthyl moiety contributed significantly to the anticancer activity. Cytometric analysis of translocation of phosphatidylserine as well as mitochondrial membrane potential and cell cycle revealed that the most active compounds 37 (HCT-116 and HeLa) and 46 (MCF-7) inhibited the proliferation of cells by increasing the number of apoptotic cells. Apoptotic-like, dose dependent changes in morphology of cell lines were also noticed after treatment with 37 and 46. Moreover, triazines 37 and 46 induced caspase activity in the HCT-116, HeLa and MCF-7 cell lines. Selected compounds were tested for metabolic stability in the presence of pooled human liver microsomes and NADPH, both R² and Ar = 4-CF₃-C₆H₄ moiety in 2-(R²-methylthio)-N-(5-aryl-1,2,4-triazin-3-yl)benzenesulfonamides simultaneously increased metabolic stability. The results pointed to 37 as a hit compound with a good cytotoxicity against HCT-116 (IC50 = 36 μM), HeLa (IC50 = 34 μM) cell lines, apoptosis-inducing activity and moderate metabolic stability. PMID:27338337

  1. Triterpenoids from the leaves of Alphitonia xerocarpus Baill and their biological activity.

    PubMed

    Muhammad, Dima; Lalun, Nathalie; Bobichon, Hélène; Le Magrex Debar, Elisabeth; Gangloff, Sophie C; Nour, Mohammed; Voutquenne-Nazabadioko, Laurence

    2016-09-01

    Ten previously undescribed triterpenoid saponins and a previously undescribed norlupane triterpenoid were isolated, with three known saponins, four known flavonoids, two known lupane derivatives, sitosterol and 6'-heptadecanoyl-3-O-β-d-glucopyranosylsitosterol from the leaves of Alphitonia xerocarpus (Rhamnaceae), an endemic tree of New Caledonia. The chemical structures of the purified compounds were identified by nuclear magnetic resonance and mass spectrometry. The isolated compounds were tested for their antioxidant, antityrosinase, antibacterial and cytotoxic activity. The aqueous methanol extract showed antioxidant activity (DPPH assay) due to the presence of rutin. Ceanothenic acid showed good cytotoxic activity against a KB cell line (IC50 = 2.6 μM) and antibacterial activity against Staphylococcus aureus and Enterococcus faecalis with MIC values of 8 and 16 μg/mL, respectively. The previously undescribed 29-hydroxyceanothenic acid exhibited moderate cytotoxic activity (IC50 = 10 μM), good antibacterial activity against S. aureus (MIC = 4 μg/mL) and moderate antibacterial activity against E. faecalis (MIC = 16 μg/mL). PMID:27452452

  2. Interactions of ( sup 3 H)amphetamine with rat brain synaptosomes. II. Active transport

    SciTech Connect

    Zaczek, R.; Culp, S.; De Souza, E.B. )

    1991-05-01

    The accumulation of 5 nM d-({sup 3}H)amphetamine (d-({sup 3}H)AMPH) into rat brain synaptosomes was examined using physiological buffer conditions. The accumulation of d-({sup 3}H)AMPH into striatal synaptosomes was saturable, of high affinity, ouabain-sensitive and temperature-dependent, suggesting an active transport phenomenon. Eadee-Hofstee analysis of striatal d-({sup 3}H)AMPH transport (AMT) saturation isotherms indicated an apparent Km of 97 nM and a Vmax of 3.0 fmol/mg tissue/min. Lesion of the striatal dopaminergic innervation led to equivalent decreases of ({sup 3}H) dopamine (DA) transport and AMT, indicating that AMT occurs in DA terminals. Furthermore, AMT was not evident in cerebral cortex, a brain region with a paucity of DA terminals. In competition studies, AMT was stereospecific; d-AMPH (IC50 = 60 nM) was an 8-fold more potent inhibitor of the transport than its I-isomer (IC50 = 466 nM). DA(IC50 = 257 nM), DA uptake blockers and substrates were found to be potent inhibitors of AMT: GBR12909 IC50 = 5 nM; methamphetamine IC50 = 48 nM; methylphenidate IC50 = 53 nM; and cocaine IC50 = 172 nM. In contrast, serotonin was relatively weak in inhibiting AMT (IC50 = 7.9 microM). There was a highly significant (P less than .001; slope = 1.2) linear correlation between the AMT-inhibiting potencies of AMPH analogs and their potencies in stimulating locomotor activity in rodents. AMT may be important in the low dose effects of AMPH such as increased locomotor activity in rodents and stimulant activity in man. Differences between AMT and d-({sup 3}H)AMPH sequestration described earlier, as well as their possible relevance to behavioral and neurochemical sequelae of AMPH administration are also discussed.

  3. In vitro activity of Triclisia patens and some bisbenzylisoquinoline alkaloids against Leishmania donovani and Trypanosoma brucei brucei.

    PubMed

    del Rayo Camacho, Maria; Phillipson, J David; Croft, Simon L; Rock, Peter; Marshall, Sarah J; Schiff, Paul L

    2002-08-01

    In the search for antiprotozoal compounds from natural sources, Triclisia patens displayed activity against L. donovani promastigotes (IC(50) = 1.5 microg/mL) and T. b. brucei blood stream trypomastigote forms (IC(50) = 31.25 microg/mL). In addition, a total of 20 bisbenzylisoquinoline alkaloids were screened for antileishmanial and antitrypanosomal activity in vitro. Fangchinoline (IC(50) = 0.39 microM) was found to be as active as the standard pentamidine against Leishmania donovani promastigotes. Phaeanthine was three-fold more active (IC(50) = 2.41 microM; 1.5 microg/mL) than the standard drug Pentostam against L. donovani amastigotes, but at this concentration was toxic to murine macrophages. In contrast, cocsoline (IC(50) = 12.3 microM; 6.76 microg/mL) was as active as Pentostam, and was not toxic to macrophages at this concentration. Thalisopidine showed the strongest activity (IC(50) = 1.14 microM) against Trypanosoma brucei brucei blood stream form trypomastigotes, but was less active than pentamidine. PMID:12203262

  4. Entrapment into nanoemulsions potentiates the anticancer activity of tocotrienols against the highly malignant (+SA) mouse mammary epithelial cells.

    PubMed

    Alayoubi, Alaadin; Ayoub, Nehad M; Malaviya, Abhita; Sylvester, Paul W; Nazzal, Sami

    2014-05-01

    The highly malignant +SA mouse mammary epithelial cells were used as the model cell line over the years to establish the anticancer activity of tocotrienols. Tocotrienols, however, have poor oral bioavailability and were therefore entrapped into parenteral nanoemulsions for parenteral administration. The objective of this work was to test whether the activity of tocotrienols in lipid nanoemulsions against the +SA cells was retained. A secondary objective was to test whether stabilizing the nanoemulsions with poloxamer or sodium oleate would affect their activity. Nanoemulsions were found to be significantly more potent than tocotrienol/albumin conjugate. The IC50 values of the poloxamer and sodium oleate nanoemulsions were 3 and 6 microM, respectively, whereas the IC50 value of the conjugate was 10 microM. The antiproliferative activity of the nanoemulsions was also found to inversely correlate with particle size. No activity was observed with nanoemulsions loaded with alpha-tocopherol or vehicle, which confirmed the cytotoxic activity of tocotrienols and the potential use of nanoemulsions in cancer therapy. PMID:24734680

  5. Preparation of the Branch Bark Ethanol Extract in Mulberry Morus alba, Its Antioxidation, and Antihyperglycemic Activity In Vivo

    PubMed Central

    Wang, Shu; Fang, Meng; Ma, Yong-Lei

    2014-01-01

    The biological activities of the branch bark ethanol extract (BBEE) in the mulberry Morus alba L. were investigated. The determination of active component showed that the flavonoids, phenols, and saccharides are the major components of the ethanol extract. The BBEE had a good scavenging activity of the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical with around 100 μg/mL of IC50 value. In vitro assay revealed that the BBEE strongly inhibited both α-glucosidase and sucrase activities whose IC50 values were 8.0 and 0.24 μg/mL, respectively. The kinetic analysis showed that the BBEE as a kind of α-glucosidase inhibitor characterized a competitive inhibition activity. Furthermore, the carbohydrate tolerance of the normal mice was obviously enhanced at 0.5 h (P < 0.05) and 1.0 h (P < 0.05) after the BBEE intragastric administration as compared to negative control. At 0.5, 1.0, 1.5, and 2.0 h after the intragastric administration with starch, the postprandial hyperglycemia of the type 2 diabetic mice can be significantly decreased (P < 0.01) by supplying various concentrations of the BBEE (10–40 mg/kg body weight). Therefore, the BBEE could effectively inhibit the postprandial hyperglycemia as a novel α-glucosidase activity inhibitor for the diabetic therapy. PMID:24587809

  6. Cytotoxic activity of Macrosolen parasiticus (L.) Danser on the growth of breast cancer cell line (MCF-7)

    PubMed Central

    Sodde, Vijay Kumar; Lobo, Richard; Kumar, Nimmy; Maheshwari, Rajalekshmi; Shreedhara, C. S.

    2015-01-01

    Background: Macrosolen parasiticus (L.) Danser belonging to Loranthaceaea (mistletoe family) is a parasitic plant that grows on different host plants such as mango, jack fruit, peepal, neem tree, etc., This study was aimed to investigate the anti-cancer activity of methanolic and aqueous extract of stem of M. parasiticus. Objectives: To investigate the in vitro cytotoxic potential of the methanolic and aqueous extracts from stems of M. parasiticus against MCF-7 breast cancer cells by brine shrimp lethality (BSL) bioassay, MTT assay and sulforhodamine B (SRB) assay. Materials and Methods: The extracts were tested in human breast cancer cell lines in vitro for percentage cytotoxicity, apoptosis by acridine orange/ethidium bromide staining, LD50 and IC50 values after treatment with M. parasiticus extracts. Results: In BSL bioassay, aqueous extract showed more significant (P < 0.01) cytotoxicity with LD50 82.79 ± 2.67 μg/mL as compared to methanolic extract with LD50 125 ± 3.04 μg/mL. The methanolic extract of M. parasiticus showed IC50 97.33 ± 3.75 μg/mL (MTT) (P < 0.05) and 94.58 ± 3.84 μg/mL (SRB) (P < 0.01) assays against MCF-7. The aqueous extract of M. parasiticus demonstrated higher activity with IC50 59.33 ± 3.3 μg/mL (MTT) (P < 0.01) and 51.9 ± 1.87 μg/mL (SRB)(P < 0.01) assays, after 48 h of exposure and thus showed significant dose-dependent cytotoxic activity. Conclusion: The finding demonstrated that both extracts of M. parasiticus showed significant cytotoxic activity, however aqueous extract demonstrated higher activity against MCF-7 breast cancer cells. PMID:26109761

  7. Chemical composition and in vitro antitrypanosomal activity of fractions of essential oil from Cymbopogon nardus L.

    PubMed

    Muhd Haffiz, J; Norhayati, I; Getha, K; Nor Azah, M A; Mohd Ilham, A; Lili Sahira, H; Roshan Jahn, M S; Muhd Syamil, A

    2013-03-01

    Essential oil from Cymbopogon nardus was evaluated for activity against Trypanosoma brucei brucei BS221 (IC50 = 0.31 ± 0.03 μg/mL) and cytotoxic effect on normal kidney (Vero) cells (IC50 = >100 μg/mL). The crude essential oil was subjected to various chromatography techniques afforded active sub fractions with antitrypanosomal activity; F4 (IC50 = 0.61 ± 0.06 μg/mL), F6 (IC50= 0.73 ± 0.33 μg/mL), F7 (IC50 = 1.15 ± 0 μg/mL) and F8 (IC50 = 1.11 ± 0.01 μg/mL). These active fractions did not exhibit any toxic effects against Vero cell lines and the chemical profiles investigation indicated presence of α-and γ-eudesmol, elemol, α-cadinol and eugenol by GC/MS analysis. PMID:23665703

  8. Antioxidant activity-guided separation of coumarins and lignan from Melicope glabra (Rutaceae).

    PubMed

    Kassim, Nur Kartinee; Rahmani, Mawardi; Ismail, Amin; Sukari, Mohd Aspollah; Ee, Gwendoline Cheng Lian; Nasir, Nadiah Md; Awang, Khalijah

    2013-08-15

    The ethyl acetate and methanol bark extracts of Melicope glabra were evaluated for their antioxidant capacities by 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity and β-carotene bleaching/linoleic acid system. Both extracts exhibited strong inhibition against the DPPH radical (IC50 values of 24.81 and 13.01 μg ml(-1), respectively) and strong antioxidant activity in β-carotene bleaching assay. Both samples were found to have high phenolic content with values of 39 and 44 mg GAE/g as indicated by Follin-Ciocalteau's reagent. Antioxidant TLC assay-guided isolation on the methanol extract led to the isolation of a new pyranocoumarin, glabranin (1), umbelliferone (2), scopoletin (3) and sesamin (4), and their structures were determined by spectroscopy. Compounds (1-3) showed significant activities on DPPH free radical with the IC50 of 240.20, 810.02 and 413.19 μg ml(-1), respectively. However, in β-carotene bleaching assay, sesamin (4) showed higher inhibitory activity (1 mg ml(-1), 95%) than glabranin (1) (1 mg ml(-1), 74%), whilst umbelliferone (2) and scopoletin (3) were slightly pro-oxidant. PMID:23561082

  9. Prenylated polyphenolic compounds from Glycyrrhiza iconica and their antimicrobial and antioxidant activities.

    PubMed

    Kırmızıbekmez, Hasan; Uysal, Görkem Berk; Masullo, Milena; Demirci, Fatih; Bağcı, Yavuz; Kan, Yüksel; Piacente, Sonia

    2015-06-01

    A new prenylated isoflavan, iconisoflavan (1), and a new prenylated isoflav-3-ene, iconisoflaven (2) were isolated from the roots of Glycyrrhiza iconica together with four known ones namely (3S)-licoricidin (3), licorisoflavan A (4), topazolin (5) and glycycoumarin (6). The structures were elucidated on the basis of extensive spectroscopic analysis including 1D and 2D NMR as well as HR-MS. Furthermore, the absolute configurations of compounds 1, 3 and 4 were established by electronic circular dichroism (ECD). All the isolated compounds (1-6) were evaluated for their in vitro antimicrobial activities against five pathogenic bacteria and one yeast (Candida albicans) using an in vitro microdilution method. Compounds 1 and 3-5 displayed significant activity against Salmonella typhimurium ATCC 13311 with MIC values ranging from 2 to 8 μg/mL. Additionally, all compounds were screened for their in vitro free radical scavenging activities using an in vitro microdilution DPPH assay spectrofotometrically. The tested compounds exhibited IC50 values in the range of 0.18-0.56 mg/mL, suggesting an activity comparable with that of ascorbic acid (IC50: 0.07 mg/mL). To the best of our knowledge, the present study constitutes the first phytochemical and bioactivity investigation on G. iconica. PMID:25963162

  10. Antioxidant and anti-acetylcholinesterase activities of extracts and secondary metabolites from Acacia cyanophylla

    PubMed Central

    Ghribia, Lotfi; Ghouilaa, Hatem; Omrib, Amel; Besbesb, Malek; Janneta, Hichem Ben

    2014-01-01

    Objective To investigate the antioxidant potential and anti-acetycholinesterase activity of compounds and extracts from Acacia cyanophylla (A. cyanophylla). Methods Three polyphenolic compounds were isolated from ethyl acetate extract of A. cyanophylla flowers. They have been identified as isosalipurposide 1, quercetin 2 and naringenin 3. Their structures were elucidated by extensive spectroscopic methods including 1D and 2D NMR experiments as well as ES-MS. The prepared extracts and the isolated compounds 1-3 were tested for their antioxidant activity using 1′-1′-diphenylpicrylhydrazyl (DPPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) scavenging assays and reducing power. They have been also investigated for inhibitory effect against acetylcholinesterase using the microplate assay. Results In the DPPH test, the EtOAc extract of flowers exhibited the highest antioxidant effect (67.26 µg/mL). Isosalipurposide 1 showed a significant antiradical power against DPPH (81.9 µg/mL). All extracts showed a dose-dependent acetylcholinesterase inhibition. In terms of the IC50 value, the butanolic extract (16.03 µg/mL) was the most potent sample. Isosalipurposide 1 was found to be active against AChE with an IC50 value of 52.04 µg/mL. Conclusions The results demonstrated the important antioxidant and anti-acetylcholinesterase activity of pure compounds and extracts from A. cyanophylla. PMID:25183120

  11. Cardamonin, inhibits pro-inflammatory mediators in activated RAW 264.7 cells and whole blood.

    PubMed

    Ahmad, Syahida; Israf, Daud A; Lajis, Nordin Hj; Shaari, Khozirah; Mohamed, Habsah; Wahab, Afiza A; Ariffin, Khaizurin T; Hoo, Wei Yee; Aziz, Nasaruddin A; Kadir, Arifah A; Sulaiman, Mohamad R; Somchit, Muhammad N

    2006-05-24

    Some chalcones, such as hydroxychalcones have been reported previously to inhibit major pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha) and reactive oxygen species production by suppressing inducible enzyme expression via inhibition of the mitogen-activated protein kinase (MAPK) pathway and nuclear translocation of critical transcription factors. In this report, the effects of cardamonin (2',4'-dihydroxy-6'-methoxychalcone), a chalcone that we have previously isolated from Alpinia rafflesiana, was evaluated upon two cellular systems that are repeatedly used in the analysis of anti-inflammatory bioactive compounds namely RAW 264.7 cells and whole blood. Cardamonin inhibited NO and PGE(2) production from lipopolysaccharide- and interferon-gamma-induced RAW cells and whole blood with IC(50) values of 11.4 microM and 26.8 microM, respectively. Analysis of thromboxane B(2) (TxB(2)) secretion from whole blood either stimulated via the COX-1 or COX-2 pathway revealed that cardamonin inhibits the generation of TxB(2) via both pathways with IC(50) values of 2.9 and 1.1 microM, respectively. Analysis of IC(50) ratios determined that cardamonin was more COX-2 selective in its inhibition of TxB(2) with a ratio of 0.39. Cardamonin also inhibited the generation of intracellular reactive oxygen species and secretion of TNF-alpha from RAW 264.7 cells in a dose responsive manner with IC(50) values of 12.8 microM and 4.6 microM, respectively. However, cardamonin was a moderate inhibitor of lipoxygenase activity when tested in an enzymatic assay system, in which not a single concentration tested was able to cause an inhibition of more than 50%. Our results suggest that cardamonin acts upon major pro-inflammatory mediators in a similar fashion as described by previous work on other closely related synthetic hydroxychalcones and strengthens the conclusion of the importance of the methoxyl moiety substitution on

  12. Effect of etizolam (Depas) on production of superoxide anion by platelet-activating factor and N-formyl-methionyl-leucyl-phenylalanine-stimulated guinea pig polymorphonuclear leukocytes.

    PubMed

    Aratani, H; Nishida, Y; Terasawa, M; Maruyama, Y

    1988-06-01

    Effect of etizolam on platelet activating factor (PAF) and N-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced superoxide anion (O2-) production in guinea pig polymorphonuclear leukocytes (PMNL) was investigated. Etizolam showed the inhibitory effect on PAF-induced O2- production concentration dependently, with an IC50 value of 4.7 microM, but it had no inhibitory effect on FMLP-induced O2- production at 100 microM. These results suggest that etizolam has a selectively strong inhibitory effect on PAF-induced O2- production in guinea pig PMNL. PMID:2848961

  13. An NMR Biochemical Assay for Fragment-Based Drug Discovery: Evaluation of an Inhibitor Activity on Spermidine Synthase of Trypanosoma cruzi.

    PubMed

    Yamasaki, Kazuhiko; Tani, Osamu; Tateishi, Yukihiro; Tanabe, Eiki; Namatame, Ichiji; Niimi, Tatsuya; Furukawa, Koji; Sakashita, Hitoshi

    2016-03-10

    Although NMR in fragment-based drug discovery is utilized almost exclusively to evaluate physical binding between molecules, it should be also a powerful tool for biochemical assay, evaluating inhibitory effect of compounds on enzymatic activity. Time-dependent spectral change in real-time monitoring or inhibitor concentration-dependent spectral change after constant-time reaction was processed by factor analysis, by which reaction rate or IC50 value was obtained. Applications to spermidine synthase of Trypanosoma cruzi, which causes Chagas disease, are described. PMID:26881725

  14. Isolation and Characterization of Dammarane-Type Saponins from Gynostemma pentaphyllum and Their Inhibitory Effects on IL-6-Induced STAT3 Activation.

    PubMed

    Lee, Chul; Lee, Jin Woo; Jin, Qinghao; Jang, Hari; Jang, Hyun-Jae; Rho, Mun-Chual; Lee, Myung Koo; Lee, Chong Kil; Lee, Mi Kyeong; Hwang, Bang Yeon

    2015-05-22

    Five new dammarane-type saponins, gypenosides GD1-GD5 (1-5), along with six known saponins (6-11), were isolated from the aerial parts of Gynostemma pentaphyllum using various chromatographic methods. Their structures were elucidated by a combination of spectroscopic and spectrometric data, including 1D and 2D NMR and HRESIMS. All isolates were tested for their inhibitory effects on IL-6-induced STAT3 promoter activity in Hep3B cells. Compounds 1, 9, and 11 displayed potent inhibitory effects, with IC50 values ranging from 0.27 to 0.59 μM. PMID:25895106

  15. Total Phenolic Content and Antioxidant Activity of Some Malvaceae Family Species

    PubMed Central

    de Oliveira, Adriana Maria Fernandes; Pinheiro, Lilian Sousa; Pereira, Charlane Kelly Souto; Matias, Wemerson Neves; Gomes, Roosevelt Albuquerque; Chaves, Otemberg Souza; de Souza, Maria de Fátima Vanderlei; de Almeida, Reinaldo Nóbrega; de Assis, Temilce Simões

    2012-01-01

    The antioxidant activity of four species of the Malvaceae family (Sidastrum micranthum (A. St.-Hil.) Fryxell, Wissadula periplocifolia (L.) C. Presl, Sida rhombifolia (L.) E. H. L and Herissantia crispa L. (Brizicky)) were studied using the total phenolic content, DPPH radical scavenging activity and Trolox equivalent antioxidant capacity (TEAC) assays. The antioxidant activity of the crude extract, phases and two isolated flavonoids, kaempferol 3,7-di-O-α-L-rhamnopyranoside (lespedin) and kaempferol 3-O-β-D-(6''-E-p-coumaroil) glucopyranoside (tiliroside) was determined. The results showed that there is a strong correlation between total polyphenol contents and antioxidant activity of the crude extract of Sidastrum micranthum and Wissadula periplocifolia; however, this was not observed between Sida rhombifolia and Herissantia crispa. The ethyl acetate (EaF) phase showed the best antioxidant effect in the total phenolics, DPPH and TEAC assays, followed by the chloroform (CfF) phase, in most species tested. Lespedin, isolated from the EaF phase of W. periplocifolia and H. crispa may not be responsible for the antioxidant activity due to its low antioxidant activity (IC50: DPPH: 1,019.92 ± 68.99 mg/mL; TEAC: 52.70 ± 0.47 mg/mL); whereas tiliroside, isolated from W. periplocifolia, H. crispa and S. micrantum presented a low IC50 value (1.63 ± 0.86 mg/mL) compared to ascorbic acid in the TEAC assay. PMID:26787614

  16. Antipsoriatic activity and cytotoxicity of ethanolic extract of Nigella sativa seeds

    PubMed Central

    Dwarampudi, Lalitha Priyanka; Palaniswamy, Dhanabal; Nithyanantham, Muruganantham; Raghu, P. S.

    2012-01-01

    Background: Nigella sativa Linn (Ranunculaceae) is popularly known as black cumin with a wide spectrum of pharmacological activities including anti-inflammatory, antibacterial, antifungal and antihelmenthic. The seeds are externally applied for eruptions of skin. The seeds are used traditionally for psoriasis tropicus with general pain and eruption of patches. Objective: The ethanolic extract of Nigella sativa seeds were evaluated for antipsoriatic activity. Materials and Methods: The screening of antipsoriatic activity of 95% of ethanolic extract of Nigella sativa seeds by using mouse tail model for psoriasis and in vitro antipsoriatic activity was carried out by SRB Assay using HaCaT human keratinocyte cell lines. Results: The ethanolic extract of Nigella sativa seeds extract produced a significant epidermal differentiation, from its degree of orthokeratosis (71.36±2.64) when compared to the negative control (17.30±4.09%). This was equivalent to the effect of the standard positive control, tazarotene (0.1%) gel, which showed a (90.03±2.00%) degree of orthokeratosis. The 95% ethanolic extract of Nigella sativa shown IC50 239 μg/ml, with good antiproliferant activity compared to Asiaticoside as positive control which showed potent activity with IC50 value of 20.13 μg/ml. Conclusion: The ethanolic extract of Nigella sativa seeds also showed increase in relative epidermal thickness when compared to control group by confirming its traditional use in psoriasis treatment. PMID:24082629

  17. Antimicrobial and Antileishmanial Activities of Diterpenoids Isolated from the Roots of Salvia deserta.

    PubMed

    Búfalo, Jennifer; Cantrell, Charles L; Jacob, Melissa R; Schrader, Kevin K; Tekwani, Babu L; Kustova, Tatyana S; Ali, Abbas; Boaro, Carmen S F

    2016-01-01

    Four diterpenes with biological activity were isolated from Salvia deserta roots. Taxodione was considered leishmanicidal with an IC50 value of 1.46 µM (0.46 mg/L) against Leishmania donovani and also exhibited antifungal and antimicrobial activities. Ferruginol displayed the greatest activity [24-h IC50 of 4.5 µM (1.29 mg/L)] against the fish pathogenic bacteria Streptococcus iniae. The crude extract fraction that contained the isolated compounds 7-O-acetylhorminone and horminone showed stronger in vitro antibacterial activity (1.3 mg/L for Staphylococcus aureus and 1.1 mg/L for methicillin-resistant S. aureus) than the compounds tested alone. 7-O-Acetylhorminone and horminone exhibited a synergistic effect against methicillin-resistant S. aureus (FIC of 0.2), and horminone had better activity against S. aureus with respect to other compounds isolated from S. deserta roots. In larvicidal bioassays, these extracts and isolated pure compounds did not show any activity at the highest dose of 125 mg/L against 1-d-old Aedes aegypti larvae. PMID:26308356

  18. Angiotensin-converting enzyme inhibitory effects by plant phenolic compounds: a study of structure activity relationships.

    PubMed

    Al Shukor, Nadin; Van Camp, John; Gonzales, Gerard Bryan; Staljanssens, Dorien; Struijs, Karin; Zotti, Moises J; Raes, Katleen; Smagghe, Guy

    2013-12-01

    In this study, 22 phenolic compounds were investigated to inhibit the angiotensin-converting enzyme (ACE). Tannic acid showed the highest activity (IC50 = 230 μM). The IC50 values obtained for phenolic acids and flavonoids ranged between 0.41 and 9.3 mM. QSAR analysis confirmed that the numbers of hydroxyl groups on the benzene ring play an important role for activity of phenolic compounds and that substitution of hydroxyl groups by methoxy groups decreased activity. Docking studies indicated that phenolic acids and flavonoids inhibit ACE via interaction with the zinc ion and this interaction is stabilized by other interactions with amino acids in the active site. Other compounds, such as resveratrol and pyrogallol, may inhibit ACE via interactions with amino acids at the active site, thereby blocking the catalytic activity of ACE. These structure-function relationships are useful for designing new ACE inhibitors and potential blood-pressure-lowering compounds based on phenolic compounds. PMID:24219111

  19. Chemical constituents from Sonneratia ovata Backer and their in vitro cytotoxicity and acetylcholinesterase inhibitory activities.

    PubMed

    Nguyen, Thi-Hoai-Thu; Pham, Huu-Viet-Thong; Pham, Nguyen-Kim-Tuyen; Quach, Ngo-Diem-Phuong; Pudhom, Khanitha; Hansen, Poul Erik; Nguyen, Kim-Phi-Phung

    2015-06-01

    Sonneratia ovata Backer, Sonneratiaceae, is a widespread plant in mangrove forests in Vietnam, Cambodia, Thailand, Indonesia. Sonneratia ovata's chemical composition remains mostly unknown. Therefore, we now report on the structural elucidation of three new phenolics, sonnerphenolic A (1), sonnerphenolic B (2), and sonnerphenolic C (23), a new cerebroside, sonnercerebroside (3) together with nineteen known compounds, including nine lignans (5-13), two steroids (14, 15), two triterpenoids (16, 17), three gallic acid derivatives (18-20), two phenolic derivatives (4, 22) and a 1-O-benzyl-β-d-glucopyranose (21) isolated from the leaves of Sonneratia ovata. Their chemical structures were established by spectroscopic data, as well as high resolution mass spectra and comparison with literature data. The in vitro acetylcholinesterase (AChE) inhibition and cytotoxic activities against HeLa (human epithelial carcinoma), NCI-H460 (human lung cancer), MCF-7 (human breast cancer) cancer cell lines and PHF (primary human fibroblast) cell were evaluated on some extracts and purified compounds at a concentration of 100 μg/mL. Compounds (5, 6, 23) exhibited cytotoxicity against the MCF-7 cell line with the IC50 values of 146.9±9.0, 114.5±7.2, and 112.8±9.4 μM, respectively, while they showed nontoxic with the normal cell (PHF) with IC50s >277 μM. Among 15 tested compounds, (S)-rhodolatouchol (22) showed inhibition against AChE with an IC50 value of 96.1±14.5 μM. PMID:25933595

  20. Polyvalent effect enhances diglycosidic antiplasmodial activity.

    PubMed

    Zhang, Wen-Qiang; He, Yun; Yu, Qun; Liu, Hai-Peng; Wang, De-Min; Li, Xiao-Bin; Luo, Jian; Meng, Xin; Qin, Hai-Juan; Lucchi, Naomi W; Udhayakumar, Venkatachalam; Iyer, Suri S; Yang, Yang; Yu, Peng

    2016-10-01

    An efficient and facile total synthesis of diglycoside Matayoside D isolated from the root bark of Matayba guianensis with antiplasmodial activity have been accomplished in 11 steps with 5% overall yields starting from commercially available glucose and rhamnose. Furthermore, a class of the diglycosidic derivatives with different lengths of the linker and valences were also prepared and evaluated for their antiplasmodial activities against chloroquine-susceptible (3D7) and chloroquine-resistant (W2) strains of Plasmodium falciparum. Low valent and short linker attached diglycoside show no enhancement of the antiplasmodial activity while polyvalent conjugates showed enhanced antiplasmodial activity with IC50 value at least 20 fold better than that of the corresponding diglycosidic monomer. The polyvalent diglycoside were non-cytotoxic against normal mammalian cells under 50,000 μg/L. PMID:27318984

  1. Characterization of Neuraminidase Inhibitors in Korean Papaver rhoeas Bee Pollen Contributing to Anti-Influenza Activities In Vitro.

    PubMed

    Lee, In-Kyoung; Hwang, Byung Soon; Kim, Dae-Won; Kim, Ji-Yul; Woo, E-Eum; Lee, Yoon-Ju; Choi, Hwa Jung; Yun, Bong-Sik

    2016-04-01

    The active constituents of Korean Papaver rhoeas bee pollen conferring neuraminidase inhibitory activities (H1N1, H3N2, and H5N1) were investigated. Six flavonoids and one alkaloid were isolated and characterized by nuclear magnetic resonance and mass spectrometry data. These included kaempferol-3-sophoroside (1), kaempferol-3-neohesperidoside (2), kaempferol-3-sambubioside (3), kaempferol-3-glucoside (4), quercetin-3-sophoroside (5), luteolin (6), and chelianthifoline (7). All compounds showed neuraminidase inhibitory activities with IC50 values ranging from 10.7 to 151.1 µM. The most potent neuraminidase inhibitor was luteolin, which was the dominant content in the ethyl acetate fraction. All tested compounds displayed noncompetitive inhibition of H3N2 neuraminidase. Furthermore, compounds 1-7 all reduced the severity of virally induced cytopathic effects as determined by the Madin-Darby canine kidney cell-based assay showing antiviral activity with IC50 values ranging from 10.7 to 33.4 µM (zanamivir: 58.3 µM). The active compounds were quantified by high-performance liquid chromatography, and the total amount of compounds 1-7 made up about 0.592 g/100 g bee pollen, contributing a rich resource of a natural antiviral product. PMID:26848705

  2. Studies on the potential antioxidant properties of Senecio stabianus Lacaita (Asteraceae) and its inhibitory activity against carbohydrate-hydrolysing enzymes.

    PubMed

    Tundis, Rosa; Menichini, Federica; Loizzo, Monica R; Bonesi, Marco; Solimene, Umberto; Menichini, Francesco

    2012-01-01

    This study showed for the first time the antioxidant and hypoglycaemic properties of the methanol, n-hexane and ethyl acetate extracts from Senecio stabianus Lacaita, a plant that belongs to the Asteraceae family. The antioxidant activities were carried out using two different in vitro assays, namely 2,2-diphenyl-1-picrylhydrazyl (DPPH) test and 2,2'-azinobis(3-ethylbenzthiazoline-6-sulphonate) (ABTS) test. The ethyl acetate extract showed the highest activity with inhibitory concentration 50% (IC(50)) values of 35.5 and 32.7 µg mL(-1) on DPPH test and ABTS test, respectively. This activity may be related to a good total phenol and flavonoid content. All extracts were also tested for their potential inhibitory activity of α-amylase and α-glucosidase digestive enzymes. The n-hexane extract exhibited the highest α-amylase inhibition with an IC(50) value of 0.21 mg mL(-1). Through bioassay-guided fractionation processes seven fractions (A-G) were obtained and tested. Based on the phytochemical analysis, the activity of n-hexane extract may be related to the presence of monoterpenes and sesquiterpenes. PMID:21644170

  3. New SIRT1 activator from alkaline hydrolysate of total saponins in the stems-leaves of Panax ginseng.

    PubMed

    Ma, Li-Yuan; Zhou, Qi-Le; Yang, Xiu-Wei

    2015-11-15

    Two new dammarane-type triterpenes, namely ginsenoslaloside-I [3β,12β,24S-trihydroxy-dammara-20(22)E,25-diene-3-O-β-D-glucopyranoside, 1] and 20(S)-ginsenoside-Rh1-6'-acetate (2), together with twelve known compounds (3-14) were isolated from the alkaline hydrolysate of total saponins of the stems-leaves of Panax ginseng C.A. Meyer. Their chemical structures were elucidated by extensive spectroscopic analyses and comparison with the reported data. All 14 compounds were evaluated for their anti-proliferative activities against two human cancer cell lines (HL-60 and Hep-G2) and promotion activities of SIRT1. Compound 6 exhibited significant inhibitory activity in a concentration-dependent manner against HL-60 and Hep-G2 with the IC50 values of 10.32 and 24.33μM, respectively, and had comparable IC50 values with those of vinorelbine, a positive control agent. Meanwhile, compounds 1 and 6 were found to be a potential activator of SIRT1. The preliminary structure-activity relationship was also discussed based on the experimental data obtained. PMID:26420067

  4. In Vitro Inhibition Of Three Different Drugs Used In Rheumatoid Arthritis Treatment On Human Serum Paraoxanase 1 Enzyme Activity.

    PubMed

    Dilek, Esra; Polat, M Fatih

    2016-01-01

    We studied in vitro effects of three different drugs (ibuprofen, meloxicam and methotrexate) which are often used in rheumatoid arthritis (RA) treatment on human serum paraoxanase1 (PON1) enzyme activity. The drugs used in RA treatment decreased the in vitro PON1 activity. The inhibition mechanism of ibuprofen and methotrexate were noncompetitive whereas meloxicam was a competitive inhibitor. The IC50 values for ibuprofen, meloxicam and methotrexate were calculated to be 0.35 mM, 0.10 mM, and 0.18 mM, respectively, and the Ki constants were calculated to be 0.890 mM, 0.125 mM, and 0.260 mM, respectively. The IC50 and Ki values showed the maximum inhibition of meloxicam drugs. We propose a prediction scheme for the interaction of meloxicam with the PON1 active site because we thought that meloxicam interacts with the amino acids which are in the PON1 enzyme active site. The results we found showed that these drugs which are often used in RA treatment in vitro inhibit the activity of the enzyme with different inhibition mechanisms at low doses. PMID:26458405

  5. Impact of Wines and Wine Constituents on Cyclooxygenase-1, Cyclooxygenase-2, and 5-Lipoxygenase Catalytic Activity

    PubMed Central

    Temml, Veronika; Maghradze, David; Vanek, Tomas

    2014-01-01

    Cyclooxygenases and lipoxygenases are proinflammatory enzymes; the former affects platelet aggregation, vasoconstriction, vasodilatation and later the development of atherosclerosis. Red wines from Georgia and central and western Europe inhibited cyclooxygenase-1 (COX-1) activity in the range of 63–94%, cyclooxygenase-2 (COX-2) activity in the range of 20–44% (tested at a concentration of 5 mL/L), and 5-lipoxygenase (5-LOX) activity in the range of 72–84% (at a concentration of 18.87 mL/L). White wines inhibited 5-LOX in the range of 41–68% at a concentration of 18.87 mL/L and did not inhibit COX-1 and COX-2. Piceatannol (IC50 = 0.76 μM) was identified as a strong inhibitor of 5-LOX followed by luteolin (IC50 = 2.25 μM), quercetin (IC50 = 3.29 μM), and myricetin (IC50 = 4.02 μM). trans-Resveratrol was identified as an inhibitor of COX-1 (IC50 = 2.27 μM) and COX-2 (IC50 = 3.40 μM). Red wine as a complex mixture is a powerful inhibitor of COX-1, COX-2, and 5-LOX, the enzymes involved in eicosanoid biosynthetic pathway. PMID:24976682

  6. Preparation of bioactive peptides with high angiotensin converting enzyme inhibitory activity from winged bean [Psophocarpus tetragonolobus (L.) DC.] seed.

    PubMed

    Wan Mohtar, Wan Abd Al-Qadr Imad; Hamid, Azizah Abdul; Abd-Aziz, Suraini; Muhamad, Sharifah Kharidah Syed; Saari, Nazamid

    2014-12-01

    Winged bean [Psophocarpus tetragonolobus (L.) DC.] seed is a potential underexploited source of vegetable protein due to its high protein content. In the present work, undefatted and defatted winged bean seed hydrolysates, designated as UWBSH and DWBSH, respectively were produced separately by four proteolytic enzymes namely Flavourzyme, Alcalase, Bromelain, and Papain using pH-stat method in a batch reactor. Enzymatic hydrolysis was carried out over a period of 0.5 to 5 h. UWBSH and DWBSH produced were tested for their ACE inhibitory activity in relation to the hydrolysis time and degree of hydrolysis (DH). Maximum ACE inhibitory activity, both for UWBSH and DWBSH, were observed during 3 to 5 h of hydrolysis. Both, UWBSH (DH 91.84 %), and DWSBH (DH 18.72 %), produced by Papain at 5 h hydrolysis, exhibited exceptionally high ACE inhibitory activity with IC50 value 0.064 and 0.249 mg mL(-1), respectively. Besides, papain-produced UWBSH and DWBSH were further fractionated into three fractions based on molecular weight (UWBSH-I, <10 kDa; UWBSH-II, <5 kDa; UWBSH-III, <2 kDa) and (DWBSH-I, <10 kDa; DWBSH-II, <5 kDa; DWBSH-III, <2 kDa). UWBSH-III revealed the highest ACE inhibitory activity (IC50 0.003 mg mL(-1)) compared with DWBSH-III (IC50 0.130 mg mL(-1)). The results of the present investigation revealed that winged bean seed hydrolysates can be explored as a potential source of ACE inhibitory peptides suggesting their uses for physiological benefits as well as for other functional food applications. PMID:25477632

  7. Cholinesterase activity in the tissues of bivalves Noah's ark shell (Arca noae) and warty venus (Venus verrucosa): characterisation and in vitro sensitivity to organophosphorous pesticide trichlorfon.

    PubMed

    Perić, Lorena; Ribarić, Luka; Nerlović, Vedrana

    2013-08-01

    Cholinesterase (ChE, EC 3.1.1.7) activity was investigated in gills and adductor muscle of two bivalve species: Arca noae and Venus verrucosa. The properties of ChEs were investigated using acetylcholine iodide (ASCh), butyrylcholine iodide (BSCh) and propionylcholine iodide (PrSCh) as substrates and eserine, BW254c51 and iso-OMPA as specific inhibitors. The highest level of ChE activity in crude tissue extracts was detected with PrSCh followed by ASCh, while values obtained with BSCh were apparently low, except in A. noae adductor muscle. The enzyme activity in A. noae gills and V. verrucosa gills and adductor muscle was significantly inhibited by BW254c51, but not with iso-OMPA. ChE activity in adductor muscle of A. noae was significantly reduced by both diagnostic inhibitors. The effect of organophosphorous pesticide trichlorfon on ChE activity was investigated in vitro in both species as well as in the gills of mussels Mytilus galloprovincialis. The highest sensitivity of ChE to trichlorfon was observed in A. noae gills and adductor muscle (IC50 1.6×10(-7)M and 1.1×10(-7)M, respectively), followed by M. galloprovincialis gills (IC50 1.0×10(-6)M) and V. verrucosa gills and adductor muscle (IC50 1.7×10(-5)M and 0.9×10(-5)M, respectively). The results of this study suggest the potential of ChE activity measurement in the tissues of A. noae as effective biomarker of OP exposure in marine environment. PMID:23701992

  8. Mathematical Modeling Activities as a Useful Tool for Values Education

    ERIC Educational Resources Information Center

    Doruk, Bekir Kursat

    2012-01-01

    Values education is crucial since it is one of the factors to reach success in education in broader sense and in mathematics education in particular sense. It is also important for educating next generations of societies. However, previous research showed that expected importance for values education was not given in Mathematics courses. In a few…

  9. Cellular uptake and anticancer activity of carboxylated gallium corroles.

    PubMed

    Pribisko, Melanie; Palmer, Joshua; Grubbs, Robert H; Gray, Harry B; Termini, John; Lim, Punnajit

    2016-04-19

    We report derivatives of gallium(III) tris(pentafluorophenyl)corrole, 1 [Ga(tpfc)], with either sulfonic (2) or carboxylic acids (3, 4) as macrocyclic ring substituents: the aminocaproate derivative, 3 [Ga(ACtpfc)], demonstrated high cytotoxic activity against all NCI60 cell lines derived from nine tumor types and confirmed very high toxicity against melanoma cells, specifically the LOX IMVI and SK-MEL-28 cell lines. The toxicities of 1, 2, 3, and 4 [Ga(3-ctpfc)] toward prostate (DU-145), melanoma (SK-MEL-28), breast (MDA-MB-231), and ovarian (OVCAR-3) cancer cells revealed a dependence on the ring substituent: IC50values ranged from 4.8 to >200 µM; and they correlated with the rates of uptake, extent of intracellular accumulation, and lipophilicity. Carboxylated corroles 3 and 4, which exhibited about 10-fold lower IC50values (<20 µM) relative to previous analogs against all four cancer cell lines, displayed high efficacy (Emax= 0). Confocal fluorescence imaging revealed facile uptake of functionalized gallium corroles by all human cancer cells that followed the order: 4 > 3 > 2 > 1 (intracellular accumulation of gallium corroles was fastest in melanoma cells). We conclude that carboxylated gallium corroles are promising chemotherapeutics with the advantage that they also can be used for tumor imaging. PMID:27044076

  10. Bufadienolides with cytotoxic activity from the skins of Bufo bufo gargarizans.

    PubMed

    Li, Bao-Jing; Tian, Hai-Yan; Zhang, Dong-Mei; Lei, Yu-He; Wang, Lei; Jiang, Ren-Wang; Ye, Wen-Cai

    2015-09-01

    Twelve new bufadienolides (1-12), along with fourteen known analogues (13-26) were isolated from the skins of Bufo bufo gargarizans Cantor. Their chemical structures were elucidated on the basis of NMR, HRESIMS and X-ray diffraction analysis. Compound 1 was an unusual bufadienolide with 3,19-epoxy moiety and A/B trans ring junction. Compounds 2-4 were rare bufadienolides possessing 10-H or 10-carboxyl units. All the isolated compounds were tested for their cytotoxic effects on HepG2, A549 and HeLa cells. Six new compounds (2, 3, 5, 6, 10 and 12) displayed significant anti-proliferative activities with IC50 values ranging from 0.049 to 1.856 μM. Arenobufagin (24) exhibited the most potent cytotoxic activity with IC50 value 0.011 μM. In addition, the present data provided more insight into the structure-activity relationships of bufadienolides. PMID:26022446

  11. Inhibitory effects of commonly used herbal extracts on UGT1A1 enzyme activity.

    PubMed

    Mohamed, Mohamed-Eslam F; Tseng, Tiffany; Frye, Reginald F

    2010-10-01

    Commonly used herbal supplements were screened for their potential to inhibit UGT1A1 activity using human liver microsomes. Extracts screened included ginseng, echinacea, black cohosh, milk thistle, garlic, valerian, saw palmetto, and green tea epigallocatechin gallate (EGCG). Estradiol-3-O-glucuronide (E-3-G) formation was used as the index of UGT1A1 activity. All herbal extracts except garlic showed inhibition of UGT1A1 activity at one or more of the three concentrations tested. A volume per dose index (VDI) was calculated to estimate the volume in which the daily dose should be diluted to obtain an IC(50)-equivalent concentration. EGCG, echinacea, saw palmetto, and milk thistle had VDI values >2.0 L per dose unit, suggesting a higher potential for interaction. Inhibition curves were constructed for EGCG, echinacea, saw palmetto, and milk thistle. IC(50) values were (mean ± SE) 7.8 ± 0.9, 211.7 ± 43.5, 55.2 ± 9.2, and 30.4 ± 6.9 µg/ml for EGCG, echinacea, saw palmetto, and milk thistle extracts, respectively. Based on our findings, inhibition of UGT1A1 by milk thistle and EGCG and to a lesser extent by echinacea and saw palmetto is plausible, particularly in the intestine where higher extract concentrations are anticipated. Further clinical studies are warranted. PMID:20666626

  12. Isolation of Bioactive Compounds That Relate to the Anti-Platelet Activity of Cymbopogon ambiguus

    PubMed Central

    Grice, I. Darren; Rogers, Kelly L.; Griffiths, Lyn R.

    2011-01-01

    Infusions and decoctions of Cymbopogon ambiguus have been used traditionally in Australia for the treatment of headache, chest infections and muscle cramps. The aim of the present study was to screen and identify bioactive compounds from C. ambiguus that could explain this plant's anti-headache activity. A dichloromethane extract of C. ambiguus was identified as having activity in adenosine-diphosphate-induced human platelet aggregation and serotonin-release inhibition bioassays. Subsequent fractionation of this extract led to the isolation of four phenylpropenoids, eugenol, elemicin, eugenol methylether and trans-isoelemicin. While both eugenol and elemicin exhibited dose-dependent inhibition of ADP-induced human platelet serotonin release, only eugenol displayed potent inhibitory activity with an IC50 value of 46.6 μM, in comparison to aspirin, with an IC50 value of 46.1 μM. These findings provide evidence to support the therapeutic efficacy of C. ambiguus in the non-conventional treatment of headache and inflammatory conditions. PMID:20047890

  13. Alkaloids from Peumus boldus and their acetylcholinesterase, butyrylcholinesterase and prolyl oligopeptidase inhibition activity.

    PubMed

    Hošt'álková, Anna; Opletal, Lubomír; Kuneš, Jiří; Novák, Zdeněk; Hrabinová, Martina; Chlebek, Jakub; Čegan, Lukáš; Cahlíková, Lucie

    2015-04-01

    Eleven isoquinoline alkaloids (1-11) were isolated from dried leaves of Peumus boldus Mol. by standard chromatographic methods. The chemical structures were elucidated by MS, and 1D and 2D NMR spectroscopic analysis, and by comparison with literature data. Compounds isolated in sufficient amount were evaluated for their acetylcholinesterase, and butyrylcholinesterase inhibition activity using Ellman's method. In the prolyl oligopeptidase assay, Z-Gly-Pro-p-nitroanilide was used as substrate. Promising butyrylcholinesterase inhibition activities were demonstrated by two benzylisoquinoline alkaloids, reticuline (8) and N-methylcoclaurine (9), with IC50 values of 33.6 ± 3.0 µM and 15.0 ± 1.4 µM, respectively. Important prolyl oligopeptidase inhibition activities were shown by N-methyllaurotetanine (6) and sinoacutine (4) with IC50 values of 135.4 ± 23.2 µM and 143.1 ± 25.4 µM, respectively. Other tested compounds were considered inactive. PMID:25973480

  14. Synthesis, structures and urease inhibitory activity of cobalt(III) complexes with Schiff bases.

    PubMed

    Jing, Changling; Wang, Cunfang; Yan, Kai; Zhao, Kedong; Sheng, Guihua; Qu, Dan; Niu, Fang; Zhu, Hailiang; You, Zhonglu

    2016-01-15

    A series of new cobalt(III) complexes were prepared. They are [CoL(1)(py)3]·NO3 (1), [CoL(2)(bipy)(N3)]·CH3OH (2), [CoL(3)(HL(3))(N3)]·NO3 (3), and [CoL(4)(MeOH)(N3)] (4), where L(1), L(2), L(3) and L(4) are the deprotonated form of N'-(2-hydroxy-5-methoxybenzylidene)-3-methylbenzohydrazide, N'-(2-hydroxybenzylidene)-3-hydroxylbenzohydrazide, 2-[(2-dimethylaminoethylimino)methyl]-4-methylphenol, and N,N'-bis(5-methylsalicylidene)-o-phenylenediamine, respectively, py is pyridine, and bipy is 2,2'-bipyridine. The complexes were characterized by infrared and UV-Vis spectra, and single crystal X-ray diffraction. The Co atoms in the complexes are in octahedral coordination. Complexes 1 and 4 show effective urease inhibitory activities, with IC50 values of 4.27 and 0.35 μmol L(-1), respectively. Complex 2 has medium activity against urease, with IC50 value of 68.7 μmol L(-1). While complex 3 has no activity against urease. Molecular docking study of the complexes with Helicobacter pylori urease was performed. PMID:26712097

  15. Chemical constituents and antioxidant and biological activities of the essential oil from leaves of Solanum spirale.

    PubMed

    Keawsa-ard, Sukanya; Liawruangrath, Boonsom; Liawruangrath, Saisunee; Teerawutgulrag, Aphiwat; Pyne, Stephen G

    2012-07-01

    The essential oil of the leaves Solanium spirale Roxb. was isolated by hydrodistillation and analyzed for the first time using GC and GC-MS. Thirty-nine constituents were identified, constituting 73.36% of the total chromatographical oil components. (E)-Phytol (48.10%), n-hexadecanoic acid (7.34%), beta-selinene (3.67%), alpha-selinene (2.74%), octadecanoic acid (2.12%) and hexahydrofarnesyl acetone (2.00%) were the major components of this oil. The antioxidant activity of the essential oil was evaluated by using the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging assay. The oil exhibited week antioxidant activity with an IC50 of 41.89 mg/mL. The essential oil showed significant antibacterial activity against both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus with MIC values of 43.0 microg/mL and 21.5 microg/mL, respectively. It also showed significant cytotoxicity against KB (oral cancer), MCF-7 (breast cancer) and NCI-H187 (small cell lung cancer) with the IC50 values of 26.42, 19.69, and 24.02 microg/mL, respectively. PMID:22908592

  16. Phytochemical analysis and in vitro antiviral activities of the essential oils of seven Lebanon species.

    PubMed

    Loizzo, Monica R; Saab, Antoine M; Tundis, Rosa; Statti, Giancarlo A; Menichini, Francesco; Lampronti, Ilaria; Gambari, Roberto; Cinatl, Jindrich; Doerr, Hans Wilhelm

    2008-03-01

    The chemical composition of the essential oils of Laurus nobilis, Juniperus oxycedrus ssp. oxycedrus, Thuja orientalis, Cupressus sempervirens ssp. pyramidalis, Pistacia palaestina, Salvia officinalis, and Satureja thymbra was determined by GC/MS analysis. Essential oils have been evaluated for their inhibitory activity against SARS-CoV and HSV-1 replication in vitro by visually scoring of the virus-induced cytopathogenic effect post-infection. L. nobilis oil exerted an interesting activity against SARS-CoV with an IC(50) value of 120 microg/ml and a selectivity index (SI) of 4.16. This oil was characterized by the presence of beta-ocimene, 1,8-cineole, alpha-pinene, and beta-pinene as the main constituents. J. oxycedrus ssp. oxycedrus oil, in which alpha-pinene and beta-myrcene were the major constituents, revealed antiviral activity against HSV-1 with an IC(50) value of 200 microg/ml and a SI of 5. PMID:18357554

  17. Synthesis and Antileishmanial Activity of Natural Dehydrodieugenol and Its Mono- and Dimethyl Ethers.

    PubMed

    Rodrigues, Luis Cezar; Barbosa-Filho, José Maria; de Oliveira, Marcia Rosa; do Nascimento Néris, Patrícia Lima; Borges, Flávio Valadares Pereira; Mioso, Roberto

    2016-07-01

    The study of chemistry of naturally occurring compounds and the synthesis of their derivatives is fundamentally important for the development of new drugs. In this work, dehydrodieugenol (DHDE) was obtained through oxidative coupling of eugenol, promoted by an aqueous mixture of potassium ferricyanide (K3 [Fe(CN)6 ]) and NH3  · H2 O. The partial methoxylation of DHDE with MeI and K2 CO3 mainly resulted in the molecular-shaped monomethyl ether (DHDE-1MeO) and its dimethyl ether derivative (DHDE-2MeO). The products from the reactions were characterized by (1) H- and (13) C-NMR spectroscopy. Additionally, these studies have reported the antileishmanial activity of DHDE against Leishmania amazonensis (IC50 value of 42.20 μg ml(-1) ) and shown that partial methoxylation of DHDE results in a significant increase in its antiparasitic activity (IC50 value of 13.68 μg ml(-1) ). Based on in vitro bioassays, DHDE-1MeO has shown the highest leishmanicidal activity in promastigota form. Production by direct one-step synthesis of this monomethoxylated compound can be considered to be a cost-effective and environmentally friendly method with a short reaction time. PMID:27251851

  18. Novel ruthenium(II) cyclopentadienyl thiosemicarbazone compounds with antiproliferative activity on pathogenic trypanosomatid parasites.

    PubMed

    Fernández, Mariana; Arce, Esteban Rodríguez; Sarniguet, Cynthia; Morais, Tânia S; Tomaz, Ana Isabel; Azar, Claudio Olea; Figueroa, Roberto; Diego Maya, J; Medeiros, Andrea; Comini, Marcelo; Helena Garcia, M; Otero, Lucía; Gambino, Dinorah

    2015-12-01

    Searching for new prospective antitrypanosomal agents, three novel Ru(II)-cyclopentadienyl compounds, [Ru(η(5)-C5H5)(PPh3)L], with HL=bioactive 5-nitrofuryl containing thiosemicarbazones were synthesized and characterized in the solid state and in solution. The compounds were evaluated in vitro on the blood circulating trypomastigote form of Trypanosoma cruzi (Dm28c strain), the infective form of Trypanosoma brucei brucei (strain 427) and on J774 murine macrophages and human-derived EA.hy926 endothelial cells. The compounds were active against both parasites with IC50 values in the micromolar or submicromolar range. Interestingly, they are much more active on T. cruzi than previously developed Ru(II) classical and organometallic compounds with the same bioactive ligands. The new compounds showed moderate to very good selectivity towards the parasites in respect to mammalian cells. The global results point at [RuCp(PPh3)L2] (L2=N-methyl derivative of 5-nitrofuryl containing thiosemicarbazone and Cp=cyclopentadienyl) as the most promising compound for further developments (IC50T. cruzi=0.41μM; IC50T. brucei brucei=3.5μM). Moreover, this compound shows excellent selectivity towards T. cruzi (SI>49) and good selectivity towards T. brucei brucei (SI>6). In order to get insight into the mechanism of antiparasitic action, the intracellular free radical production capacity of the new compounds was assessed by ESR. DMPO (5,5-dimethyl-1-pirroline-N-oxide) spin adducts related to the bioreduction of the complexes and to redox cycling processes were characterized. In addition, DNA competitive binding studies with ethidium bromide by fluorescence measurements showed that the compounds interact with this biomolecule. PMID:26275470

  19. Inhibition of Nuclear Transcription Factor-κB and Activation of Peroxisome Proliferator-Activated Receptors in HepG2 Cells by Cucurbitane-Type Triterpene Glycosides from Momordica charantia

    PubMed Central

    Nhiem, Nguyen Xuan; Yen, Pham Hai; Ngan, Nguyen Thi Thanh; Quang, Tran Hong; Kiem, Phan Van; Minh, Chau Van; Tai, Bui Huu; Cuong, Nguyen Xuan; Song, Seok Bean

    2012-01-01

    Abstract Momordica charantia: is used to treat various diseases, including inflammatory conditions. Previous reports indicated that the extract of this plant inhibits activation of nuclear transcription factor-κB (NF-κB) but activates peroxisome proliferator-activated receptor (PPAR). Additionally, cucurbitane-type triterpene glycosides are the main bioactive components of the fruit of M. charantia. Therefore, we investigated the anti-inflammatory activity of 17 cucurbitane-type triterpene glycosides (1–17) isolated from this plant. Their inhibition of NF-κB and activation of PPAR activities in HepG2 cells were measured using luciferase reporter and PPAR subtype transactivation assays. Compounds 6 and 8 were found to inhibit NF-κB activation stimulated by tumor necrosis factor-α (TNFα) in a dose-dependent manner. With 50% inhibition concentration (IC50) values of 0.4 μM, compounds 6 and 8 were more potent inhibitors than the positive control, sulfasalazine (IC50=0.9 μM). Compounds 4, 6, and 8 also inhibited TNFα-induced expressions of inducible nitric oxide synthase and cyclooxygenase-2 mRNA. However, only compound 13 significantly increased PPARγ transactivation. PMID:22248180

  20. Synthesis and anticancer activity of novel 4-morpholino-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives bearing chromone moiety.

    PubMed

    Sun, Chengyu; Chen, Chen; Xu, Shan; Wang, Jianqiang; Zhu, Yan; Kong, Dejia; Tao, Hong; Jin, Mengjia; Zheng, Pengwu; Zhu, Wufu

    2016-08-15

    Herein, we designed and synthesized of a novel series of 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine derivatives bearing chromone moiety (10a-j, 13a-j). All the compounds were evaluated for the IC50 values against five cancer cell lines (A549, PC-3, MCF-7, Hela and HepG2). Seven of the target compounds exhibited moderate to excellent cytotoxicity. For these compounds, we tested their inhibitory activities against mTOR kinase, and four of them were tested their inhibitory activities against PI3Kα kinase in further. The results indicated that the optimized compound 10j showed excellent inhibitory activity and cytotoxicity against mTOR kinase, PI3Kα kinase and five cancer cell lines with IC50 values of 1.1μM, 0.92μM and 8.77-14.3μM. Structure-activity relationships (SARs) and docking studies indicated that the thiopyrano[4,3-d]pyrimidine scaffolds exerted little effect on antitumor activities of target compounds. Substitutions of chromone moiety at C-6 position with carboxyl were benefit to the antitumor activities. PMID:27353887

  1. In vitro antioxidant and hypoglycemic activities of Ethiopian spice blend Berbere.

    PubMed

    Loizzo, Monica R; Di Lecce, Giuseppe; Boselli, Emanuele; Bonesi, Marco; Menichini, Federica; Menichini, Francesco; Frega, Natale Giuseppe

    2011-11-01

    The metal chelating activity, antioxidant properties, and the effect on carbohydrate-hydrolyzing enzymes of Ethiopian spice blend Berbere have been investigated. Berbere contains a total amount of phenols corresponding to 71.3 mg chlorogenic acid equivalent per gram of extract and a total flavonoid content of 32.5 mg quercetin equivalent per gram of extract. An increase of the resistance towards forced oxidation was obtained when Berbere was added to sunflower oil. In order to evaluate the bioactivity of the non-polar constituents, an n-hexane extract was obtained from Berbere. The gas chromatography-mass spectrometry analysis revealed the presence of 19 fatty acids constituents (98.1% of the total oil content). Among them, linoleic acid was the major component (72.0% of the total lipids). The ethanolic extract had the highest ferric-reducing ability power (35.4 μM Fe(II)/g) and DPPH scavenging activity with a concentration giving 50% inhibition (IC(50)) value of 34.8 μg/ml. Moreover, this extract exhibited good hypoglycemic activity against α-amylase (IC(50) = 78.3 μg/ml). In conclusion, Ethiopian spice blend Berbere showed promising antioxidant and hypoglycemic activity via the inhibition of carbohydrate digestive enzymes. These activities may be of interest from functional point of view and for the revalorization of the spice blend in gastronomy also outside the African country. PMID:21599464

  2. Composition of essential oil from Tagetes minuta and its cytotoxic, antioxidant and antimicrobial activities.

    PubMed

    Ali, Nasser A Awadh; Sharopov, Farukh S; Al-Kaf, Ali G; Hill, Gabrielle M; Arnold, Norbert; Al-Sokari, Saeed S; Setzer, William N; Wessjohann, Ludger

    2014-02-01

    The essential oil from the leaves of Tagetes minuta L., growing wild in Yemen, was obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry. A total of 28 compounds were identified representing 74.2% of total oil composition. Major components of the essential oil were (Z)-ocimenone (15.9%), (E)-ocimenone (34.8%), (Z)-beta-ocimene (8.3%), limonene (2.3%), (Z)-tagetone (1.8%), dihydrotagetone (1.4%) and an unidentified dimethylvinylketone derivative (20.6%). The oil showed moderate cytotoxic activity against MCF-7 breast tumor cells, with an IC50 of 54.7 +/- 6.2 microg/mL. In the DPPH radical scavenging assay, T. minuta oil showed potent antiradical activity with an IC50 value of 36 microg/mL. Antimicrobial activity was also investigated on several microorganisms, and the essential oil exhibited high activity against methicillin-resistant Staphylococcus aureus (MRSA) with an inhibition zone of 23 mm. It also exhibited remarkable antifungal activity against Candida albicans with an inhibition zone of 26 mm. PMID:24689306

  3. Cytotoxic Activity of the Methanolic Extract of Turnera diffusa Willd on Breast Cancer Cells

    PubMed Central

    Avelino-Flores, María del Carmen; Cruz-López, María del Carmen; Jiménez-Montejo, Fabiola E.; Reyes-Leyva, Julio

    2015-01-01

    Abstract Turnera diffusa Willd, commonly known as Damiana, is employed in traditional medicine as a stimulant, aphrodisiac, and diuretic. Its leaves and stems are used for flavoring and infusion. Damiana is considered to be safe for medicinal use by the FDA. Pharmacological studies have established the hypoglycemic, antiaromatase, prosexual, estrogenic, antibacterial, and antioxidant activity of T. diffusa. The aim of the present study was to evaluate the possible cytotoxic effect of extracts and organic fractions of this plant on five tumor cell lines (SiHa, C-33, Hep G2, MDA-MB-231, and T-47D) and normal human fibroblasts. The results show that the methanolic extract (TdM) displayed greater activity on MDA-MB-231 breast cancer cells (with an IC50 of 30.67 μg/mL) than on the other cancer cell lines. Four organic fractions of this extract exhibited activity on this cancer cell line. In the most active fraction (F4), two active compounds were isolated, arbutin (1) and apigenin (2). This is the first report of a cytotoxic effect by T. diffusa on cancer cells. The IC50 values suggest that the methanolic extract of T. diffusa has potential as an anticancer therapy. PMID:25299247

  4. Cytotoxic activity of the methanolic extract of Turnera diffusa Willd on breast cancer cells.

    PubMed

    Avelino-Flores, María Del Carmen; Cruz-López, María del Carmen; Jiménez-Montejo, Fabiola E; Reyes-Leyva, Julio

    2015-03-01

    Turnera diffusa Willd, commonly known as Damiana, is employed in traditional medicine as a stimulant, aphrodisiac, and diuretic. Its leaves and stems are used for flavoring and infusion. Damiana is considered to be safe for medicinal use by the FDA. Pharmacological studies have established the hypoglycemic, antiaromatase, prosexual, estrogenic, antibacterial, and antioxidant activity of T. diffusa. The aim of the present study was to evaluate the possible cytotoxic effect of extracts and organic fractions of this plant on five tumor cell lines (SiHa, C-33, Hep G2, MDA-MB-231, and T-47D) and normal human fibroblasts. The results show that the methanolic extract (TdM) displayed greater activity on MDA-MB-231 breast cancer cells (with an IC50 of 30.67 μg/mL) than on the other cancer cell lines. Four organic fractions of this extract exhibited activity on this cancer cell line. In the most active fraction (F4), two active compounds were isolated, arbutin (1) and apigenin (2). This is the first report of a cytotoxic effect by T. diffusa on cancer cells. The IC50 values suggest that the methanolic extract of T. diffusa has potential as an anticancer therapy. PMID:25299247

  5. 5-Lipoxygenase and cyclooxygenase-1 inhibitory active compounds from Atractylodes lancea.

    PubMed

    Resch, M; Steigel, A; Chen, Z L; Bauer, R

    1998-03-01

    Lipophilic extracts of Atractylodes lancea rhizomes exhibited potent inhibitory activities in 5-lipoxygenase [IC50 (5-LOX) = 2.9 micrograms/mL (n-hexane extract)] and cyclooxygenase-1 [IC50 (COX-1) = 30.5 micrograms/mL (n-hexane extract)] enzymatic assays. Bioactivity-guided fractionation of the n-hexane extract led to the isolation of a new compound atractylochromene (1), a potent inhibitor in both test systems [IC50 (5-LOX) = 0.6 microM, IC50 (COX-1) = 3.3 microM]. Also obtained was 2-[(2E)-3,7-dimethyl-2,6-octadienyl]-6-methyl-2,5-cyclohexadiene-1 ,4-dione (2), which showed a selective inhibitory activity against 5-LOX [IC50 (5-LOX) 0.2 microM, IC50 (COX-1) 64.3 microM]. The sesquiterpene atractylon (3) and the coumarin osthol (4) turned out to be moderate but selective 5-lipoxygenase inhibitors. Atractylenolides I (5), II (6), and III (7) showed no significant inhibitory effects for either enzyme. Structures were established by spectral data interpretation. PMID:9544564

  6. Influence of decavanadate on rat synaptic plasma membrane ATPases activity.

    PubMed

    Krstić, Danijela; Colović, Mirjana; Bosnjaković-Pavlović, Nada; Spasojević-De Bire, Anne; Vasić, Vesna

    2009-09-01

    The in vitro influence of decameric vanadate species on Na+/K+-ATPase, plasma membrane Ca2+-ATPase (PMCA)-calcium pump and ecto-ATPase activity, using rat synaptic plasma membrane (SPM) as model system was investigated, whereas the commercial porcine cerebral cortex Na+/K+-ATPase served as a reference. The thermal behaviour of the synthesized decavanadate (V10) has been studied by differential scanning calorimetry and thermogravimetric analysis, while the type of polyvanadate anion was identified using the IR spectroscopy. The concentration-dependent responses to V10 of all enzymes were obtained. The half-maximum inhibitory concentration (IC50) of the enzyme activity was achieved at (4.74 +/- 1.15) x 10(-7) mol/l for SPM Na+/K+-ATPase, (1.30 +/- 0.10) x 10(-6) mol/l for commercial Na+/K+-ATPase and (3.13 +/- 1.70) x 10(-8) mol/l for Ca2+-ATPase, while ecto-ATPase is significantly less sensitive toward V10 (IC50 = (1.05 +/- 0.10) x 10(-4) mol/l) than investigated P-type ATPases. Kinetic analysis showed that V10 inhibited Na+/K+-ATPase by reducing the maximum enzymatic velocity and apparent affinity for ATP (increasing K(m) value), implying a mixed mode of interaction between V10 and P-type ATPases. PMID:20037196

  7. Evaluation of antirotavirus activity of flavonoids.

    PubMed

    Savi, Luciane Anita; Caon, Thiago; de Oliveira, Ana Paula; Sobottka, Andrea Michel; Werner, Wolfgang; Reginatto, Flávio Henrique; Schenkel, Eloir Paulo; Barardi, Célia Regina Monte; Simões, Cláudia Maria Oliveira

    2010-12-01

    Flavonoids are dietary components and the most ubiquitous phenolic compounds found in nature, showing a range of pharmacological activities including antiviral action. This study describes the antiviral screening of 60 different flavones and flavonols against human rotavirus (Wa-1 strain) as well as their cytotoxicity in MA104 cells. Cytotoxicity was investigated by cell morphology assessment and antirotavirus activity by cytopathic effect inhibition. Results were expressed as CC(50) and IC(50), respectively, in order to calculate the selectivity index (SI = CC(50)/IC(50)) of each compound. Structure-activity relationships (SAR) were proposed based on antirotavirus activity. PMID:20659535

  8. Inhibitory effect of six herbal extracts on CYP2C8 enzyme activity in human liver microsomes.

    PubMed

    Albassam, Ahmed A; Mohamed, Mohamed-Eslam F; Frye, Reginald F

    2015-05-01

    1. Herbal supplements widely used in the US were screened for the potential to inhibit CYP2C8 activity in human liver microsomes. The herbal extracts screened were garlic, echinacea, saw palmetto, valerian, black cohosh and cranberry. N-desethylamodiaquine (DEAQ) and hydroxypioglitazone metabolite formation were used as indices of CYP2C8 activity. 2. All herbal extracts showed inhibition of CYP2C8 activity for at least one of three concentrations tested. A volume per dose index (VDI) was calculated to determine the volume in which a dose should be diluted to obtain IC50 equivalent concentration. Cranberry and saw palmetto had a VDI value > 5.0 l per dose unit, suggesting a potential for interaction. 3. Inhibition curves were constructed and the IC50 (mean ± SE) values were 24.7 ± 2.7 μg/ml for cranberry and 15.4 ± 1.7 μg/ml for saw palmetto. 4. The results suggest a potential for cranberry or saw palmetto extracts to inhibit CYP2C8 activity. Clinical studies are needed to evaluate the significance of this interaction. PMID:25430798

  9. Trypsin Isoinhibitors with Antiproliferative Activity toward Leukemia Cells from Phaseolus vulgaris cv “White Cloud Bean”

    PubMed Central

    Sun, Jian; Wang, Hexiang; Ng, Tzi Bun

    2010-01-01

    A purification protocol that comprised ion exchange chromatography on DEAE-cellulose, affinity chromatography on Affi-gel blue gel, ion exchange chromatography on SP-Sepharose, and gel filtration by FPLC on Superdex 75 was complied to isolate two trypsin inhibitors from Phaseolus vulgaris cv “White Cloud Bean”. Both trypsin inhibitors exhibited a molecular mass of 16 kDa and reduced the activity of trypsin with an IC50 value of about 0.6 μM. Dithiothreitol attenuated the trypsin inhibitory activity, signifying that an intact disulfide bond is indispensable to the activity. [Methyl-3H] thymidine incorporation by leukemia L1210 cells was inhibited with an IC50 value of 28.8 μM and 21.5 μM, respectively. They were lacking in activity toward lymphoma MBL2 cells and inhibitory effect on HIV-1 reverse transcriptase and fungal growth when tested up to 100 μM. PMID:20617140

  10. BACE1 and cholinesterase inhibitory activities of Nelumbo nucifera embryos.

    PubMed

    Jung, Hyun Ah; Karki, Subash; Kim, Ji Hye; Choi, Jae Sue

    2015-06-01

    The aim of the present study was to evaluate the comparative anti-Alzheimer's disease (AD) activities of different parts of Nelumbo nucifera (leaves, de-embryo seeds, embryos, rhizomes, and stamens) in order to determine the selectivity and efficient use of its individual components. Anti-AD activities of different parts of N. nucifera were evaluated via inhibitory activities on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) along with scavenging activity on peroxynitrite (ONOO(-)). Among the evaluated parts of N. nucifera, the embryo extract exhibited significant inhibitory potential against BACE1 and BChE as well as scavenging activity against ONOO(-). Thus, the embryo extract was selected for detailed investigation on anti-AD activity using BACE1- and ChEs-inhibitory assays. Among the different solvent-soluble fractions, the dichloromethane (CH2Cl2), ethyl acetate (EtOAc), and n-butanol (n-BuOH) fractions showed promising ChEs and BACE1 inhibitory activities. Repeated column chromatography of the CH2Cl2, EtOAc and n-BuOH fractions yielded compounds 1-5, which were neferine (1), liensinine (2), vitexin (3), quercetin 3-O-glucoside (4) and northalifoline (5). Compound 2 exhibited potent inhibitory activities on BACE1, AChE, and BChE with respective IC50 values of 6.37 ± 0.13, 0.34 ± 0.02, and 9.96 ± 0.47 µM. Likewise, compound 1 showed potent inhibitory activities on BACE1, AChE, and BChE with IC50 values of 28.51 ± 4.04, 14.19 ± 1.46, and 37.18 ± 0.59 µM, respectively; the IC50 values of 3 were 19.25 ± 3.03, 16.62 ± 1.43, and 11.53 ± 2.21 µM, respectively. In conclusion, we identified potent ChEs- and BACE1-inhibitory activities of N. nucifera as well as its isolated constituents, which may be further explored to develop therapeutic and preventive agents for AD and oxidative stress related diseases. PMID:25300425

  11. Protein tyrosine phosphatase 1B inhibitory activity of Indonesian herbal medicines and constituents of Cinnamomum burmannii and Zingiber aromaticum.

    PubMed

    Saifudin, Azis; Kadota, Shigetoshi; Tezuka, Yasuhiro

    2013-04-01

    We screened water and methanol extracts of 28 Indonesian medicinal plants for their protein tyrosine phosphatase 1B (PTP1B) inhibitory activities. Nine water extracts, i.e., Alstonia scholaris leaf, Blumea balsamifera, Cinnamomum burmannii, Cymbopogon nardus, Melaleuca leucadendra, Phyllanthus niruri, Piper nigrum, Syzygium aromaticum, and Sy. polyanthum, exhibited ≥70 % inhibition at 25 μg/mL, whereas 11 methanol extracts, i.e., Als. scholaris, Andrographis paniculata, B. balsamifera, Ci. burmannii, Curcuma heyneana, Glycyrrhiza glabra, M. leucadendra, Punica granatum, Rheum palmatum, Sy. polyanthum, and Z. aromaticum, exhibited ≥70 % inhibition at 25 μg/mL. Water extracts of B. balsamifera (IC50, 2.26 μg/mL) and M. leucadendra (IC50, 2.05 μg/mL), and methanol extracts of Ci. burmannii (IC50, 2.47 μg/mL), Pu. granatum (IC50, 2.40 μg/mL), and Sy. polyanthum (IC50, 1.03 μg/mL) exhibited strong inhibitory activity, which was comparable with that of the positive control, RK-682 (IC50, 2.05 μg/mL). The PTP1B inhibitory activity of the constituents of Ci. burmannii and Z. aromaticum was then evaluated. 5'-Hydroxy-5-hydroxymethyl-4″,5″-methylenedioxy-1,2,3,4-dibenzo-1,3,5-cycloheptatriene (2; IC50, 29.7 μM) and trans-cinnamaldehyde (5; IC50, 57.6 μM) were the active constituents of Ci. burmannii, while humulatrien-5-ol-8-one (21; IC50, 27.7 μM), kaempferol-3,4'-di-O-methyl ether (32; IC50, 17.5 μM), and (S)-6-gingerol (33; IC50, 28.1 μM) were those of Z. aromaticum. These results suggest that these medicinal plants may contribute to the treatment and/or prevention of type II diabetes and/or obesity through PTP1B inhibition. PMID:22645080

  12. Chemical composition and antibacterial activity of essential oil and extracts of Citharexylum spinosum flowers from Thailand.

    PubMed

    Mar, Ae; Pripdeevech, Patcharee

    2014-05-01

    The chemical composition and antibacterial and antioxidant activities of the essential oil and various solvent extracts of Citharexylum spinosum flowers are reported. The chemical compositions were determined by GC-MS with 151 volatile constituents identified. Methyl benzoate, piperitone, maltol, and maple furanone were the major constituents. All extracts were tested for their antibacterial activity against eight microorganisms. The flower oil had the greatest antibacterial activity against all bacterial strains (MIC values of 31.2 microg/mL), while the other solvent extracts had MIC values ranging from 31.2 to 1000 microg/mL. The essential oil had the highest antioxidant activity and total phenol content with IC50 values of 62.7 and 107.3 microg/mL, respectively. PMID:25026728

  13. An Empirical Development of Critical Value Factors (CVF) of Online Learning Activities: An Application of Activity Theory and Cognitive Value Theory

    ERIC Educational Resources Information Center

    Levy, Yair

    2008-01-01

    According to activity theory, activities are at the center of human behavior. Extensive attention has been given in literature to the success and effectiveness of online learning programs. Value theory suggests that human perceived value is a critical construct in investigating what is important to individuals. However, very limited attention has…

  14. Antioxidant property and [Formula: see text]-glucosidase, [Formula: see text]-amylase and lipase inhibiting activities of Flacourtia inermis fruits: characterization of malic acid as an inhibitor of the enzymes.

    PubMed

    Alakolanga, A G A W; Kumar, N Savitri; Jayasinghe, Lalith; Fujimoto, Yoshinori

    2015-12-01

    Flacourtia inermis Roxb. (Flacourtiaceae), is a moderate sized tree cultivated in Sri Lanka for its fruits known as Lovi. The current study was undertaken to study the biological activity of extracts of the fruits in an attempt to increase the value of the under exploited fruit crops. Fruits of F. inermis were found to be rich in phenolics and anthocyanins. Polyphenol content of the fruits was determined to be 1.28 g gallic acid equivalents per 100 g of fresh fruit and anthocyanin content was estimated as 108 mg cyanidin-3-glucoside equivalents per 100 g of fresh fruits. The EtOAc extract showed moderate antioxidant activity in the DPPH radical scavenging assay with IC50 value of 66.2 ppm. The EtOAc and MeOH extracts of the fruits also exhibited inhibitory activities toward α-glucosidase, α-amylase and lipase enzymes with IC50values ranging from 549 to 710 ppm, 1021 to 1949 ppm and 1290 to 2096 ppm, respectively. The active principle for the enzyme inhibition was isolated through activity-guided fractionation and was characterized as (S)-malic acid. The results of this study indicate that F. inermis fruits have the potential to be used in health foods and in nutritional supplements. PMID:26604419

  15. Isolation of a ribonuclease with antiproliferative and HIV-1 reverse transcriptase inhibitory activities from Japanese large brown buckwheat seeds.

    PubMed

    Yuan, Susu; Yan, Juan; Ye, Xiujuan; Wu, Zujian; Ng, Tzibun

    2015-03-01

    A ribonuclease, with a molecular mass of 22.5 kDa and an N-terminal sequence exhibiting resemblance to previously isolated buckwheat storage proteins and allergens, was isolated from Japanese large brown buckwheat seeds. The ribonuclease was purified using a simple protocol that comprised ion exchange chromatography on Q-Sepharose and DEAE-cellulose and gel filtration on Superdex 75. The ribonuclease exhibited low activity toward poly U, lower activity toward poly C, and very low activity toward poly A and poly G. The enzyme was activated upon exposure to 10 mM of Fe(2+) and Zn(2+) ions but was inhibited by Ca(2+), Mg(2+), and Mn(2+) ions at the same concentration. The optimum pH and optimum temperature for the enzyme were pH 9 and 60 °C, respectively. It inhibited proliferation of HepG2 hepatoma and MCF 7 breast cancer cells, with an IC50 value of 79.2 and 63.8 μM, respectively. It potently inhibited HIV-1 reverse transcriptase activity with an IC50 of 48 μM. However, there were no antifungal and mitogenic activities. PMID:25503363

  16. 4,5-Substituted 3-Isoxazolols with Insecticidal Activity Act as Competitive Antagonists of Housefly GABA Receptors.

    PubMed

    Liu, Genyan; Ozoe, Fumiyo; Furuta, Kenjiro; Ozoe, Yoshihisa

    2015-07-22

    The insect GABA receptor (GABAR), which is composed of five RDL subunits, represents an important target for insecticides. A series of 4,5-disubstituted 3-isoxazolols, including muscimol analogues, were synthesized and examined for their activities against four splice variants (ac, ad, bc, and bd) of housefly GABARs expressed in Xenopus oocytes. Muscimol was a more potent agonist than GABA in all four splice variants, whereas synthesized analogues did not exhibit agonism but rather antagonism in housefly GABARs. The introduction of bicyclic aromatic groups at the 4-position of muscimol and the simultaneous replacement of the aminomethyl group with a carbamoyl group at the 5-position to afford six 4-aryl-5-carbamoyl-3-isoxazolols resulted in compounds that exhibited significantly enhanced antagonism with IC50 values in the low micromolar range in the ac variant. The inhibition of GABA-induced currents by 100 μM analogues was approximately 1.5-4-fold greater in the ac and bc variants than in the ad and bd variants. 4-(3-Biphenylyl)-5-carbamoyl-3-isoxazolol displayed competitive antagonism, with IC50 values of 30, 34, 107, and 96 μM in the ac, bc, ad, and bd variants, respectively, and exhibited moderate insecticidal activity against houseflies, with an LD50 value of 5.6 nmol/fly. These findings suggest that these 3-isoxazolol analogues are novel lead compounds for the design and development of insecticides that target the orthosteric site of housefly GABARs. PMID:26120732

  17. Honey shows potent inhibitory activity against the bovine testes hyaluronidase.

    PubMed

    Kolayli, Sevgi; Sahin, Huseyin; Can, Zehra; Yildiz, Oktay; Sahin, Kübra

    2016-08-01

    The purpose of this study was to investigate the anti-hyaluronidase activities of honeys from different botanical origins honeys in order to determine their anti-inflammatory properties. The total phenolic contents, total flavonoids and total tannin levels of six types of honey, chestnut, oak, heather, pine, buckwheat and mixed blossom, were determined. Concentration-related inhibition values were tested turbidimetrically on bovine testis hyaluronidase (BTHase) as IC50 (mg/mL). All honeys exhibited various concentration-dependent degrees of inhibition against BTHase. Inhibition values varied significantly depending on honeys' levels of phenolic contents, flavonoid and tannin. The honeys with the highest anti-hyaluronidase activity were oak, chestnut and heather. In conclusion, polyphenol-rich honeys have high anti-hyaluronidase activity, and these honeys have high protective and complementary potential against hyaluronidase-induced anti-inflammatory failures. PMID:26076195

  18. Thiazole-based nitrogen mustards: Design, synthesis, spectroscopic studies, DFT calculation, molecular docking, and antiproliferative activity against selected human cancer cell lines

    NASA Astrophysics Data System (ADS)

    Łączkowski, Krzysztof Z.; Świtalska, Marta; Baranowska-Łączkowska, Angelika; Plech, Tomasz; Paneth, Agata; Misiura, Konrad; Wietrzyk, Joanna; Czaplińska, Barbara; Mrozek-Wilczkiewicz, Anna; Malarz, Katarzyna; Musioł, Robert; Grela, Izabela

    2016-09-01

    Synthesis, characterization and investigation of antiproliferative activity of ten thiazole-based nitrogen mustard against human cancer cells lines (MV4-11, A549, MCF-7 and HCT116) and normal mouse fibroblast (BALB/3T3) is presented. The structures of novel compounds were determined using 1H and 13C NMR, FAB(+)-MS, and elemental analyses. Among the derivatives, 5b, 5c, 5e, 5f and 5i were found to exhibit high activity against human leukaemia MV4-11 cells with IC50 values of 2.17-4.26 μg/ml. The cytotoxic activity of compound 5c and 5f against BALB/3T3 cells is up to 20 times lower than against cancer cell lines. Our results also show that compounds 5e and 5i have very strong activity against MCF-7 and HCT116 with IC50 values of 3.02-4.13 μg/ml. Moreover, spectroscopic characterization and cellular localization for selected compound were performed. In order to identify potential drug targets we perform computer simulations with DNA-binding site of hTopoI and hTopoII and quantum chemical calculation of interaction and binding energies in complexes of the five most active compounds with guanine.

  19. Synthesis and QSAR study of novel 6-chloro-3-(2-Arylmethylene-1-methylhydrazino)-1,4,2-benzodithiazine 1,1-dioxide derivatives with anticancer activity.

    PubMed

    Sławiński, Jarosław; Żołnowska, Beata; Brzozowski, Zdzisław; Kawiak, Anna; Belka, Mariusz; Bączek, Tomasz

    2015-01-01

    A series of new 6-chloro-3-(2-arylmethylene-1-methylhydrazino)-1,4,2-benzodithiazine 1,1-dioxide derivatives were effectively synthesized from N-methyl-N-(6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)hydrazines. The intermediate compounds as well as the products, were evaluated for their cytotoxic effects toward three human cancer cell lines. All compounds shown moderate or weak cytotoxic effects against the tested cancer cell lines, but selective cytotoxic effects were observed. Compound 16 exhibited the most potent cytotoxic activity against the HeLa cell line, with an IC50 value of 10 µM, while 14 was the most active against the MCF-7 and HCT-116 cell lines, affording IC50 values of 15 µM and 16 µM, respectively. The structure-activity relationship was evaluated based on QSAR methodology. The QSAR MCF-7 model indicated that natural charge on carbon atom C13 and energy of highest occupied molecular orbital (HOMO) are highly involved in cytotoxic activity against MCF-7 cell line. The cytotoxic activity of compounds against HCT-116 cell line is dependent on natural charge on carbon atom C13 and electrostatic charge on nitrogen atom N10. The obtained QSAR models could provide guidelines for further development of novel anticancer agents. PMID:25834988

  20. Investigation of local anesthetic and antimycobacterial activity of Ottonia martiana Miq. (Piperaceae).

    PubMed

    Cunico, Miriam M; Trebien, Herbert A; Galetti, Fábio C; Miguel, Obdulio G; Miguel, Marilis D; Auer, Celso G; Silva, Célio L; de Souza, Ana Olívia

    2015-01-01

    Ottonia martiana is a plant popularly known in Brazil by the use for toothache. Ethanolic extract (EE), hexane fraction (HF), dichloromethane fraction (DF) and piperovatine obtained from O. martiana were assayed in vitro and in vivo. The acute toxicity of EE was determined, and LD50 values of 164.5 and 65.0 mg/kg by the oral and intraperitoneal routes, respectively, indicated a high toxicity for EE in vivo, explaining its popular use by topical administration only. A local anesthetic-like effect of EE and its fractions was observed in experimental models using pain induction, and such effect involved an analgesic action. The antimycobacterial activity of EE, HF, DF and piperovatine was evaluated against Mycobacterium tuberculosis H37Rv ATCC 27924. EE, HF, DF, and piperovatine showed a potential antimycobacterial effect with MICs of 16.0, 62.0, 62.0 and 8.0 μg/mL, respectively. Piperovatine was more effective than the EE or the other fractions. The selectivity index (SI=IC50/MIC) values calculated for EE, HF, DF and piperovatine based on the MICs and the cytotoxicity against J774 macrophages (IC50 by MTT assay) revealed values of 6.43, 2.34, 1.5 and 9.66, respectively. PMID:26628019

  1. Usnic Acid Derivatives with Cytotoxic and Antifungal Activities from the Lichen Usnea longissima.

    PubMed

    Yu, Xuelong; Guo, Qiang; Su, Guozhu; Yang, Ailin; Hu, Zhongdong; Qu, Changhai; Wan, Zhe; Li, Ruoyu; Tu, Pengfei; Chai, Xingyun

    2016-05-27

    Eight usnic acid derivatives, that is, usenamines A-F (1-6), usone (7), and isousone (8), together with the known (+)-usnic acid (9), were isolated from the lichen Usnea longissima. Their structures were elucidated using 1D and 2D NMR and MS data, and the absolute configurations of compounds 1 and 2 were defined by single-crystal X-ray diffraction analyses. Compounds 1, 2, and 8 showed inhibitory effects on the growth of human hepatoma HepG2 cells with IC50 values of 6.0-53.3 μM compared with methotrexate as the positive control, which had an IC50 value of 15.8 μM. Furthermore, 1 induced apoptosis of HepG2 cells in a dose-dependent manner at concentrations of 0-15.0 μM. The isolated compounds were also evaluated for their antifungal and antibacterial activities, with 7 and 8 exhibiting weak inhibitory effects on fungal Trichophyton rubrum spp. with an MIC value of 41.0 μM. PMID:27186821

  2. 1,2,3,4,6-Pentakis[-O-(3,4,5-trihydroxybenzoyl)]-α,β-D-glucopyranose (PGG) analogs: design, synthesis, anti-tumor and anti-oxidant activities.

    PubMed

    Shaikh, Qurat-Ul-Ain; Yang, Meiting; Memon, Khadim Hussain; Lateef, Mehreen; Na, Du; Wan, Shengbiao; Eric, Deslandes; Zhang, Lijuan; Jiang, Tao

    2016-07-22

    1,2,3,4,6-Pentakis[-O-(3,4,5-trihydroxybenzoyl)]-α,β-D-glucopyranose (PGG) 12 has been reported for its antioxidant activities, where the free OH groups in PGG seem to be critical for activities. To explore PGG-based compounds as chemotherapeutic agents and to analyze the contribution of specific OH groups in PGG for anti-cancer activities, we designed and synthesized a series of 27 benzoic and cinnamic acid analogs of PGG. These analogs were tested for cytotoxicities against two human lung (A549 and H1299) and two human colon (HCT116 and HT29) cancer cell lines. Compound 12 (PGG) had highest cytotoxicities against HCT116 and A549 cells with IC50 of 1.61 µM and 3.02 µM, respectively. In contrast, the compound 16 (1,2,3,4,6-pentakis[-O-(4-hydroxy-3-methoxybenzoyl)]-α,β-D-glucopyranose, PVG) was most effective at killing HT29 and H1299 cells with IC50 of 1.76 µM and 3.65 µM, respectively, indicating the mutual contribution of m-methoxy and p-hydroxy groups to the observed cytotoxicities. Moreover, cinnamic acid analogs were less active than the benzoic acid analogs evidenced by higher IC50 values. Furthermore, in cinnamic acid analogs the hydrogenation of double bond to saturated 2-C side chain enhance the cytotoxicities in all four cell lines. Compounds also possess good anti-oxidant and reducing activities. Compound 12 and 26 show the highest antioxidant and reducing activities. PMID:27196315

  3. Low antiplasmodial activity of alkaloids and amides from the stem bark of Zanthoxylum rubescens (Rutaceae).

    PubMed

    Penali, L; Mulholland, D A; Tano, K D; Cheplogoi, P K; Randrianarivelojosia, M

    2007-06-01

    The stem bark of Zanthoxylum rubescens (syn. Fagara rubescens) is used for treating fevers associated with malaria in the Ivory Coast. Three alkaloids: N-nornitidine, 7,9-dimethoxy-2,3-methylenedioxybenzophenanthridine, and bis[6-5,6-dihydrochelerythrinyl)] ether; and two amides: zanthomamide and lemairamide, were isolated from the stem bark of this plant. These compounds were screened in vitro against the chloroquine-sensitive 3D7 strain and the chloroquine-resistant FCM29 strain of P. falciparum. N-nornitidine was found to be inactive. 7,9-dimethoxy-2,3-methylenedioxybenzophenanthridine, lemairamide and zanthomamide showed weak activity with average IC50 values ranging from 45.6 microM to 149.9 microM. Bis[6-15,6-dihydrochelerythrinyl)] ether was the most active of the tested compounds with mean IC50s of 14.9 +/- 1.4 microM in FCM29 strain and 15.3 +/- 3.4 microM in 3D7 strain (approximately 58 to approximately 1130 times less active than chloroquine respectively). The anti-Plasmodium activities of the tested alkaloids of Z. rubescens were low; and do not encourage the use of this plant as antimalarial. PMID:17645189

  4. Evaluation of phenolic contents and antioxidant activity of various solvent extracts of Sonchus asper (L.) Hill

    PubMed Central

    2012-01-01

    Background Sonchus asper (SA) is traditionally used for the treatment of various ailments associated with liver, lungs and kidneys. This study was aimed to investigate the therapeutic potential of nonpolar (hexane, SAHE; ethyl acetate, SAEE and chloroform, SACE) and polar (methanol, SAME) crude extracts of the whole plant. Methods To achieve these goals, several parameters including free-radical (DPPH•, ABTS•+, H2O2 and •OH) scavenging, iron chelating activity, scavenging of superoxide radicals, total flavonoids and total phenolic content (TPC) were examined. Results The SA extracts presented a remarkable capacity to scavenge all the tested reactive species with IC50 values being found at the μg ⁄ ml level. The SAME was shown to have the highest TPCs while lowest IC50 values for the DPPH•, ABTS•+ radical scavenging capacities and iron chelating scavenging efficiency, moreover, SAME had best activities in scavenging of superoxide radicals and hydrogen peroxide as well as potently scavenged the hydroxyl radicals. Conclusion These results suggest the potential of S. asper as a medicine against free-radical-associated oxidative damage. PMID:22305477

  5. Antioxidant, cholinesterase inhibition activities and essential oil analysis of Nelumbo nucifera seeds.

    PubMed

    Khan, Shahnaz; Khan, Hidayatullah; Ali, Farman; Ali, Nayab; Khan, Fahim Ullah; Khan, Sami Ullah

    2016-06-01

    Nelumbo nucifera seeds' essential oil (EO), crude extract and subsequent fractions were evaluated for their DPPH, ABTS and superoxide anion-free radical scavenging and cholinesterase inhibitory activities. The ethyl acetate fraction and EO showed outstanding antioxidant activities with IC50 values of 191, 450 μg/mL (DPPH), 123, 221 μg/mL (ABTS) and 69, 370 μg/mL (superoxide anion). The ethyl acetate fraction and EO also caused significant inhibition of acetylcholinesterase and butyrylcholinesterase with IC50 values of 70 ± 0.6, 64 ± 0.8 and 75 ± 0.3, 58 ± 0.2, in dose-dependent manner. The first ever gas chromatography-mass spectrometry analysis of the EO obtained from N. nucifera seeds resulted in identification of 19 constituents, mainly comprised of oxygenated sesquiterpenes responsible for their promising bioactivity. The crude and fractions revealed the presence of saponins, flavonoids, steroids, alkaloids, terpenoids and cardiac glycosides in phytochemical investigation. PMID:26212099

  6. Enzymatic modification of chitosan by cinnamic acids: Antibacterial activity against Ralstonia solanacearum.

    PubMed

    Yang, Caifeng; Zhou, Yu; Zheng, Yu; Li, Changlong; Sheng, Sheng; Wang, Jun; Wu, Fuan

    2016-06-01

    This study aimed to identify chitosan polymers that have antibacterial activity against the bacterial wilt pathogen. The chitosan polymers were enzymatically synthesized using chitosan and five cinnamic acids (CADs): caffeic acid (CA), ferulic acid (FA), cinnamic acid (CIA), p-coumaric acid (COA) and chlorogenic acid (CHA), using laccase from Pleurotus ostreatus as a catalyst. The reaction was performed in a phosphate buffered solution under heterogenous reaction conditions. The chitosan derivatives (CTS-g-CADs) were characterized by FT-IR, XRD, TGA and SEM. FT-IR demonstrated that the reaction products bound covalently to the free amino groups or hydroxyl groups of chitosan via band of amide I or ester band. XRD showed a reduced packing density for grafted chitosan comparing to original chitosan. TGA demonstrated that CTS-g-CADs have a higher thermostability than chitosan. Additionally, chitosan and its derivatives showed similar antibacterial activity. However, the IC50 value of the chitosan-caffeic acid derivative (CTS-g-CA) against the mulberry bacterial wilt pathogen RS-5 was 0.23mg/mL, which was two-fifths of the IC50 value of chitosan. Therefore, the enzymatically synthesized chitosan polymers can be used to control plant diseases in biotechnological domains. PMID:26993531

  7. In vitro antiplasmodial activity of callus culture extracts and fractions from fresh apical stems of Phyllanthus niruri L. (Euphorbiaceae): part 2.

    PubMed

    Cimanga, R K; Tona, L; Luyindula, N; Mesia, K; Lusakibanza, M; Musuamba, C T; Apers, S; De Bruyne, T; Van Miert, S; Hermans, N; Totté, J; Pieters, L; Vlietinck, A J

    2004-12-01

    The ethanolic extracts from fresh apical stems of Phyllanthus niruri L. (Euphorbiaceae) cultured on Murashige and Skoog (MS) medium supplemented with IBA/BAP/Coco nucifera L. milk for 1, 2, 4 and 6 months were phytochemically and biologically investigated and compared with intact plant part and whole plant extracts. Results from the in vitro antiplasmodial testing indicated that the EtOH extract of a 1-month-old callus culture (IC(50) = 16.3 +/- 2.5 microg/ml) exhibited a higher activity than the ethanolic extracts of the fresh apical stem (IC(50) = 18.2 +/- 2.4 microg/ml) and callus cultures of 2-, 4- and 6-months-old (25 microg/ml < IC(50) < 40 microg/ml). These activities were however lower than that displayed by the ethanolic extract of the whole plant (IC(50) < 3 microg/ml). The EtOH extract of 1-month-old callus culture (the most active) was fractionated with solvents of different polarities. Its CH(2)Cl(2) fraction rich in terpenic constituents (IC(50) = 9.2 +/- 3.4 microg/ml) exhibited a higher antiplasmodial activity than its isoamylic alcohol fraction obtained at pH 2-3 (IC(50) = 25.6 +/- 2.3 microg/ml) rich in flavonoids. The activity of these two fractions was lower than that displayed by the same fractions from the whole plant (2 microg/ml < IC(50) < 3 microg/ml). Alkaloidic fractions from the whole plant and 1-month-old callus culture of fresh apical stem were considered as inactive (IC(50) > 100 microg/ml). PMID:15507366

  8. In vitro inhibitory effects of Moringa oleifera leaf extract and its major components on chemiluminescence and chemotactic activity of phagocytes.

    PubMed

    Vongsak, Boonyadist; Gritsanapan, Wandee; Wongkrajang, Yuvadee; Jantan, Ibrahim

    2013-11-01

    The ethanol extract of Moringa oleifera Lam. leaves and its major constituents, crypto-chlorogenic acid, quercetin 3-O-glucoside and kaempferol 3-O-glucoside, were investigated on the respiratory burst of human whole blood and isolated human polymorphonuclear leukocytes (PMNs) using a luminol-based chemiluminescence assay. The chemotactic migration of PMNs was also investigated using the Boyden chamber technique. The ethanol extract demonstrated inhibitory activities on the oxidative burst and the chemotactic migration of PMNs. Quercetin 3-O-glucoside, crypto-chlorogenic acid, and kaempferol 3-O-glucoside, isolated from the extract, expressed relatively strong inhibitory activity on the oxidative burst of PMNs with IC50 values of 4.1, 6.7 and 7.0 microM, respectively, comparable with that of aspirin. They also demonstrated strong inhibition of chemotatic migration of PMNs with IC50 values of 9.5, 15.9 and 18.2 microM, respectively. The results suggest that M. oleifera leaves could modulate the immune response of human phagocytes, linking to its ethnopharmacological use as an anti-inflammatory agent. The immunomodulating activity of the plant was mainly due to its major components. PMID:24427941

  9. Angiotensin-converting enzyme inhibitory activity and antioxidant properties of Nepeta crassifolia Boiss & Buhse and Nepeta binaludensis Jamzad.

    PubMed

    Tundis, Rosa; Nadjafi, Farsad; Menichini, Francesco

    2013-04-01

    This article reports phytochemical and biological studies on Nepeta binaludensis and Nepeta crassifolia. Both species were investigated for their angiotensin-converting enzyme (ACE) inhibitory activity and antioxidant properties through three in vitro models [2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and ferric reducing antioxidant power (FRAP) assay]. Aerial parts were extracted with methanol and partitioned between water and subsequently n-hexane, ethyl acetate and n-butanol. N. binaludensis methanol extract exerted significantly higher reducing power (1.9 μM Fe(II)/g) than did the positive control butylhydroxytoluene (63.2 μM Fe(II)/g) in FRAP assay. The highest DPPH radical scavenging activity was found for N. crassifolia, with IC50 values of 9.6 and 12.1 µg/mL for ethyl acetate and n-butanol fractions, respectively. n-Butanol fraction of both species showed the highest ACE inhibitory activity, with IC50 values of 59.3 and 81.7 µg/mL for N. binaludensis and N. crassifolia, respectively. Phytochemical investigations resulted in the isolation of ursolic acid, oleanolic acid, apigenin, luteolin and ixoroside. Apigenin-7-O-glucoside, 8-hydroxycirsimaritin and cirsimaritin were furthermore identified in N. crassifolia ethyl acetate-soluble fraction. Nepetanudoside B was isolated from the n-butanol fraction of N. binaludensis. PMID:22693035

  10. Extracts and constituents of Rubus chingii with 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity.

    PubMed

    Ding, Hsiou-Yu

    2011-01-01

    The 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity of the fruits of Rubus chingii was studied in vitro. Ethanolic extract, ethyl acetate and n-butanol fractions from dried R. chingii fruits revealed strong DPPH free radical scavenging activity with IC(50) values of 17.9, 3.4 and 4.0 μg/mL, respectively. The ethyl acetate and n-butanol fractions were further purified by a combination of silica gel chromatography, Lobar RP-8 chromatography, and high-pressure liquid chromatography (HPLC). Nine compounds were isolated, where methyl (3-hydroxy-2-oxo-2,3-dihydroindol-3-yl)-acetate (2), vanillic acid (5), kaempferol (7), and tiliroside (9) showed stronger DPPH free radical scavenging activity than that of ascorbic acid (131.8 μM) with IC(50) values of 45.2, 34.9, 78.5, and 13.7 μM, respectively. In addition, rubusine (1) is a new compound discovered in the present study and methyl (3-hydroxy-2-oxo-2,3-dihydroindol-3-yl)-acetate (2), methyl dioxindole-3-acetate (3), and 2-oxo-1,2-dihydroquinoline-4-carboxylic acid (4) were isolated from the fruits for the first time. PMID:21747716

  11. Antileishmanial activity of new thiophene-indole hybrids: Design, synthesis, biological and cytotoxic evaluation, and chemometric studies.

    PubMed

    Félix, Mayara B; de Souza, Edson R; de Lima, Maria do C A; Frade, Daiana Karla G; Serafim, Vanessa de L; Rodrigues, Klinger Antonio da F; Néris, Patrícia Lima do N; Ribeiro, Frederico F; Scotti, Luciana; Scotti, Marcus T; de Aquino, Thiago M; Mendonça Junior, Francisco Jaime B; de Oliveira, Márcia R

    2016-09-15

    In the present work, thirty-two hybrid compounds containing cycloalka[b]thiophene and indole moieties (TN5, TN5 1-7, TN6, TN6 1-7, TN7, TN7 1-7, TN8, TN8 1-7) were designed, synthesized and evaluated for their cytotoxic and antileishmanial activity against Leishmania amazonensis promastigotes. More than half of the compounds (18 compounds) exhibited significant antileishmanial activity (IC50 lower than 10.0μg/L), showing better performance than the reference drugs (tri- and penta-valent antimonials). The most active compounds were TN8-7, TN6-1 and TN7 with respective IC50 values of 2.1, 2.3 and 3.2μg/mL. Demonstrating that all of the compounds were less toxic than the reference drugs, even at the highest evaluated concentration (400μg/mL), no compound tested presented human erythrocyte cytotoxicity. Compound TN8-7's effectiveness against a trivalent antimony-resistant culture was demonstrated. It was observed that TN8-7's antileishmanial activity is associated with DNA fragmentation of L. amazonensis promastigotes. Chemometric studies (CPCA, PCA, and PLS) highlight intrinsic solubility/lipophilicity, and compound size and shape as closely related to activity. Our results suggest that hybrid cycloalka[b]thiophene-indole derivatives may be considered as lead compounds for further development of new drugs for the treatment of leishmaniasis. PMID:27515718

  12. Metal-based biologically active compounds: synthesis, characterization, DNA interaction, antibacterial, cytotoxic and SOD mimic activities.

    PubMed

    Patel, Mohan N; Patel, Chintan R; Joshi, Hardik N

    2013-02-01

    The square pyramidal copper(II) complexes of N, O- donor ligand and ciprofloxacin have been synthesized. Synthesized complexes were characterized by physicochemical parameters like elemental analysis, electronic, FT-IR and LC-MS spectra. The complexes were screened for their antimicrobial activity against Gram(+Ve), i.e. Staphylococcus aureus, Bacillus subtilis, and Gram(-Ve), i.e. Serratia marcescens, Pseudomonas aeruginosa and Escherichia coli, microorganisms in terms of minimum inhibitory concentration and colony-forming unit. To determine the binding mode of complexes with Herring Sperm DNA, absorption titration and viscosity measurement were employed. DNA cleavage activity was carried out by gel electrophoresis experiment using supercoiled form of pUC19 DNA. The complexes were tested for their superoxide dismutase mimic activity in terms of IC(50) value. Synthesized complexes were also screened for their cytotoxicity using brine shrimp lethality assay method. PMID:23306896

  13. Antibacterial and Cytotoxic Activity of Compounds Isolated from Flourensia oolepis.

    PubMed

    Joray, Mariana Belén; Trucco, Lucas Daniel; González, María Laura; Napal, Georgina Natalia Díaz; Palacios, Sara María; Bocco, José Luis; Carpinella, María Cecilia

    2015-01-01

    The antibacterial and cytotoxic effects of metabolites isolated from an antibacterial extract of Flourensia oolepis were evaluated. Bioguided fractionation led to five flavonoids, identified as 2',4'-dihydroxychalcone (1), isoliquiritigenin (2), pinocembrin (3), 7-hydroxyflavanone (4), and 7,4'-dihydroxy-3'-methoxyflavanone (5). Compound 1 showed the highest antibacterial effect, with minimum inhibitory concentration (MIC) values ranging from 31 to 62 and 62 to 250 μg/mL, against Gram-positive and Gram-negative bacteria, respectively. On further assays, the cytotoxic effect of compounds 1-5 was determined by MTT assay on acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) cell lines including their multidrug resistant (MDR) phenotypes. Compound 1 induced a remarkable cytotoxic activity toward ALL cells (IC50 = 6.6-9.9 μM) and a lower effect against CML cells (IC50 = 27.5-30.0 μM). Flow cytometry was used to analyze cell cycle distribution and cell death by PI-labeled cells and by Annexin V/PI staining, respectively. Upon treatment, 1 induced cell cycle arrest in the G2/M phase accompanied by a strong induction of apoptosis. These results describe for the first time the antibacterial metabolites of F. oolepis extract, with 1 being the most effective. This chalcone also emerges as a selective cytotoxic agent against sensitive and resistant leukemic cells, highlighting its potential as a lead compound. PMID:26819623

  14. Phlorotannins from Alaskan Seaweed Inhibit Carbolytic Enzyme Activity

    PubMed Central

    Kellogg, Joshua; Grace, Mary H.; Lila, Mary Ann

    2014-01-01

    Global incidence of type 2 diabetes has escalated over the past few decades, necessitating a continued search for natural sources of enzyme inhibitors to offset postprandial hyperglycemia. The objective of this study was to evaluate coastal Alaskan seaweed inhibition of α-glucosidase and α-amylase, two carbolytic enzymes involved in serum glucose regulation. Of the six species initially screened, the brown seaweeds Fucus distichus and Alaria marginata possessed the strongest inhibitory effects. F. distichus fractions were potent mixed-mode inhibitors of α-glucosidase and α-amylase, with IC50 values of 0.89 and 13.9 μg/mL, respectively; significantly more efficacious than the pharmaceutical acarbose (IC50 of 112.0 and 137.8 μg/mL, respectively). The activity of F. distichus fractions was associated with phlorotannin oligomers. Normal-phase liquid chromatography-mass spectrometry (NPLC-MS) was employed to characterize individual oligomers. Accurate masses and fragmentation patterns confirmed the presence of fucophloroethol structures with degrees of polymerization from 3 to 18 monomer units. These findings suggest that coastal Alaskan seaweeds are sources of α-glucosidase and α-amylase inhibitory phlorotannins, and thus have potential to limit the release of sugar from carbohydrates and thus alleviate postprandial hyperglycemia. PMID:25341030

  15. Benzoic acid derivatives from Piper species and their antiparasitic activity.

    PubMed

    Flores, Ninoska; Jiménez, Ignacio A; Giménez, Alberto; Ruiz, Grace; Gutiérrez, David; Bourdy, Genevieve; Bazzocchi, Isabel L

    2008-09-01

    Piper glabratum and P. acutifolium were analyzed for their content of main secondary constituents, affording nine new benzoic acid derivatives (1, 2, 4, 5, 7, and 10-13), in addition to four known compounds (3, 6, 8, and 9). Their structures were elucidated on the basis of spectroscopic data. Riguera ester reactions and optical rotation measurements established the new compounds as racemates. In the search for antiparasitic agents, the compounds were evaluated in vitro against the promastigote forms of Leishmania spp., Trypanosoma cruzi, and Plasmodium falciparum. Among the evaluated compounds, methyl 3,4-dihydroxy-5-(3'-methyl-2'-butenyl)benzoate (7) exhibited leishmanicidal effect (IC50 13.8-18.5 microg/mL) against the three Leishmania strains used, and methyl 3,4-dihydroxy-5-(2-hydroxy-3-methylbutenyl)benzoate (1), methyl 4-hydroxy-3-(2-hydroxy-3-methyl-3-butenyl)benzoate (3), and methyl 3,4-dihydroxy-5-(3-methyl-2-butenyl) benzoate (7) showed significant trypanocidal activity, with IC50 values of 16.4, 15.6, and 18.5 microg/mL, respectively. PMID:18712933

  16. Antibacterial and Cytotoxic Activity of Compounds Isolated from Flourensia oolepis

    PubMed Central

    Joray, Mariana Belén; Trucco, Lucas Daniel; González, María Laura; Napal, Georgina Natalia Díaz; Palacios, Sara María; Bocco, José Luis; Carpinella, María Cecilia

    2015-01-01

    The antibacterial and cytotoxic effects of metabolites isolated from an antibacterial extract of Flourensia oolepis were evaluated. Bioguided fractionation led to five flavonoids, identified as 2′,4′-dihydroxychalcone (1), isoliquiritigenin (2), pinocembrin (3), 7-hydroxyflavanone (4), and 7,4′-dihydroxy-3′-methoxyflavanone (5). Compound 1 showed the highest antibacterial effect, with minimum inhibitory concentration (MIC) values ranging from 31 to 62 and 62 to 250 μg/mL, against Gram-positive and Gram-negative bacteria, respectively. On further assays, the cytotoxic effect of compounds 1–5 was determined by MTT assay on acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia (CML) cell lines including their multidrug resistant (MDR) phenotypes. Compound 1 induced a remarkable cytotoxic activity toward ALL cells (IC50 = 6.6–9.9 μM) and a lower effect against CML cells (IC50 = 27.5–30.0 μM). Flow cytometry was used to analyze cell cycle distribution and cell death by PI-labeled cells and by Annexin V/PI staining, respectively. Upon treatment, 1 induced cell cycle arrest in the G2/M phase accompanied by a strong induction of apoptosis. These results describe for the first time the antibacterial metabolites of F. oolepis extract, with 1 being the most effective. This chalcone also emerges as a selective cytotoxic agent against sensitive and resistant leukemic cells, highlighting its potential as a lead compound. PMID:26819623

  17. Synthesis and antifungal activities of novel polyheterocyclic spirooxindole derivatives.

    PubMed

    Wu, Jia-Shou; Zhang, Xue; Zhang, Ying-Lao; Xie, Jian-Wu

    2015-05-01

    A series of spirooxindole tetrahydrofuran derivatives 3 were obtained in moderate to good yields via oxindole derivatives 1 and β-arylacrylonitrile derivatives 2via base-mediated cascade [3 + 2] double Michael reactions under mild conditions and the application of this method in the synthesis of bioactive analogues, such as functionalized spirooxindole octahydrofuro[3,4-c]pyridine derivatives 4 which contain two new heterocyclic rings and two quaternary carbon centers, has also been developed. Subsequently, antifungal activities of all of the synthesized compounds were evaluated against five phytopathogenic fungi (Rhizoctonia solani, Fusarium semitectum, Alternaria solani, Valsa mali and Fusarium graminearum) using the mycelium growth rate method. The preliminary results showed that the spirooxindole octahydrofuro[3,4-c]pyridine derivative 4 showed higher growth inhibition of Valsa mali and Fusarium graminearum, than spirooxindole tetrahydrofuran derivatives 3. For example, spirooxindole octahydrofuro[3,4-c]pyridine derivative 4ab, having a bromine atom at the meta position of the benzene ring, was the best compound in inhibiting F. g. with an IC50 value of 3.31, in particular with inhibition of 4ab on F. g. being similar to that of the control cycloheximide (IC50 = 3.3 μg mL(-1)). PMID:25820179

  18. In Vitro Pharmacological Activities and GC-MS Analysis of Different Solvent Extracts of Lantana camara Leaves Collected from Tropical Region of Malaysia

    PubMed Central

    Swamy, Mallappa Kumara; Akhtar, Mohd. Sayeed

    2015-01-01

    We investigated the effect of different solvents (ethyl acetate, methanol, acetone, and chloroform) on the extraction of phytoconstituents from Lantana camara leaves and their antioxidant and antibacterial activities. Further, GC-MS analysis was carried out to identify the bioactive chemical constituents occurring in the active extract. The results revealed the presence of various phytocompounds in the extracts. The methanol solvent recovered higher extractable compounds (14.4% of yield) and contained the highest phenolic (92.8 mg GAE/g) and flavonoid (26.5 mg RE/g) content. DPPH radical scavenging assay showed the IC50 value of 165, 200, 245, and 440 μg/mL for methanol, ethyl acetate, acetone, and chloroform extracts, respectively. The hydroxyl scavenging activity test showed the IC50 value of 110, 240, 300, and 510 μg/mL for methanol, ethyl acetate, acetone, and chloroform extracts, respectively. Gram negative bacterial pathogens (E. coli and K. pneumoniae) were more susceptible to all extracts compared to Gram positive bacteria (M. luteus, B. subtilis, and S. aureus). Methanol extract had the highest inhibition activity against all the tested microbes. Moreover, methanolic extract of L. camara contained 32 bioactive components as revealed by GC-MS study. The identified major compounds included hexadecanoic acid (5.197%), phytol (4.528%), caryophyllene oxide (4.605%), and 9,12,15-octadecatrienoic acid, methyl ester, (Z,Z,Z)- (3.751%). PMID:26783409

  19. Antiplasmodial, cytotoxic activities and characterization of a new naturally occurring quinone methide pentacyclic triterpenoid derivative isolated from Salacia leptoclada Tul. (Celastraceae) originated from Madagascar

    PubMed Central

    Ruphin, Fatiany Pierre; Baholy, Robijaona; Emmanue, Andrianarivo; Amelie, Raharisololalao; Martin, Marie-Therese; Koto-te-Nyiwa, Ngbolua

    2013-01-01

    Objective To validate scientifically the traditional use of Salacia leptoclada Tul. (Celastraceae) (S. leptoclada) and to isolate and elucidate the structure of the biologically active compound. Methods Bioassay-guided fractionation of the acetonic extract of the stem barks of S. leptoclada was carried out by a combination of chromatography technique and biological experiments in viro using Plasmodium falciparum and P388 leukemia cell lines as models. The structure of the biologically active pure compound was elucidated by 1D and 2D NMR spectroscopy and mass spectrometry. Results Biological screening of S. leptoclada extracts resulted in the isolation of a pentacyclic triterpenic quinone methide. The pure compound exhibited both in vitro a cytotoxic effect on murine P388 leukemia cells with IC50 value of (0.041±0.020) µg/mL and an antiplasmodial activity against the chloroquine-resistant strain FC29 of Plasmodium falciparum with an IC50 value of (0.052±0.030) µg/mL. Despite this interesting anti-malarial property of the lead compound, the therapeutic index was weak (0.788). In the best of our knowledge, the quinone methide pentacyclic triterpenoid derivative compound is reported for the first time in S. leptoclada. Conclusions The results suggest that furthers studies involving antineoplastic activity is needed for the development of this lead compound as anticancer drug. PMID:24075342

  20. In vitro potential modulation of baicalin and baicalein on P-glycoprotein activity and expression in Caco-2 cells and rat gut sacs.

    PubMed

    Miao, Qing; Wang, Zhiyong; Zhang, Yuanyuan; Miao, Peipei; Zhao, Yuanyuan; Zhang, Yujie; Ma, Shuangcheng

    2016-09-01

    Context Previous studies have shown that Scutellariae Radix, the dried root of Scutellaria baicalensis Georgi (Labiatae), has a certain inhibitory effect on P-glycoprotein (P-gp), but the effects of its main active constituents on P-gp are still ambiguous. Objectives In vitro studies were performed to investigate the effects of its main active constituents (baicalin and its aglycone, baicalein) on the activity and expression of P-gp in intestine using Caco-2 cells and rat gut sacs. Materials and methods In Caco-2 cell experiments, the effects of baicalin and baicalein on P-gp activity were investigated using a P-gp substrate, rhodamine 123 and non-substrate fluorescein Na, by determining their intracellular fluorescence accumulation, and their effects on P-gp expression were determined using flow cytometry. In addition, rat gut sac model was selected to investigate the effects of baicalin and baicalein on the transport of verapamil, a classical P-gp substrate. The gut sacs of male Sprague-Dawley rats were filled with 0.4 mL the test solution contained verapamil (0.2575 mg/mL) and the drugs [baicalin and baicalein, at concentrations of 1/8 IC50 (59.875, 41.5 μg/mL), 1/4 IC50 (119.75, 83 μg/mL) and 1/2 IC50 (239.5, 166 μg/mL)], and then incubated in Tyrode's solution for a period of time. After termination of the incubation, the incubated solution was processed for the subsequent detection. Results According to the results of MTT assay, the IC50 values of verapamil, baicalin and baicalein were 104, 479, 332 μg/mL, respectively. The obtained results from the two models were confirmed mutually. As a result, baicalin exhibited no obvious effect on intracellular accumulation of Rh-123, and almost had no effect on P-gp expression and verapamil transportation, while baicalein significantly increased intracellular accumulation of Rh-123 (p < 0.01), down-regulated P-gp expression (p < 0.01) and increased the transport of verapamil (p < 0

  1. Mutagenic, antimutagenic, antioxidant, anti-lipoxygenase and antimicrobial activities of Scandix pecten-veneris L.

    PubMed

    Sharifi-Rad, M; Tayeboon, G S; Miri, A; Sharifi-Rad, M; Setzer, W N; Fallah, F; Kuhestani, K; Tahanzadeh, N; Sharifi-Rad, J

    2016-01-01

    Scandix pecten-veneris L. or Shepherd's-needle is a weed species used in some countries for medicinal purposes. In this study S. pecten-veneris leaves were shade dried, powdered and extracted with methanol. The purpose of this study was to assay the in vitro mutagenic, antimutagenic, antioxidant, antilipoxygenase and antimicrobial activities of S. pecten-veneris leaf extract. The methanolic extract indicated no mutagenicity when tested with Salmonella typhimurium strains TA98 and TA100. Antimutagenic activity was reported with inhibition of mutagenicity in a concentration dependent fashion. The methanolic extract demonstrated antioxidant activity in the DPPH radical-scavenging test (IC50 = 4.57 mg/mL), comparable to ascorbic acid and BHT. Moreover, the extract presented a remarkable and potent inhibition against soybean lipoxygenase (IC50 = 641.57 µg/mL). The methanolic extract was examined for its antimicrobial powers against four different bacteria with MIC values >100. Our results introduced this plant as a useful factor for the treatment of cancer, inflammatory and infectious diseases. PMID:27262795

  2. New urushiols with platelet aggregation inhibitory activities from resin of Toxicodendron vernicifluum.

    PubMed

    Xie, Ya; Zhang, Jie; Liu, Wenyuan; Xie, Ning; Feng, Feng; Qu, Wei

    2016-07-01

    Eight new urushiol-type compounds (1-7b), along with seven known compounds were isolated from the resin of Toxicodendron vernicifluum Stokes. Their structures were determined by extensive spectroscopic methods, included (1)H NMR, (13)C NMR, HMQC, HMBC, HRESIMS, EI-MS in combination with CD methods. All the compounds except 7a and 7b were evaluated for their anti-platelet aggregation activities in vitro. Among them, compound 5 (IC50=5.12±0.85μmol/L), with a vic-diol moiety in the long alkyl chain showed the most potent inhibitory of platelet aggregation activity induced by ADP. In addition, compound 6 showed the effect of anti-platelet aggregation induced by AA with the IC50 value of 3.09±0.70μmol/L. Thus, these compounds might be the active components to the traditional use of Resina Toxicodendri for breaking up blood stasis, which could be related to the anti-platelet aggregation. PMID:27156871

  3. Active Inference, Epistemic Value, and Vicarious Trial and Error

    ERIC Educational Resources Information Center

    Pezzulo, Giovanni; Cartoni, Emilio; Rigoli, Francesco; io-Lopez, Léo; Friston, Karl

    2016-01-01

    Balancing habitual and deliberate forms of choice entails a comparison of their respective merits--the former being faster but inflexible, and the latter slower but more versatile. Here, we show that arbitration between these two forms of control can be derived from first principles within an Active Inference scheme. We illustrate our arguments…

  4. The Role of Values in Promoting Physical Activity

    ERIC Educational Resources Information Center

    Kosma, Maria; Buchanan, David R.; Hondzinski, Jan

    2015-01-01

    Despite the proliferation of theory-based behavior-change programs to promote physical activity, obesity and diabetes rates continue to rise. Given the notable ineffective interventions, it is important to examine why these efforts have been largely unsuccessful and to consider potential alternatives. The purpose of this article is to consider the…

  5. Biological activities and chemical composition of lichens from Serbia

    PubMed Central

    Kosanic, Marijana; Rankovic, Branislav; Stanojkovic, Tatjana; Vasiljevic, Perica; Manojlovic, Nedeljko

    2014-01-01

    The aim of this study is to investigate chemical composition of acetone extracts of the lichens Parmelia arseneana and Acarospora fuscata and in vitro antioxidant, antimicrobial, and anticancer activities of these extracts and gyrophoric acid isolated from A. fuscata. The HPLC-UV method was used for the identification of secondary metabolites. Stictic acid, norstictic acid, gyrophoric acid, usnic acid, atranorin and chloroatranorin were identified in the A. fuscata. In P. arseneana, we detected stictic acid, norstictic acid, usnic acid and atranorin, while gyrophoric acid was not identified. Antioxidant activity was evaluated by measuring the scavenging capacity of tested samples on DPPH and superoxide anion radicals, reducing the power of samples and determination of total phenolic compounds in extracts. As a result of the study, gyrophoric acid was found to have the largest DPPH radical scavenging activity with an IC50 value of 105.75 µg/ml. Moreover, the tested samples had an effective superoxide anion radical scavenging and reducing power. The total content of phenol in extracts was determined as pyrocatechol equivalent. The antimicrobial activity was estimated by determination of the minimal inhibitory concentration by the broth microdilution method. The most active was also gyrophoric acid, with minimum inhibitory concentration values ranging from 0.019 to 1.25 mg/ml. Anticancer activity was tested against LS174 (human colon carcinoma cell line), A549 (human lung carcinoma cell line), Fem-x (malignant melanoma cell line), and a chronic myelogeneous leukaemia K562 cell line using the MTT method. Extract of P. arseneana expressed the strongest anticancer activity against all cell lines with IC50 values ranging from 11.61 to 47.06 µg/ml. PMID:26417336

  6. Influence of organophosphorus pesticides on peroxidase and chlorination activity of human myeloperoxidase.

    PubMed

    Lazarević-Pašti, Tamara; Momić, Tatjana; Radojević, Miloš M; Vasić, Vesna

    2013-09-01

    Inhibitory effects of five organophosphorus pesticides (diazinon, malathion, chlorpyrifos, azinphos-methyl and phorate) and their oxo-analogs on human myeloperoxidase (MPO) activity were investigated. While inspecting separately peroxidase and chlorination activity, it was observed that investigated OPs affect peroxidase activity, but not chlorination activity. Among investigated pesticides, malathion and malaoxon have showed the highest power to inhibit MPO peroxidase activity with IC50 values of the order of 3×10(-7) and 5×10(-9) M, respectively. It was proposed that inhibition trend is rendered by molecular structure which invokes steric hindrance for OPs interaction with MPO active center responsible for peroxidase activity. In addition, it was concluded that physiological function of MPO is not affected by any of the investigated OPs. PMID:25149236

  7. Biological activities of water-soluble fullerene derivatives

    NASA Astrophysics Data System (ADS)

    Nakamura, S.; Mashino, T.

    2009-04-01

    Three types of water-soluble fullerene derivatives were synthesized and their biological activities were investigated. C60-dimalonic acid, an anionic fullerene derivative, showed antioxidant activity such as quenching of superoxide and relief from growth inhibition of E. coli by paraquat. C60-bis(7V,7V-dimethylpyrrolidinium iodide), a cationic fullerene derivative, has antibacterial activity and antiproliferative effect on cancer cell lines. The mechanism is suggested to be respiratory chain inhibition by reactive oxygen species produced by the cationic fullerene derivative. Proline-type fullerene derivatives showed strong inhibition activities on HIV-reverse transcriptase. The IC50 values were remarkably lower than nevirapine, a clinically used anti-HIV drug. Fullerene derivatives have a big potential for a new type of lead compound to be used as medicine.

  8. Decoding the representation of numerical values from brain activation patterns.

    PubMed

    Damarla, Saudamini Roy; Just, Marcel Adam

    2013-10-01

    Human neuroimaging studies have increasingly converged on the possibility that the neural representation of specific numbers may be decodable from brain activity, particularly in parietal cortex. Multivariate machine learning techniques have recently demonstrated that the neural representation of individual concrete nouns can be decoded from fMRI patterns, and that some patterns are general over people. Here we use these techniques to investigate whether the neural codes for quantities of objects can be accurately decoded. The pictorial mode (nonsymbolic) depicted a set of objects pictorially (e.g., a picture of three tomatoes), whereas the digit-object mode depicted quantities as combination of a digit (e.g., 3) with a picture of a single object. The study demonstrated that quantities of objects were decodable from neural activation patterns, in parietal regions. These brain activation patterns corresponding to a given quantity were common across objects and across participants in the pictorial mode. Other important findings included better identification of individual numbers in the pictorial mode, partial commonality of neural patterns across the two modes, and hemispheric asymmetry with pictorially-depicted numbers represented bilaterally and numbers in the digit-object mode represented primarily in the left parietal regions. The findings demonstrate the ability to identify individual quantities of objects based on neural patterns, indicating the presence of stable neural representations of numbers. Additionally, they indicate a predominance of neural representation of pictorially depicted numbers over the digit-object mode. PMID:22505340

  9. Inhibitors of Urokinase Type Plasminogen Activator and Cytostatic Activity from Crude Plants Extracts

    PubMed Central

    Zha, Xueqiang; Diaz, Ricardo; Franco, Jose Javier Rosado; Sanchez, Veronica Forbes; Fasoli, Ezio; Barletta, Gabriel; Carvajal, Augusto; Bansal, Vibha

    2014-01-01

    In view of the clear evidence that urokinase type plasminogen activator (uPA) plays an important role in the processes of tumor cell metastasis, aortic aneurysm, and multiple sclerosis, it has become a target of choice for pharmacological intervention. The goal of this study was thus to determine the presence of inhibitors of uPA in plants known traditionally for their anti-tumor properties. Crude methanol extracts were prepared from the leaves of plants (14) collected from the subtropical dry forest (Guanica, Puerto Rico), and tested for the presence of inhibitors of uPA using the fibrin plate assay. The extracts that tested positive (6) were then partitioned with petroleum ether, chloroform, ethyl acetate and n-butanol, in a sequential manner. The resulting fractions were then tested again using the fibrin plate assay. Extracts from leaves of Croton lucidus (C. lucidus) showed the presence of a strong uPA inhibitory activity. Serial dilutions of these C. lucidus partitions were performed to determine the uPA inhibition IC50 values. The chloroform extract showed the lowest IC50 value (3.52 μg/mL) and hence contained the most potent uPA inhibitor. Further investigations revealed that the crude methanol extract and its chloroform and n-butanol partitions did not significantly inhibit closely related proteases such as the tissue type plasminogen activator (tPA) and plasmin, indicating their selectivity for uPA, and hence superior potential for medicinal use with fewer side effects. In a further evaluation of their therapeutic potential for prevention of cancer metastasis, the C. lucidus extracts displayed cytostatic activity against human pancreatic carcinoma (PaCa-2) cells, as determined through an MTS assay. The cytostatic activities recorded for each of the partitions correlated with their relative uPA inhibitory activities. There are no existing reports of uPA inhibitors being present in any of the plants reported in this study. PMID:23896619

  10. In vitro study of the PLA2 inhibition and antioxidant activities of Aloe vera leaf skin extracts

    PubMed Central

    2011-01-01

    Background In the present work we determined the total phenolic content of Aloe vera leaf skin (AVLS) extracts by using various solvents (hexane, chloroform-ethanol (1/1), ethyl acetate, butanol and water). We have also evaluated the antioxidant and the anti-PLA2 properties of these extracts by measuring their inhibition potency on the human pro-inflammatory phospholipase A2 (group IIA). Results The water extract exhibits the highest inhibitory effect with an IC50 = 0.22 mg/ml and interestingly no effect was observed on the digestive phospholipase A2 (group IB) even at a concentration of 5 mg/ml. Antioxidant activities were also analyzed and the most active extracts were observed when using chloroform ethanol (1/1) and ethyl acetate (IC50 = 0.274 and 0.326 mg/ml, respectively). Analysis of the total phenolic content reveals that the water extract, with the best anti-PLA2 effect, was poor in phenolic molecules (2 mg GAE/g). This latter value has to be compared with the chloroform-ethanol and the ethyl acetate extracts (40 and 23.8 mg GAE/g, respectively), mostly responsible for the antioxidant activity. Conclusion A significant correlation was established between the total phenolic content and the antioxidant capacity but not with the anti PLA2 activity. Results from phytochemical screening suggest that the anti PLA2 molecules were probably catechin tannins compounds. PMID:21310091

  11. Biological Activities of xylooligosaccharides generated from garlic straw xylan by purified xylanase from Bacillus mojavensis UEB-FK.

    PubMed

    Kallel, Fatma; Driss, Dorra; Chaabouni, Semia Ellouz; Ghorbel, Raoudha

    2015-01-01

    A newly isolated Bacterium strain named UEB-FK was selected from Tunisian Sahara, exhibiting the highest clear zone on agar plates containing oat spelt xylan by staining with Congo red. On the basis of 16S rDNA sequence analysis, this strain was identified as Bacillus mojavensis. This strain produced extracellular xylanase. Xylanase from the strain was purified to homogeneity and had an apparent molecular weight of 14 kDa. The K m and V max values of the purified xylanase on oat spelt xylan were 3.85 mg/mL and 250.02 U/mg, respectively. The optimum pH and temperature for the enzyme were found to be 4.0 and 50 °C, respectively, and the enzyme exhibited significant heat stability. In addition, the enzyme was found to be stable in a wide range of pH (3-9). The main hydrolysis products yielded from garlic straw-extracted xylan were xylobiose and xylotriose. The antioxidant and antibacterial activities of xylan oligosaccharide (XOS) were investigated. As regards to the in vitro antioxidant activities, the XOS showed a important DPPH (1,1-diphenyl-2-picrylhydrazyl) scavenging activity (IC50 = 0.45 mg/mL) and a high β-carotene bleaching (IC50 = 2.2 mg/mL). Furthermore, XOS had a high antimicrobial activity against Klebsiella pneumoniae, Enterococcus faecalis, Bacillus thuringiensis, and Pseudomonas aeruginosa. PMID:25351626

  12. In Silico Screening, Structure-Activity Relationship, and Biologic Evaluation of Selective Pteridine Reductase Inhibitors Targeting Visceral Leishmaniasis▿ †

    PubMed Central

    Kaur, Jaspreet; Kumar, Pranav; Tyagi, Sargam; Pathak, Richa; Batra, Sanjay; Singh, Prashant; Singh, Neeloo

    2011-01-01

    In this study we utilized the concept of rational drug design to identify novel compounds with optimal selectivity, efficacy and safety, which would bind to the target enzyme pteridine reductase 1 (PTR1) in Leishmania parasites. Twelve compounds afforded from Baylis-Hillman chemistry were docked by using the QUANTUM program into the active site of Leishmania donovani PTR1 homology model. The biological activity for these compounds was estimated in green fluorescent protein-transfected L. donovani promastigotes, and the most potential analogue was further investigated in intracellular amastigotes. Structure-activity relationship based on homology model drawn on our recombinant enzyme was substantiated by recombinant enzyme inhibition assay and growth of the cell culture. Flow cytometry results indicated that 7-(4-chlorobenzyl)-3-methyl-4-(4-trifluoromethyl-phenyl)-3,4,6,7,8,9-hexahydro-pyrimido[1,2-a]pyrimidin-2-one (compound 7) was 10 times more active on L. donovani amastigotes (50% inhibitory concentration [IC50] = 3 μM) than on promastigotes (IC50 = 29 μM). Compound 7 exhibited a Ki value of 0.72 μM in a recombinant enzyme inhibition assay. We discovered that novel pyrimido[1,2-a]pyrimidin-2-one systems generated from the allyl amines afforded from the Baylis-Hillman acetates could have potential as a valuable pharmacological tool against the neglected disease visceral leishmaniasis. PMID:21115787

  13. Constituents, biological activities and quality control parameters of the crude extract and essential oil from Arracacia tolucensis var. multifida.

    PubMed

    Figueroa, Mario; Rivero-Cruz, Isabel; Rivero-Cruz, Blanca; Bye, Robert; Navarrete, Andrés; Mata, Rachel

    2007-08-15

    Bioassay guided fractionation of an antimycobacterial extract of Arracacia tolucensis var. multifida (Umbelliferae) led to the isolation of isoimperatorin (1), osthol (2), suberosin (3), 8-methoxypsoralen (8-MOP) (4), herniarin (5), scoparone (6), umbelliferone (7), dihydroxypeucedanin (8), 5-methoxypsoralen (5-MOP) (9), isoscopoletin (10) and scopoletin (11). The isolates were tested against Mycobacterium tuberculosis and only 1-4 showed significant activity with MIC values of 64, 32, 16 and 128 microg/mL, respectively. The essential oil showed moderate in vitro antibacterial activity against representative Gram-positive and Gram-negative bacteria. The volatile oil of Arracacia tolucensis var. multifida was analyzed by GC-MS and found to be composed mainly by 2 and 3. The essential oil (IC(50)=116.4+/-23.2 microg/mL) and the extract (IC(50)=1153.1+/-53.2 microg/mL) of the plant provoked concentration dependent inhibition of the tone and amplitude of the guinea-pig ileum spontaneous contractions; the latter activity was related with the high coumarin content of this species. A suitable (novel and rapid) HPLC method to quantify the major active coumarins of the plant was developed. The method provides also a reproducible fingerprint useful for identity tests of this plant. PMID:17582715

  14. Isolation and identification of 5-hydroxyl-5-methyl-2-hexenoic acid from Actinoplanes sp. HBDN08 with antifungal activity.

    PubMed

    Zhang, Ji; Wang, Xiang-Jing; Yan, Yi-Jun; Jiang, Ling; Wang, Ji-Dong; Li, Bao-Ju; Xiang, Wen-Sheng

    2010-11-01

    A bioactivity-guided approach was employed to isolate and determine the chemical identity of bioactive constituents with antifungal activity from Actinoplanes sp. HBDN08. The structure of the antifungal metabolite was elucidated as 5-hydroxyl-5-methyl-2-hexenoic acid on the basis of spectral analysis. This compound showed strong in vitro antifungal activity against Botrytis cinerea, Cladosporium cucumerinum and Corynespora cassiicola, with an IC(50) of 32.45, 27.17, and 30.66 mg/L, respectively; however, it only moderately inhibited hyphal growth of Rhizoctonia solani with an IC(50) of 61.64 mg/L. The in vivo antifungal activity under greenhouse conditions demonstrated that 5-hydroxyl-5-methyl-2-hexenoic acid could effectively control the diseases caused by B. cinerea, C. cucumerinum and C. cassiicola with 71.42%, 78.63% and 65.13% control values at 350 mg/L, respectively. This strong antifungal activity suggests that 5-hydroxyl-5-methyl-2-hexenoic acid might be a promising candidate for new antifungal agents. PMID:20584599

  15. Design, synthesis and structure-activity relationships of novel 4-phenoxyquinoline derivatives containing pyridazinone moiety as potential antitumor agents.

    PubMed

    Zhou, Shunguang; Liao, Huimin; He, Chao; Dou, Yanan; Jiang, Mingyan; Ren, Lixiang; Zhao, Yanfang; Gong, Ping

    2014-08-18

    A series of novel 4-phenoxyquinoline derivatives containing pyridazinone moiety were synthesized and evaluated for their in vitro cytotoxic activity against five cancer cell lines (HT-29, H460, A549, MKN-45, and U87MG). Most of the compounds exhibited moderate-to-significant cytotoxicity and high selectivity against one or more cell lines. Compounds 15a, 20a, 15b, 15c, 20d, and 16e were further examined for their inhibitory activity against c-Met kinase. The most promising compound 15a (c-Met half-maximal inhibitory concentration [IC50] = 2.15 nM) showed remarkable cytotoxicity against HT-29, H460, and A549 cell lines with IC50 values of 0.10 μM, 0.13 μM, and 0.05 μM, respectively, and thus it was 1.5- to 2.3-fold more potent than foretinib. Their preliminary structure-activity relationships (SARs) studies indicate that electron-withdrawing groups on the terminal phenyl rings are beneficial for improving the antitumor activity. PMID:24996144

  16. Effect of Okinawa Propolis on PAK1 Activity, Caenorhabditis elegans Longevity, Melanogenesis, and Growth of Cancer Cells.

    PubMed

    Taira, Nozomi; Nguyen, Binh Cao Quan; Be Tu, Pham Thi; Tawata, Shinkichi

    2016-07-13

    Propolis from different areas has been reported to inhibit oncogenic/aging kinase PAK1, which is responsible for a variety of conditions, including cancer, longevity, and melanogenesis. Here, a crude extract of Okinawa propolis (OP) was tested against PAK1 activity, Caenorhabditis elegans (C. elegans) longevity, melanogenesis, and growth of cancer cells. We found that OP blocks PAK1 and exhibits anticancer activity in the A549 cell (human lung cancer cell) line with IC50 values of 6 μg/mL and 12 μg/mL, respectively. Most interestingly, OP (1 μg/mL) significantly reduces reproduction and prolongs the lifespan of C. elegans by activating the HSP-16.2 gene, as shown in the PAK1-deficient strain. Furthermore, OP inhibits melanogenesis in a melanoma cell line (B16F10) by downregulating intracellular tyrosinase activity with an IC50 of 30 μg/mL. Our results suggest that OP demonstrated a life span extending effect, C. elegans, anticancer, and antimelanogenic effects via PAK1 inactivation; therefore, this can be a potent natural medicinal supplement against PAK1-dependent diseases. PMID:27337169

  17. Amaranth peptides from simulated gastrointestinal digestion: antioxidant activity against reactive species.

    PubMed

    Delgado, María C Orsini; Galleano, Mónica; Añón, María C; Tironi, Valeria A

    2015-03-01

    We evaluated the capacity of simulated gastrointestinal digests or alcalase hydrolysates of protein isolates from amaranth to scavenge diverse physiologically relevant reactive species. The more active hydrolysate was obtained with the former method. Moreover, a prior alcalase treatment of the isolate followed by the same simulated gastrointestinal digestion did not improve the antioxidant capacity in any of the assays performed and even produced a negative effect under some conditions. Gastrointestinal digestion produced a strong increment in the scavenging capacity against peroxyl radicals (ORAC assay), hydroxyl radicals (ESR-OH assay), and peroxynitrites; thus decreasing the IC50 values to approximately 20, 25, and 20%, respectively, of the levels attained with the nonhydrolyzed proteins. Metal chelation (HORAC assay) also enhanced respect to isolate levels, but to a lesser extent (decreasing IC50 values to only 50%). The nitric-oxide- and superoxide-scavenging capacities of the digests were not relevant with respect to the methodologies used. The gastrointestinal digests from amaranth proteins acted against reactive species by different mechanisms, thus indicating the protein isolate to be a potential polyfunctional antioxidant ingredient. PMID:25577328

  18. Evaluation of anti-oxidant activities and total phenolic content of Chromolaena odorata.

    PubMed

    Srinivasa Rao, K; Chaudhury, Pradeep Kumar; Pradhan, Anshuman

    2010-02-01

    The aim of this study was to assess the in vitro potential of chloroform extract of Chromolaena odorata leaves. The DPPH activity of the extract (0.1-5 mg/ml) was increased in a dose dependent manner, which was found in the range of 23.48-91.61% as compared to ascorbic acid (33.69-94.10%). The IC50 values of chloroform extract in DPPH radical, hydroxyl radical, nitric oxide, ABTS radical were obtained to be 0.31, 0.43, 0.28 and 1.32 mg/ml, respectively. However, the IC50 values for the standard ascorbic acid were noted to be 0.24, 0.41, 0.23 and 1 mg/ml, respectively. Measurement of total phenolic content of the chloroform extract of C. odorata was achieved using Folin-Ciocalteau reagent containing 242.2 mg/g of phenolic content, which was found significantly higher when compared to reference standard gallic acid. The results obtained in this study clearly indicate that C. odorata has a significant potential to use as a natural anti-oxidant agent. PMID:20026159

  19. Cytotoxic Activities against Breast Cancer Cells of Local Justicia gendarussa Crude Extracts

    PubMed Central

    Abd Samad, Azman; Jamil, Shajarahtunnur

    2014-01-01

    Justicia gendarussa methanolic leaf extracts from five different locations in the Southern region of Peninsular Malaysia and two flavonoids, kaempferol and naringenin, were tested for cytotoxic activity. Kaempferol and naringenin were two flavonoids detected in leaf extracts using gas chromatography-flame ionization detection (GC-FID). The results indicated that highest concentrations of kaempferol and naringenin were detected in leaves extracted from Mersing with 1591.80 mg/kg and 444.35 mg/kg, respectively. Positive correlations were observed between kaempferol and naringenin concentrations in all leaf extracts analysed with the Pearson method. The effects of kaempferol and naringenin from leaf extracts were examined on breast cancer cell lines (MDA-MB-231 and MDA-MB-468) using MTT assay. Leaf extract from Mersing showed high cytotoxicity against MDA-MB-468 and MDA-MB-231 with IC50 values of 23 μg/mL and 40 μg/mL, respectively, compared to other leaf extracts. Kaempferol possessed high cytotoxicity against MDA-MB-468 and MDA-MB-231 with IC50 values of 23 μg/mL and 34 μg/mL, respectively. These findings suggest that the presence of kaempferol in Mersing leaf extract contributed to high cytotoxicity of both MDA-MB-231 and MDA-MB-468 cancer cell lines. PMID:25574182

  20. Phytochemical Investigation of Cycas circinalis and Cycas revoluta Leaflets: Moderately Active Antibacterial Biflavonoids

    PubMed Central

    Moawad, Abeer; Hetta, Mona; Zjawiony, Jordan K.; Jacob, Melissa R.; Hifnawy, Mohamed; Ferreira, Daneel

    2013-01-01

    Chemical examination of the methanolic extract of the leaflets of Cycas circinalis L. led to the isolation of one new biflavonoid, (2S, 2″S)-2,3,2″,3″-tetrahydro-4′,4‴-di-O-methylamentoflavone (tetrahydroisoginkgetin; 2), and 15 known compounds, 11 of which are reported for the first time from C. circinalis. Chromatographic separation of the chloroform extract of C. revoluta Thunb. leaflets afforded 12 compounds, seven of which are reported for the first time from this species. The isolated compounds from both species include 14 biflavonoids, three lignans, three flavan-3-ols, two flavone-C-glucosides, two nor-isoprenoids, and one flavanone. This is the first report of NMR and CD data of 2,3,2″,3″-tetrahydro-4′-O-methyl- and 2,3-dihydro-4′-O-methyl-amentoflavone (6) and (7). The effect of O-methylation on the chemical shifts of the neighboring carbons in the 13C NMR spectra of the dihydro- and tetrahydro-amentoflavone skeletons provides a tool to identify the location of the methoxy groups. Compounds 2, 6, and 18 displayed moderate antibacterial activity against Staphylococcus aureus (IC50 values of 3.8, 9.6, and 8.2 μM, respectively) and methicillin-resistant S. aureus (MRSA; IC50 values of 5.9, 12.5, and 11.5 μM, respectively). PMID:20072955

  1. Structural Characterization and Biological Activities of Polysaccharides from Olive Mill Wastewater.

    PubMed

    Nadour, Malika; Laroche, Celine; Pierre, Guillaume; Delattre, Cedric; Moulti-Mati, Farida; Michaud, Philippe

    2015-09-01

    Olive mill wastewater (OMWW), the main waste product of olive oil extraction process, was investigated as a source of polysaccharides. The yield of alcohol insoluble residue (AIR) was 20.5 % based on the dry matter of OMWW. Extraction with water gave water soluble (WSF) and insoluble (WIF) fractions from AIR with yields of 13.3 % (w/w) and 3.7 % (w/w) based on the dry matter, respectively. Chemical composition and monosaccharide analysis indicated that glucose was the main monosaccharide of these extracts in addition to galactose, arabinose, rhamnose, and galacturonic acid. Prebiotic and antioxidant activities of polysaccharidic fractions from OMWW were evaluated. Results gave evidence for their scavenging capacity toward the 2,2'-diphenyl-1-picrylhydrazyle (DPPH) (IC50 value of 89.43 μg/mL) and hydroxyl radicals (IC50 value of 158.70 μg/mL), resistance toward artificial human gastric juice, and ability to be fermented by Lactobacilli strains. PMID:26189104

  2. Design, synthesis and cytotoxic activity of a novel series of steroidal phenylpyrazoles.

    PubMed

    Li, Jian; Zhao, Ximei; Li, Longbo; Yuan, Zhipeng; Tan, Fangfang; Shi, Baojun; Zhang, Jiwen

    2016-03-01

    Thirty novel steroidal pyrazole derivatives were designed and synthesized via a highly efficient route from pregnenolone (1) as starting material. The key intermediates 3a-c were obtained under Vilsmeier conditions, and the subsequent hydrolysis, acetylation or Borch reduction afforded thirty target compounds. These compounds were mainly characterized by (1)H NMR, (13)C NMR, DEPT135°. The structure of compound 3a was also confirmed by X-ray single crystal diffraction. The cytotoxicity of these compounds was evaluated by the SRB method against four cancer cell lines, including A549, Hela, MCF-7 and HepG2, and the results indicated that compounds 5a, 6a, 7a and 8a exhibited significant cytotoxicity with IC50 values ranging from 0.91 to 5.44 μM. Most importantly, compound 5a exhibited excellent cytotoxicity against A549 with an IC50 value of 0.91 μM. On the basis of our research the structure-activity relationships (SAR) of these compounds were discussed. This work provides some important hints for further structural modification of steroids towards developing novel and highly effective anticancer drugs. PMID:26742627

  3. American, Chinese, and Japanese Students' Acceptance of Their Parents' Values about Academic and Social Activities.

    ERIC Educational Resources Information Center

    Chen, Chuansheng

    This study investigates cross-cultural differences in students' acceptance of their parents' values about education and social activities. It also examines the relation between acceptance of values and such factors as type of values, knowledge of parental values, mathematics achievement, and psychological well-being. Participants were over 3,000…

  4. Structure-Activity Relationship Studies of Isomeric 2,4-Diaminoquinazolines on β-Amyloid Aggregation Kinetics.

    PubMed

    Mohamed, Tarek; Shakeri, Arash; Tin, Gary; Rao, Praveen P N

    2016-05-12

    A library of isomeric 2,4-diaminoquinazoline (DAQ) derivatives were synthesized and evaluated for antiaggregation potential toward Aβ40/42. Structure-activity relationship data identified compound 3k (N (4)-(4-bromobenzyl)quinazoline-2,4-diamine) with a 4-bromobenzyl substituent as the most potent inhibitor (Aβ40 IC50 = 80 nM) and was almost 18-fold more potent compared to the reference agent curcumin (Aβ40 IC50 = 1.5 μM). The corresponding N (2)-isomer 4k (N (2)-(4-bromobenzyl)quinazoline-2,4-diamine) was also able to prevent Aβ aggregation (Aβ40 IC50 = 1.7 μM). However, compound 4k exhibited superior inhibition of Aβ42 aggregation (Aβ42 IC50 = 1.7 μM) compared to compound 3k (Aβ42 IC50 = 14.8 μM) and was ∼1.8-fold more potent compared to curcumin (Aβ42 IC50 = 3.1 μM). These results were supported by Aβ aggregation kinetics investigations and transmission electron microscopy studies, which demonstrate the suitability of DAQ ring system to develop antiamyloid agents as pharmacological tools to study Aβ aggregation. PMID:27190601

  5. Erinacerins C-L, isoindolin-1-ones with α-glucosidase inhibitory activity from cultures of the medicinal mushroom Hericium erinaceus.

    PubMed

    Wang, Kai; Bao, Li; Qi, Qiuyue; Zhao, Feng; Ma, Ke; Pei, Yunfei; Liu, Hongwei

    2015-01-23

    The well-known edible and medicinal mushroom Hericium erinaceus produces various bioactive secondary metabolites. Ten new isoindolin-1-ones, named erinacerins C-L (1-10), together with (E)-5-(3,7-dimethylocta-2,6-dien-1-yl)-4-hydroxy-6-methoxy-2-phenethylisoindolin-1-one (11) were isolated from the solid culture of H. erinaceus. The structures of new metabolites were established by spectroscopic methods. The absolute configurations of 3, 4, 9, and 10 were assigned by comparing their specific rotations with those of related phthalimidines (13-20). Compounds 5 and 6, 7 and 8, and 9 and 10 are double-bond positional isomers. In a α-glucosidase inhibition assay, compounds 2-11 showed inhibitory activity with IC50 values ranging from 5.3 to 145.1 μM. Preliminary structure-activity analysis indicated that the terpenoid side chain and the phenolic hydroxy groups contributed greatly to the α-glucosidase inhibitory activity of 1-11. In a cytotoxicity assay, compound 11 also presented weak cytotoxicity against two cell lines, A549 and HeLa, with IC50 values of 49.0 and 40.5 μM. PMID:25565282

  6. Phytochemicals of Salacia oblonga responsible for free radical scavenging and antiproliferative activity against breast cancer cell lines (MDA-MB-231).

    PubMed

    Musini, Anjaneyulu; Rao, Jayaram Prakash; Giri, Archana

    2015-10-01

    Salacia oblonga, an inhabitant of tropical regions has been used in traditional Indian medicinal systems. Phytochemicals were extracted in methanol from the plant and analyzed for various biological activities. The results of biochemical tests for total phenolics (297 ± 0.005 and 275 ± 0.006) and flavonoids (95 ± 0.004 and 61.6 ± 0.004) in the aerial and root parts were indicated as Gallic acid and quercetin equivalents respectively. The Aerial and root extracts showed strong reducing ability based on reducing power and FRAP assays. The extracts exhibited significant IC50 values in DPPH, super oxide and nitric oxide radical scavenging assays. The extracts displayed low IC50 values (<50 μg/ml) when assessed for antiproliferative activity against breast cancer cell lines using the MTT assay. GC-MS analysis of methanolic extracts have revealed the presence of compounds viz. n-Hexadecanoic acid, N-Methoxy-N-methylacetamide, Ursa-9(11), 12-dien-3-ol, Gamma-sitosterol etc., that might be potential candidates for the biological activity exhibited by the extract. PMID:26600684

  7. Biological activity of the essential oils from Cinnamodendron dinisii and Siparuna guianensis.

    PubMed

    Andrade, Milene Aparecida; Cardoso, Maria das Graças; Gomes, Marcos de Souza; de Azeredo, Camila Maria Oliveira; Batista, Luís Roberto; Soares, Maurilio José; Rodrigues, Leonardo Milani Avelar; Figueiredo, Ana Cristina S

    2015-03-01

    This study had analyzed the antibacterial, antifungal and trypanocidal activity of the essential oils from Cinnamodendron dinisii Schwacke (Canellaceae) and Siparuna guianensis Aublet (Siparunaceae). The essential oils were obtained from fresh leaves by hydrodistillation, using a modified Clevenger apparatus. Chemical analysis by gas-liquid chromatography coupled to mass spectrometry (GC-MS) showed that these essential oils are rich in monoterpene and sesquiterpene hydrocarbons. Activity against the pathogenic bacteria Escherichia coli , Listeria monocytogenes , Pseudomonas aeruginosa , Salmonella choleraesuis and Staphylococcus aureus was evaluated with the agar cavity diffusion method, while activity on the filamentous fungi Aspergillus flavus , Aspergillus niger , Aspergillus carbonarius and Penicillium commune was evaluated by the disk diffusion technique. Trypanocidal activity was tested against Trypanosoma cruzi epimastigotes, using the Tetrazolium salt (MTT) colorimetric assay. Both essential oils exhibited low inhibitory effect towards bacteria, showing high MIC values (125-500 μg mL (-1) ), with Gram positive bacteria being more susceptible. Better inhibitory effect was obtained for the evaluated fungi, with lower MIC values (7.81-250 μg mL (-1) ), being A. flavus the most susceptible species. Both essential oils presented low trypanocidal activity, with IC 50 /24 h values of 209.30 μg mL (-1) for S. guianensis and 282.93 μg mL (-1) for C. dinisii . Thus, the high values observed for the MIC of evaluated bacteria and for IC 50 /24 h of T. cruzi , suggest that the essential oils have a low inhibitory activity against these microorganisms. In addition, the low MIC values observed for the tested fungi species indicate good inhibitory activity on these microorganisms's growth. PMID:26221107

  8. Biological activity of the essential oils from Cinnamodendron dinisii and Siparuna guianensis

    PubMed Central

    Andrade, Milene Aparecida; Cardoso, Maria das Graças; Gomes, Marcos de Souza; de Azeredo, Camila Maria Oliveira; Batista, Luís Roberto; Soares, Maurilio José; Rodrigues, Leonardo Milani Avelar; Figueiredo, Ana Cristina S.

    2015-01-01

    This study had analyzed the antibacterial, antifungal and trypanocidal activity of the essential oils from Cinnamodendron dinisii Schwacke (Canellaceae) and Siparuna guianensis Aublet (Siparunaceae). The essential oils were obtained from fresh leaves by hydrodistillation, using a modified Clevenger apparatus. Chemical analysis by gas-liquid chromatography coupled to mass spectrometry (GC-MS) showed that these essential oils are rich in monoterpene and sesquiterpene hydrocarbons. Activity against the pathogenic bacteria Escherichia coli , Listeria monocytogenes , Pseudomonas aeruginosa , Salmonella choleraesuis and Staphylococcus aureus was evaluated with the agar cavity diffusion method, while activity on the filamentous fungi Aspergillus flavus , Aspergillus niger , Aspergillus carbonarius and Penicillium commune was evaluated by the disk diffusion technique. Trypanocidal activity was tested against Trypanosoma cruzi epimastigotes, using the Tetrazolium salt (MTT) colorimetric assay. Both essential oils exhibited low inhibitory effect towards bacteria, showing high MIC values (125–500 μg mL −1 ), with Gram positive bacteria being more susceptible. Better inhibitory effect was obtained for the evaluated fungi, with lower MIC values (7.81–250 μg mL −1 ), being A. flavus the most susceptible species. Both essential oils presented low trypanocidal activity, with IC 50 /24 h values of 209.30 μg mL −1 for S. guianensis and 282.93 μg mL −1 for C. dinisii . Thus, the high values observed for the MIC of evaluated bacteria and for IC 50 /24 h of T. cruzi , suggest that the essential oils have a low inhibitory activity against these microorganisms. In addition, the low MIC values observed for the tested fungi species indicate good inhibitory activity on these microorganisms’s growth. PMID:26221107

  9. [Value of electrogastrographic parameters in evaluation of gastric myoelectrical activity].

    PubMed

    Tabor, S; Thor, P J; Pitala, A; Laskiewicz, J

    1999-01-01

    Electrogastrography (EGG) is presently the only non-invasive method for the evaluation of gastric myoelectrical activity. In relation to the more and more described disturbances of the basic electrical rhythm in different pathological units EGG has been applied on a still larger scale. However, the data obtained from the EGG record do not reflect directly the gastric motility. This method allows only to make an indirect evaluation of the gastric motor disturbances. It still entails a great number of investigations so as to attain a better precisions of the evaluations of its clinical usefulness in gastroenterological diagnostics. This thesis presents the basic information on the methodology, the parameters under evaluation and the clinical application of the EGG method. PMID:10909472

  10. Antileukemic Activity of Tillandsia recurvata and Some of its Cycloartanes

    PubMed Central

    LOWE, HENRY I.C.; TOYANG, NGEH J.; WATSON, CHARAH T.; AYEAH, KENNETH N.N.; BRYANT, JOSEPH

    2015-01-01

    Background Approximately 250,000 deaths were caused by leukemia globally in 2012 and about 40%-50% of all leukemia diagnoses end-up in death. Medicinal plants are a rich source for the discovery of new drugs against leukemia and other types of cancers. To this end, we subjected the Jamaican ball moss (Tillandsia recurvata) and its cycloartanes, as well as some analogs, to in vitro screening against a number of leukemia cell lines. The WST-1 anti-proliferation assay was used to determine the anticancer activity of ball moss and two cycloartanes isolated from ball moss and four of their analogs against four leukemia cell lines (HL-60, K562, MOLM-14, monoMac6). Ball moss crude methanolic extract showed activity with a 50% inhibition concentration (IC50) value of 3.028 μg/ml against the Molm-14 cell line but was ineffective against HL-60 cells. The six cycloartanes tested demonstrated varying activity against the four leukemia cancer cell lines with IC50 values ranging from 1.83 μM to 18.3 μM. Five out of the six cycloartanes demonstrated activity, while one was inactive against all four cell lines. The preliminary activity demonstrated by the Jamaican ball moss and its cycloartanes against selected leukemia cell lines continues to throw light on the broad anticancer activity of ball moss. Further studies to evaluate the efficacy of these molecules in other leukemia cell lines are required in order to validate the activity of these molecules, as well as to determine their mechanisms of action and ascertain the activity in vivo in order to establish efficacy and safety profiles. PMID:24982361

  11. Effects of Flavonoids in Lysimachia clethroides Duby on the Activities of Cytochrome P450 CYP2E1 and CYP3A4 in Rat Liver Microsomes.

    PubMed

    Zhang, Zhi-Juan; Xia, Zhao-Yang; Wang, Jin-Mei; Song, Xue-Ting; Wei, Jin-Feng; Kang, Wen-Yi

    2016-01-01

    Incubation systems were established to investigate the effects of quercetin, kaempferol, isoquercitrin and astragalin in Lysimachia clethroides Duby on the activities of CYP2E1 and CYP3A4 in rat liver microsomes in vitro. Probe substrates of 4-nitrophenol and testosterone as well as flavonoids at different concentrations were added to the incubation systems. After incubation, a validated high performance liquid chromatography (HPLC) method was applied to separate and determine the relevant metabolites. The results suggested that kaempferol exhibited a weak inhibition of CYP2E1 activity with an IC50 of 60.26 ± 2.54 μM, while quercetin and kaempferol caused a moderate inhibition of CYP3A4 activity with IC50 values of 18.77 ± 1.69 μM and 32.65 ± 1.32 μM, respectively. Isoquercitrin and astragalin had no effects on the activities of either CYP2E1 or CYP3A4. It could be speculated from these results that the inhibitory effects of quercetin and kaempferol on the activities of CYP2E1 and CYP3A4 could be the mechanisms underlying the hepatoprotective effects of L. clethroides. PMID:27314315

  12. Antioxidant activity of twenty five plants from Colombian biodiversity.

    PubMed

    Mosquera, Oscar M; Correa, Yaned M; Buitrago, Diana C; Niño, Jaime

    2007-08-01

    The antioxidant activity of the crude n-hexane, dichloromethane, and methanol extracts from 25 species belonging to the Asteraceae, Euphorbiaceae, Rubiaceae, and Solanaceae families collected at natural reserves from the Eje Cafetero Ecorregión Colombia, were evaluated by using the spectrophotometric 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical-scavenging method. The strongest antioxidant activities were showed by the methanol and dichloromethane extracts from the Euphorbiaceae, Alchornea coelophylla (IC50 41.14 mg/l) and Acalypha platyphilla (IC50 111.99 mg/l), respectively. These two species had stronger DPPH radical scavenging activities than hydroquinone (IC50 151.19 mg/l), the positive control. The potential use of Colombian flora for their antioxidant activities is discussed. PMID:17710309

  13. Diterpenoids from aerial parts of Flickingeria fimbriata and their nuclear factor-kappaB inhibitory activities.

    PubMed

    Li, Hang; Zhao, Jing-jun; Chen, Jin-long; Zhu, Long-ping; Wang, Dong-mei; Jiang, Lin; Yang, De-po; Zhao, Zhi-min

    2015-09-01

    Chemical investigation of the aerial parts of Flickingeria fimbriata (Bl.) Hawkes resulted in isolation of sixteen ent-pimarane diterpenoids, including five rare 16-nor-ent-pimarane diterpenoids, two 15,16-dinor-ent-pimarane diterpenoids and one ent-pimarane diterpenoid. Structures were mainly elucidated by extensive spectroscopic analysis, and their absolute configurations were unequivocally determined by the exciton chirality method, the modified Mosher's method, the CD experiments (including Snatzke's method) and chemical transformations, respectively. All the isolated compounds were screened for inhibitory effects on the nuclear factor-kappaB (NF-κB) in lipopolysaccharide (LPS) induced murine macrophage RAW264.7 cells, using a NF-κB-dependent luciferase reporter gene assay. Several of these compounds displayed comparable or even better activities than the positive control pyrrolidinedithiocarbamate (PDTC) (IC50=26.3 μM) with IC50 values in the range of 14.7-29.2 μM and structure-activity relationships are briefly proposed. PMID:26186245

  14. In vitro cytotoxic activity of isolated acridones alkaloids from Zanthoxylum leprieurii Guill. et Perr.

    PubMed

    Ngoumfo, Rostand M; Jouda, Jean-Bosco; Mouafo, Ferdinand T; Komguem, Justin; Mbazoa, Céline D; Shiao, Tze Chieh; Choudhary, Mohammed I; Laatsch, Hartmut; Legault, Jean; Pichette, André; Roy, René

    2010-05-15

    Chemical investigation of the roots and fruits of Zanthoxylumleprieurii Guill. et Perr. led to the isolation of three new alkaloids including two acridone derivatives, 3-hydroxy-1,4-dimethoxy-10-methyl-9-acridone (2) and 3-hydroxy-1,2-dimethoxy-10-methyl-9-acridone (3) named helebelicine A and B, respectively, and one secobenzo[c]phenantridine, 10-O-demethyl-12-O-methylarnottianamide (10), together with thirteen other compounds. The structures of compounds 2, 3 and 10 as well as those of the known compounds were elucidated by using spectroscopic methods and by comparison with reported data. The brine-shrimp (artemia salina) lethality bioassay of the chloroform extract of the fruits showed modest cytotoxicity with LD(50) at 13.1microg/mL. Isolated compounds 1, 4-6 were found to be moderately active against lung carcinoma cells (A549), colorectal adenocarcinoma cells (DLD-1) and normal cells (WS1) with IC(50) values ranging from 27 to 77microM. In contrast to the positive control etoposide used, the cytotoxicity of the most active compound 4 was found to be selective against cancer cells in comparison to normal cells WS1 with IC(50) of 51+/-8microM and 4.3+/-0.4microM, respectively. PMID:20413315

  15. Allicin from garlic inhibits the biofilm formation and urease activity of Proteus mirabilis in vitro.

    PubMed

    Ranjbar-Omid, Mahsa; Arzanlou, Mohsen; Amani, Mojtaba; Shokri Al-Hashem, Seyyedeh Khadijeh; Amir Mozafari, Nour; Peeri Doghaheh, Hadi

    2015-05-01

    Several virulence factors contribute to the pathogenesis of Proteus mirabilis. This study determined the inhibitory effects of allicin on urease, hemolysin and biofilm of P. mirabilis ATCC 12453 and its antimicrobial activity against 20 clinical isolates of P. mirabilis. Allicin did not inhibit hemolysin, whereas it did inhibit relative urease activity in both pre-lysed (half-maximum inhibitory concentration, IC50 = 4.15 μg) and intact cells (IC50 = 21 μg) in a concentration-dependent manner. Allicin at sub-minimum inhibitory concentrations (2-32 μg mL(-1)) showed no significant effects on the growth of the bacteria (P > 0.05), but it reduced biofilm development in a concentration-dependent manner (P < 0.001). A higher concentration of allicin was needed to inhibit the established biofilms. Using the microdilution technique, the MIC90 and MBC90 values of allicin against P. mirabilis isolates were determined to be 128 and 512 μg mL(-1), respectively. The results suggest that allicin could have clinical applications in controlling P. mirabilis infections. PMID:25837813

  16. Analysis of pyrrolizidine alkaloids and evaluation of some biological activities of Algerian Senecio delphinifolius (Asteraceae).

    PubMed

    Tidjani, Soukaina; Okusa, Philippe N; Zellagui, Amar; Banuls, Laetitia Moreno Y; Stévigny, Caroline; Duez, Pierre; Rhouati, Salah

    2013-04-01

    Although Senecio species are known as sources of potentially toxic pyrrolizidine alkaloids (PAs), some species of this genus are traditionally used as remedies, notably in Algeria. In this paper, the evaluation of biological activities and the analysis of PAs of Algerian specimens of Senecio delphinifolius Vahl are reported. The n-butanolic extract of the herb showed a weak antibacterial effect against Escherichia coli with a MIC of 1 mg/mL, but was inactive against Staphylococcus aureus and Pseudomonas aeruginosa. The n-butanolic extracts of the roots, stems and herb showed a modest antioxidant activity, scavenging the free radical DPPH with respective IC50 values of 55.3, 50.2 and 13.3 microg/mL. A cytotoxic effect against a series of human tumor cell lines was observed with the n-butanolic extract from stems (IC50 ranging between 34 and 88 microg/mL). The herb of the evaluated sample contains 140 ppm of PAs (senecionine, seneciphylline, integerrimine, senkirkine) and PA-related alkaloids (dehydrosenkirkine and neosenkirkine). As the major PAs belong to the toxic series (1,2-unsaturation in the pyrrolizidine cycle and macrocyclic diester), the use of S. delphinifolius should be discouraged in traditional medicine. PMID:23738446

  17. Sulfation of β-chitosan and evaluation of biological activity from gladius of Sepioteuthis lessoniana.

    PubMed

    Subhapradha, Namasivayam; Ramasamy, Pasiyappazham; Srinivasan, Alagiri; Madeswaran, Perumal; Shanmugam, Vairamani; Shanmugam, Annaian

    2013-11-01

    β-Chitosan extracted from the gladius of Sepioteuthis lessoniana was sulfated with chlorosufonic acid. The structural features of sulfated chitosan were analyzed by NMR spectroscopy. The elemental composition was analyzed using elemental analyzer. The molecular weight of sulfated chitosan estimated through viscometry was calculated as 12.47 × 10(4) Da. The water solubility of sulfated chitosan was found to be 81%. The sulfated chitosan was able to scavenge the DPPH, superoxide and hydroxyl radicals and the inhibitory concentration (IC50) of those free radicals was found to be 4, 0.428 and 0.473 mg/ml respectively. Sulfated chitosan also showed reducing and chelating property. The IC50 value of reducing and chelating ability was found to be 0.316 and 5.64 mg/ml respectively. The anticoagulant activity was determined for human plasma with respect to activated partial thromboplastin time and prothrombin time and it was 7.13 IU and 1.26 IU, respectively. PMID:24064206

  18. Structure-activity relationship of hybrids of Cinchona alkaloids and bile acids with in vitro antiplasmodial and antitrypanosomal activities.

    PubMed

    Leverrier, Aurélie; Bero, Joanne; Cabrera, Julián; Frédérich, Michel; Quetin-Leclercq, Joëlle; Palermo, Jorge A

    2015-07-15

    In this work, a series of hybrid compounds were tested as antiparasitic substances. These hybrids were prepared from bile acids and a series of antiparasitic Cinchona alkaloids by the formation of a covalent C-C bond via a decarboxylative Barton-Zard reaction between the two entities. The bile acids showed only weak antiparasitic properties, but all the hybrids exhibited high in vitro activities (IC50: 0.48-5.39 μM) against Trypanosoma brucei. These hybrids were more active than their respective parent alkaloids (up to a 135 fold increase in activity), and displayed good selectivity indices. Aditionally, all these compounds inhibited the in vitro growth of a chloroquine-sensitive strain of Plasmodium falciparum (3D7: IC50: 36.1 nM to 8.72 μM), and the most active hybrids had IC50s comparable to that of artemisinin (IC50: 36 nM). Some structure-activity relationships among the group of 48 hybrids are discussed. The increase in antiparasitic activity may be explained by an improvement in bioavailability, since the more lipophilic derivatives showed the lowest IC50s. PMID:26063305

  19. Antioxidant activity and cytotoxicity on tumour cells of the essential oil from Cedronella canariensis var. canariensis (L.) Webb & Berthel. (Lamiaceae).

    PubMed

    Zorzetto, Christian; Sánchez-Mateo, Candelaria C; Rabanal, Rosa M; Lupidi, Giulio; Bramucci, Massimo; Quassinti, Luana; Iannarelli, Romilde; Papa, Fabrizio; Maggi, Filippo

    2015-01-01

    Cedronella canariensis is a lemon-scented species of the family Lamiaceae endemic to the Canary Islands where it is used in the traditional medicine to prepare infusions or inhalations for anti-catarrhal, tonic, diuretic, hypoglycaemiant, hypotensive, anti-inflammatory and decongestant of the respiratory tract. In this work we investigated for the first time the antioxidant activity of the essential oil and its inhibitory effects on tumour cells (A375, MDA-MB-231, HCT 116) proliferation by DPPH, ABTS, FRAP and MTT assays, respectively. The oil, analysed by GC-ionisation flame detector and GC-MS, was characterised by pinocarvone (58.0%) and β-pinene (10.8%) as the major constituents, being typical of the chemotype 'canariensis'. Noteworthy was the cytotoxic activity of the oil against the tumour cells examined, with IC50 values of 4.3, 7.3 and 11.4 μg/mL on A375, MDA-MB-231 and HCT 116 tumour cells, respectively, as well as the scavenging activity against the ABTS radical (IC50 of 10.5 μg/mL). PMID:25560780

  20. Similar Biological Activities of Two Isostructural Ruthenium and Osmium Complexes

    SciTech Connect

    Maksimoska,J.; Williams, D.; Atilla-Gokcumen, G.; Smalley, K.; Carroll, P.; Webster, R.; Filippakopoulos, P.; Knapp, S.; Herlyn, M.; Meggers, E.

    2008-01-01

    In this study, we probe and verify the concept of designing unreactive bioactive metal complexes, in which the metal possesses a purely structural function, by investigating the consequences of replacing ruthenium in a bioactive half-sandwich kinase inhibitor scaffold by its heavier congener osmium. The two isostructural complexes are compared with respect to their anticancer properties in 1205?Lu melanoma cells, activation of the Wnt signaling pathway, IC50 values against the protein kinases GSK-3? and Pim-1, and binding modes to the protein kinase Pim-1 by protein crystallography. It was found that the two congeners display almost indistinguishable biological activities, which can be explained by their nearly identical three-dimensional structures and their identical mode of action as protein kinase inhibitors. This is a unique example in which the replacement of a metal in an anticancer scaffold by its heavier homologue does not alter its biological activity.

  1. Chemical constituents from Swietenia macrophylla bark and their antioxidant activity.

    PubMed

    Falah, S; Suzuki, T; Katayama, T

    2008-08-15

    Chemical constituents of the bark of Swietenia macrophylla King (Meliaceae) was investigated not only to develop further bark utilization but also to understand the biochemical function of the bark in the forest environment. A new phenylpropanoid-substituted catechin, namely, swietemacrophyllanin [(2R*,3S*,7"R*)-catechin-8,7"-7,2"-epoxy-(methyl 4",5"-dihydroxyphenylpropanoate)] (1) was isolated from the bark of S. macrophylla together with two known compounds, catechin (2) and epicatechin (3). The structure of 1 was elucidated by spectroscopic data and by comparison of the NMR data with those of catiguanins A and B, phenylpropanoid-substituted epicatechins. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity of the isolated compounds indicated that all of the three compounds have strong activity compared with trolox as a reference. Swietemacrophyllanin (1) had the strongest activity with a 50% inhibitory concentration (IC50) value of 56 microg mL(-1). PMID:19266907

  2. Structure based activity prediction of HIV-1 reverse transcriptase inhibitors.

    PubMed

    de Jonge, Marc R; Koymans, Lucien M H; Vinkers, H Maarten; Daeyaert, Frits F D; Heeres, Jan; Lewi, Paul J; Janssen, Paul A J

    2005-03-24

    We have developed a fast and robust computational method for prediction of antiviral activity in automated de novo design of HIV-1 reverse transcriptase inhibitors. This is a structure-based approach that uses a linear relation between activity and interaction energy with discrete orientation sampling and with localized interaction energy terms. The localization allows for the analysis of mutations of the protein target and for the separation of inhibition and a specific binding to the enzyme. We apply the method to the prediction of pIC(50) of HIV-1 reverse transcriptase inhibitors. The model predicts the activity of an arbitrary compound with a q(2) of 0.681 and an average absolute error of 0.66 log value, and it is fast enough to be used in high-throughput computational applications. PMID:15771460

  3. Inhibition of Angiotensin-Converting Enzyme Activity by Flavonoids: Structure-Activity Relationship Studies

    PubMed Central

    Guerrero, Ligia; Castillo, Julián; Quiñones, Mar; Garcia-Vallvé, Santiago; Arola, Lluis; Pujadas, Gerard; Muguerza, Begoña

    2012-01-01

    Previous studies have demonstrated that certain flavonoids can have an inhibitory effect on angiotensin-converting enzyme (ACE) activity, which plays a key role in the regulation of arterial blood pressure. In the present study, 17 flavonoids belonging to five structural subtypes were evaluated in vitro for their ability to inhibit ACE in order to establish the structural basis of their bioactivity. The ACE inhibitory (ACEI) activity of these 17 flavonoids was determined by fluorimetric method at two concentrations (500 µM and 100 µM). Their inhibitory potencies ranged from 17 to 95% at 500 µM and from 0 to 57% at 100 µM. In both cases, the highest ACEI activity was obtained for luteolin. Following the determination of ACEI activity, the flavonoids with higher ACEI activity (i.e., ACEI >60% at 500 µM) were selected for further IC50 determination. The IC50 values for luteolin, quercetin, rutin, kaempferol, rhoifolin and apigenin K were 23, 43, 64, 178, 183 and 196 µM, respectively. Our results suggest that flavonoids are an excellent source of functional antihypertensive products. Furthermore, our structure-activity relationship studies show that the combination of sub-structures on the flavonoid skeleton that increase ACEI activity is made up of the following elements: (a) the catechol group in the B-ring, (b) the double bond between C2 and C3 at the C-ring, and (c) the cetone group in C4 at the C-ring. Protein-ligand docking studies are used to understand the molecular basis for these results. PMID:23185345

  4. Antileishmanial activity in Israeli plants.

    PubMed

    El-On, J; Ozer, L; Gopas, J; Sneir, R; Enav, H; Luft, N; Davidov, G; Golan-Goldhirsh, A

    2009-06-01

    Leishmaniasis is a vector-borne disease caused by flagellated protozoan parasites of the genus Leishmania, which affects both humans and other mammals. Most of the available drugs against the disease are toxic and parasite resistance to some of the drugs has already developed. In the present study, the leishmanicidal activities of methanolic extracts of some Israeli plants have been evaluated in vitro, against the free-living promastigotes and intracellular amastigotes of Leishmania major. Of the 41 extracts examined, those of two plants (Nuphar lutea>Withania somnifera) were highly effective (with a maximum inhibitory effect of >50%), those of three other species (Pteris vittata>Smyrnium olusatrum>Trifolium clypeatum) were moderately effective (25%-50%) and another four extracts (Erodium malacoides>Hyparrhenia hirta>Thymelaea hirsuta>Pulicaria crispa) showed a marginal effect (15%-22%) against the parasites. Extracts of nine plant species therefore showed antileishmanial activity but only the extract of N. lutea, used at 1.25 microg/ml, eliminated all the intracellular parasites within 3 days of treatment, with no detectable toxicity to the host macrophages. The mean (S.D.) values recorded for the median inhibitory concentrations of this extract (IC50) against the promastigotes [2.0 (0.12) microg/ml] and amastigotes [0.65 (0.023) microg/ml] and the median lethal concentration (LD50) against macrophages [2.1 (0.096) microg/ml] were encouraging, giving a therapeutic selectivity index [LD50/IC50 for amastigotes)] of 3.23. The extract of N. lutea was, in fact, generally as effective as the paromomycin that was used as the 'gold standard' drug. These results indicate that N. lutea and probably also Withania somnifera might be potential sources of clinically useful, antileishmanial compounds. PMID:19508747

  5. Inhibitory effect of mitragynine on human cytochrome P450 enzyme activities

    PubMed Central

    Hanapi, N. A.; Ismail, S.; Mansor, S. M.

    2013-01-01

    Context: To date, many findings reveal that most of the modern drugs have the ability to interact with herbal drugs. Aims: This study was conducted to determine the inhibitory effects of mitragynine on cytochrome P450 2C9, 2D6 and 3A4 activities. Methods and Material: The in vitro study was conducted using a high-throughput luminescence assay. Statistical Analysis: Statistical analysis was conducted using one-way ANOVA and Dunnett's test with P < 0.05 vs. control. The IC50 values were calculated using the GraphPad Prism® 5 (Version 5.01, GraphPad Software, Inc., USA). Results: Assessment using recombinant enzymes showed that mitragynine gave the strongest inhibitory effect on CYP2D6 with an IC50 value of 0.45±0.33 mM, followed by CYP2C9 and CYP3A4 with IC50 values of 9.70±4.80 and 41.32±6.74 μM respectively. Positive inhibitors appropriate for CYP2C9, CYP2D6, and CYP3A4 which are sulfaphenazole, quinidine and ketoconazole were used respectively. Vmax values of CYP2C9, CYP2D6 and CYP3A4 were 0.0005, 0.01155 and 0.0137 μM luciferin formed/pmol/min respectively. Km values of CYP2C9, CYP2D6, and CYP3A4 were 32.65, 56.01, and 103.30 μM respectively. Mitragynine noncompetitively inhibits CYP2C9 and CYP2D6 activities with the Ki values of 61.48 and 12.86 μM respectively. On the other hand, mitragynine inhibits CYP3A4 competitively with a Ki value of 379.18 μM. Conclusions: The findings of this study reveal that mitragynine might inhibit cytochrome P450 enzyme activities, specifically CYP2D6. Therefore, administration of mitragynine together with herbal or modern drugs which follow the same metabolic pathway may contribute to herb-drug interactions. PMID:24174816

  6. Synthesis, characterization, antiamoebic activity and toxicity of novel bisdioxazole derivatives.

    PubMed

    Iqbal, Prince Firdoos; Parveen, Humaira; Bhat, Abdul Roouf; Hayat, Faisal; Azam, Amir

    2009-11-01

    Cyclization of benzene-1,4-dicarbaldehyde dioxime 1 with different aromatic aldehydes in inert atmosphere yielded the corresponding new bisdioxazoles 2-11. The structure of 2-11 was elucidated by spectral data. In vitro antiamoebic activity was performed against HM1:IMSS strain of Entamoeba histolytica. The results showed that the compounds 3 (IC(50)=1.22 microM), 4 (IC(50)=1.41 microM), 7 (IC(50)=1.05 microM) and 10 (IC(50)=1.01 microM) exhibited better antiamoebic activity than the standard drug metronidazole (IC(50)=1.80 microM). The compounds 3, 4, 7 and 10 were tested for toxicity by MTT assay on H9c2 cardiac myoblasts and the results showed that the compounds 3, 4, 7 and 10 offered remarkable viability of 96.2%, 83.5%, 82% and 89%, respectively at a concentration of 12.5 microg/ml. PMID:19589625

  7. Synergistic activities of a silver(I) glutamic acid complex and reactive oxygen species (ROS): a novel antimicrobial and chemotherapeutic agent.

    PubMed

    Batarseh, K I; Smith, M A

    2012-01-01

    The antimicrobial and chemotherapeutic activities of a silver(I) glutamic acid complex with the synergistic concomitant generation of reactive oxygen species (ROS) were investigated here. The ROS generation system employed was via Fenton chemistry. The antimicrobial and chemotherapeutic activities were investigated on Staphylococcus aureus ATCC 43300 and Escherichia coli bacteria, and Vero and MCF-7 tumor cell lines, respectively. Antimicrobial activities were conducted by determining minimum inhibitory concentration (MIC), while chemotherapeutic efficacies were done by serial dilution using standard techniques to determine the half maximal inhibitory concentration (IC50). The antimicrobial and chemotherapeutic results obtained were compared with positive control drugs gentamicin, oxacillin, penicillin, streptomycin and cisplatin, a ubiquitously used platinum-based antitumor drug, and with the silver(I) glutamic acid complex and hydrogen peroxide separately. Based on MIC and IC50 values, it was determined that this synergistic approach was very effective at extremely low concentrations, especially when compared with the other drugs evaluated here. This finding might be of great significance regarding metronomic dosing when this synergistic approach is clinically implemented. Since silver at low concentrations exhibits no toxic, mutagenic and carcinogenic activities, this might offer an alternative approach for the development of safer silver-based antimicrobial and chemotherapeutic drugs, thereby reducing or even eliminating the toxicity associated with current drugs. Accordingly, the present approach might be integrated into the systemic clinical treatment of infectious diseases and cancer. PMID:22680634

  8. Effects of tetrandrine and closely related bis-benzylisoquinoline derivatives on cytosolic Ca2+ in human leukaemic HL-60 cells: a structure-activity relationship study.

    PubMed

    Leung, Y M; Berdik, M; Kwan, C Y; Loh, T T

    1996-08-01

    1. Previously it has been shown that tetrandrine (TET), a bis-benzylisoquinoline alkaloid, isolated from a Chinese herb Stephania tetrandra, can block non-voltage-operated Ca2+ entry activated by intracellular Ca2+ store depletion induced by thapsigargin (TSG) and can release intracellular Ca2+ in HL-60 cells. The present study attempted to identify the chemical group(s) of the TET molecule responsible for these dual effects. The effects of TET and its closely related analogues, hernandezine (HER) and berbamine (BER), on Ca2+ entry and Ca2+ release were compared in fura-2-loaded HL-60 cells. 2. Berbamine was much less potent (IC50 = 200 mumol/L) than TET and HER (both IC50 values = 25 mumol/L) in inhibiting Ca2+ entry activated by TSG. Furthermore, at 100 mumol/L, BER was much less effective than TET and HER in suppressing TSG-induced Mn2+ entry. At 30-100 mumol/L, BER was significantly less effective than both TET and HER in causing Ca2+ release from internal stores. However, only BER was able to cause store depletion-activated Ca2+ entry (or the so-called 'capacitative Ca2+ entry') upon Ca2+ readmission. 3. Taken together, the data from this structure-activity relationship study reveal that the -OCH3 group of one particular benzene ring of TET, which distinguishes TET from BER, in part produces the dual pharmacological actions of TET. PMID:8886484

  9. The length of the bridging chain in ansa-metallocenes influences their antiproliferative activity against triple negative breast cancer cells (TNBC).

    PubMed

    Beauperin, Matthieu; Top, Siden; Richard, Marie-Aude; Plażuk, Damian; Pigeon, Pascal; Toma, Stefan; Poláčková, Viera; Jaouen, Gérard

    2016-08-16

    In order to examine whether the length of the bridging chain in ansa-ferrocenes affects their antiproliferative activity against MDA-MB-231 triple negative breast cancer cell lines (TNBC), we synthesized derivatives of the type 1-[bis-(4-hydroxyphenyl)]methylidene-[n]ferrocenophane and 1-[(4-hydroxyphenyl)-phenyl]methylidene-[n]ferrocenophane with n = 3, 4, 5. We found that the derivatives of [3]ferrocenophane, the compounds with the shortest bridging chains, are the most active. IC50 values were 0.09 ± 0.01, 2.41 ± 0.10, and 1.85 ± 0.25 μM for the dihydroxyphenyl derivatives, with n = 3, 4, 5, respectively. These differences can be explained in terms of modification of the key metabolites (radical versus quinone methides) within the ansa series depending on the length of the bridging chain. The derivative of [5]ferrocenophane, possessing two -[bis-(4-hydroxyphenyl)]methylidene groups, was also prepared. Surprisingly, this relatively large molecule is also active (IC50 = 2.7 ± 0.3 μM). Two ruthenocenophane analogs were also synthesized. These ruthenium compounds are practically inactive against MDA-MB-231 cells. The unusual chemistry of these different compounds is discussed in terms of elucidating the mechanism underlying their diverse antiproliferative activity, and their specific advantages are evaluated. PMID:27276499

  10. Flavonoids from the buds of Rosa damascena inhibit the activity of 3-hydroxy-3-methylglutaryl-coenzyme a reductase and angiotensin I-converting enzyme.

    PubMed

    Kwon, Eun-Kyung; Lee, Dae-Young; Lee, Hyungjae; Kim, Dae-Ok; Baek, Nam-In; Kim, Young-Eon; Kim, Hae-Yeong

    2010-01-27

    Rosa damascena has been manufactured as various food products, including tea, in Korea. A new flavonoid glycoside, kaempferol-3-O-beta-D-glucopyranosyl(1-->4)-beta-D-xylopyranoside, named roxyloside A was isolated from the buds of this plant, along with four known compounds, isoquercitrin, afzelin, cyanidin-3-O-beta-glucoside, and quercetin gentiobioside. The chemical structures of these compounds were determined by spectroscopic analyses, including FAB-MS, UV, IR, (1)H and (13)C NMR, DEPT, and 2D NMR (COSY, HSQC, and HMBC). All the isolated compounds except cyanidin-3-O-beta-glucoside exhibited high levels of inhibitory activity against 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase with IC(50) values ranging from 47.1 to 80.6 microM. Cyanidin-3-O-beta-glucoside significantly suppressed angiotensin I-converting enzyme (ACE) activity, with an IC(50) value of 138.8 microM, while the other four compounds were ineffective. These results indicate that R. damascena and its flavonoids may be effective to improve the cardiovascular system. PMID:20038104

  11. Design, Synthesis, and Evaluation of in Vitro and in Vivo Anticancer Activity of 4-Substituted Coumarins: A Novel Class of Potent Tubulin Polymerization Inhibitors.

    PubMed

    Cao, Dong; Liu, Yibin; Yan, Wei; Wang, Chunyu; Bai, Peng; Wang, Taijin; Tang, Minghai; Wang, Xiaoyan; Yang, Zhuang; Ma, Buyun; Ma, Liang; Lei, Lei; Wang, Fang; Xu, Bixue; Zhou, Yuanyuan; Yang, Tao; Chen, Lijuan

    2016-06-23

    In this paper, a series of novel 4-substituted coumarin derivatives were synthesized. Among these compounds 34, 39, 40, 43, 62, 65, and 67 exhibited significant antiproliferative activity toward a panel of tumor cell lines at subnanomolar IC50 values. Compound 65 showed potent antiproliferative ability (IC50 values of 7-47 nM) and retained full activity in multidrug resistant cancer cells. Compound 65 caused G2/M phase arrest and interacted with the colchicine-binding site in tubulin, as confirmed by immune-fluorescence staining, microtubule dynamics assays, and competition assays with N,N'-ethylene-bis(iodoacetamide). Compound 65 reduced the cell migration and disrupted capillary-like tube formation in HUVEC cells. Importantly, compound 65 significantly and dose-dependently reduced tumor growth in four xenografts models including paclitaxel sensitive and resistant ovarian tumors (A2780s and A2780/T), adrmicycin sensitive and resistant breast tumors (MCF-7 and MCF-7/ADR), suggesting that compound 65 is a promising novel antimitotic compound for the potential treatment of cancer. PMID:27213819

  12. Improved synthesis of lysine- and arginine-derived Amadori and Heyns products and in vitro measurement of their angiotensin I-converting enzyme inhibitory activity.

    PubMed

    Srinivas, Sudhanva M; Harohally, Nanishankar V

    2012-02-15

    The L-lysine- and L-arginine-derived Amadori and Heyns products consisting of N-(1-deoxy-d-fructos-1-yl)amino acid and N-(2-deoxy-d-glucos-2-yl)amino acid were prepared by reaction of d-fructose and d-glucose with l-lysine hydrochloride and l-arginine hydrochloride using commercial zinc powder as deprotonating reagent and also as catalyst precursor in a simple synthetic route in high yield. These compounds were screened for angiotensin I-converting enzyme (ACE) inhibitory activity using a high-throughput colorimetric assay (utilizing porcine kidney ACE). The IC(50) values fall in the range of 1030-1175 μM, with N(α)-(1-deoxy-d-fructos-1-yl)arginine showing the best IC(50) value (1030 ± 38 μM). This study demonstrates an improved synthetic method for simple Amadori and Heyns products and their moderate ACE inhibitor activity. PMID:22242891

  13. A series of pyrido[2,3-b]pyrazin-3(4H)-one derivatives as aldose reductase inhibitors with antioxidant activity.

    PubMed

    Han, Zhongfei; Hao, Xin; Ma, Bing; Zhu, Changjin

    2016-10-01

    A series of pyrido[2,3-b]pyrazin-3(4H)-one based derivatives were designed as inhibitors of aldose reductase (ALR2), the enzyme which plays a key role in the development of diabetes complications as well as in the oxidative stress processes associated with diabetes and other pathologies. Most of the derivatives, having a substituted C2 aromatic group and a N4 acetic acid group on the core structure, were found to be potent and selective aldose reductase inhibitors with submicromolar IC50 values, and 9c was the most active with IC50 value 0.009 μM. Particularly, a number of the designed compounds bearing phenolic hydroxyl substituted C2-styryl side chain showed excellent not only in ALR2 inhibition but also in antioxidant, and among these 11i was proved to be the top one with an antioxidant ability even comparable to that of the well-known antioxidant Trolox. Structure-activity relationship and molecular docking studies highlighted the importance of phenolic hydroxyl substituents and vinyl spacer in C2 side chain of the scaffold for the construction of efficient and multifunctional ALR2 inhibitors. PMID:27267001

  14. The antioxidant activity of Clitoria ternatea flower petal extracts and eye gel.

    PubMed

    Kamkaen, N; Wilkinson, J M

    2009-11-01

    Extracts of Clitoria ternatea (butterfly pea) flowers are used in Thailand as a component of cosmetics and the chemical composition of the flowers suggest that they may have antioxidant activity. In this study the potential antioxidant activity of C. ternatea extracts and an extract containing eye gel formulation was investigated. Aqueous extracts were shown to have stronger antioxidant activity (as measured by DPPH scavenging activity) than ethanol extracts (IC(50) values were 1 mg/mL and 4 mg/mL, respectively). Aqueous extracts incorporated in to an eye gel formulation were also shown to retain this activity, however, it was significantly less than a commercial antiwrinkle cream included for comparison. The total phenolic content was 1.9 mg/g extract as gallic acid equivalents. The data from this study support the use of C. ternatea extracts as antioxidant inclusions in cosmetic products. PMID:19367668

  15. Effects of aging on value-directed modulation of semantic network activity during verbal learning.

    PubMed

    Cohen, Michael S; Rissman, Jesse; Suthana, Nanthia A; Castel, Alan D; Knowlton, Barbara J

    2016-01-15

    While impairments in memory recall are apparent in aging, older adults show a remarkably preserved ability to selectively remember information deemed valuable. Here, we use fMRI to compare brain activation in healthy older and younger adults during encoding of high and low value words to determine whether there are differences in how older adults achieve value-directed memory selectivity. We find that memory selectivity in older adults is associated with value-related changes in activation during word presentation in left hemisphere regions that are involved in semantic processing, similar to young adults. However, highly selective young adults show a relatively greater increase in semantic network activity during encoding of high-value items, whereas highly selective older adults show relatively diminished activity during encoding of low-value items. Additionally, only younger adults showed value-related increases in activity in semantic and reward processing regions during presentation of the value cue preceding each to-be-remembered word. Young adults therefore respond to cue value more proactively than do older adults, yet the magnitude of value-related differences in cue period brain activity did not predict individual differences in memory selectivity. Thus, our data also show that age-related reductions in prestimulus activity do not always lead to inefficient performance. PMID:26244278

  16. Prediction of p38 map kinase inhibitory activity of 3, 4-dihydropyrido [3, 2-d] pyrimidone derivatives using an expert system based on principal component analysis and least square support vector machine

    PubMed Central

    Shahlaei, M.; Saghaie, L.

    2014-01-01

    A quantitative structure–activity relationship (QSAR) study is suggested for the prediction of biological activity (pIC50) of 3, 4-dihydropyrido [3,2-d] pyrimidone derivatives as p38 inhibitors. Modeling of the biological activities of compounds of interest as a function of molecular structures was established by means of principal component analysis (PCA) and least square support vector machine (LS-SVM) methods. The results showed that the pIC50 values calculated by LS-SVM are in good agreement with the experimental data, and the performance of the LS-SVM regression model is superior to the PCA-based model. The developed LS-SVM model was applied for the prediction of the biological activities of pyrimidone derivatives, which were not in the modeling procedure. The resulted model showed high prediction ability with root mean square error of prediction of 0.460 for LS-SVM. The study provided a novel and effective approach for predicting biological activities of 3, 4-dihydropyrido [3,2-d] pyrimidone derivatives as p38 inhibitors and disclosed that LS-SVM can be used as a powerful chemometrics tool for QSAR studies. PMID:26339262

  17. Platelet-activating factor (PAF) receptor binding antagonist activity of the methanol extracts and isolated flavonoids from Chromolaena odorata (L.) King and Robinson.

    PubMed

    Ling, Sui Kiong; Pisar, Mazura Md; Man, Salbiah

    2007-06-01

    The leaf, stem and root extracts of Chromolaena odorata were evaluated for their effect on platelet-activating factor (PAF) receptor binding on rabbit platelets using 3H-PAF as a ligand. The leaf extract demonstrated high PAF receptor binding inhibitory activity of 79.2+/-2.1% at 18.2 microg/ml. A total of eleven flavonoids were subsequently isolated from the active leaf extract and evaluated for their effects on PAF receptor binding. Eight of the flavonoids exhibited >50% inhibition on the binding activity at 18.2 microg/ml. These flavonoids were identified as eriodictyol 7,4'-dimethyl ether, quercetin 7,4'-methyl ether, naringenin 4'-methyl ether, kaempferol 4'-methyl ether, kaempferol 3-O-rutinoside, taxifolin 4'-methyl ether, taxifolin 7-methyl ether and quercetin 4'-methyl ether. Their IC50 values ranged from 19.5 to 62.1 microM. PMID:17541171

  18. Synthesis, antitumor activity, and structure-activity relationship of some benzo[a]pyrano[2,3-c]phenazine derivatives.

    PubMed

    Gao, Jing; Chen, Ming; Tong, Xue; Zhu, He; Yan, Hongbin; Liu, Daichun; Li, Wanjing; Qi, Shengyu; Xiao, Dake; Wang, Yongzhi; Lu, Yuanyuan; Jiang, Feng

    2015-01-01

    A series of benzo[a]pyrano[2,3-c]phenazine derivatives with a wide range of substitutions at ring C of the benzophenazine were designed and synthesized using the one-pot, four-component domino reactions. The targeted compounds were evaluated for their antitumor activities against HCT116, MCF7, HepG2 and A549 cancer cell lines in vitro. The most active compound 6{1,2,1,9} featured the CN and p-dimethylamino phenyl substituents on γ-pyran structure on ring C. Significantly, compound 6{1,2,1,9} was found to have the highest growth inhibitory activity against the HepG2 cell line with IC50 values of 6.71 µM, which was 1.6-fold more potent than positive control anticancer drug Hydroxycamptothecine (HCPT). Furthermore, structure-activity relationship (SAR) studies on the substitutions at ring C were discussed in details. PMID:26369405

  19. Benzimidazole-Based Quinazolines: In Vitro Evaluation, Quantitative Structure-Activity Relationship, and Molecular Modeling as Aurora Kinase Inhibitors.

    PubMed

    Sharma, Alka; Luxami, Vijay; Saxena, Sanjai; Paul, Kamaldeep

    2016-03-01

    A series of benzimidazole-based quinazoline derivatives with different substitutions of primary and secondary amines at the C2 position (1-12) were evaluated for their Aurora kinase inhibitory activities. All compounds except for 3 and 6 showed good activity against Aurora kinase inhibitors, with IC50 values in the range of 0.035-0.532 μM. The ligand efficiency (LE) of the compounds with Aurora A kinase was also determined. The structure-activity relationship and the quantitative structure-activity relationship revealed that the Aurora inhibitory activities of these derivatives primarily depend on the different substitutions of the amine present at the C2 position of the quinazoline core. Molecular docking studies in the active binding site also provided theoretical support for the experimental biological data acquired. The current study identifies a novel class of Aurora kinase inhibitors, which can further be used for the treatment of cancer. PMID:26773437

  20. Chemical Evidence for Potent Xanthine Oxidase Inhibitory Activity of Ethyl Acetate Extract of Citrus aurantium L. Dried Immature Fruits.

    PubMed

    Liu, Kun; Wang, Wei; Guo, Bing-Hua; Gao, Hua; Liu, Yang; Liu, Xiao-Hong; Yao, Hui-Li; Cheng, Kun

    2016-01-01

    Xanthine oxidase is a key enzyme which can catalyze hypoxanthine and xanthine to uric acid causing hyperuricemia in humans. Xanthine oxidase inhibitory activities of 24 organic extracts of four species belonging to Citrus genus of the family Rutaceae were assayed in vitro. Since the ethyl acetate extract of C. aurantium dried immature fruits showed the highest xanthine oxidase inhibitory activity, chemical evidence for the potent inhibitory activity was clarified on the basis of structure identification of the active constituents. Five flavanones and two polymethoxyflavones were isolated and evaluated for inhibitory activity against xanthine oxidase in vitro. Of the compounds, hesperetin showed more potent inhibitory activity with an IC50 value of 16.48 μM. For the first time, this study provides a rational basis for the use of C. aurantium dried immature fruits against hyperuricemia. PMID:26950105

  1. Asperpyrone-Type Bis-Naphtho-γ-Pyrones with COX-2-Inhibitory Activities from Marine-Derived Fungus Aspergillus niger.

    PubMed

    Fang, Wei; Lin, Xiuping; Wang, Jianjiao; Liu, Yonghong; Tao, Huaming; Zhou, Xuefeng

    2016-01-01

    Bis-naphtho-γ-pyrones (BNPs) are an important group of aromatic polyketides derived from fungi, and asperpyrone-type BNPs are produced primarily by Aspergillus species. The fungal strain Aspergillus niger SCSIO Jcsw6F30, isolated from a marine alga, Sargassum sp., and identified according to its morphological traits and the internal transcribed spacer (ITS) region sequence, was studied for BNPs secondary metabolisms. After HPLC/MS analysis of crude extract of the fermentation broth, 11 asperpyrone-type BNPs were obtained directly and quickly by chromatographic separation in the extract, and those isolated asperpyrone-type BNPs were structurally identified by NMR and MS analyses. All of the BNPs showed weak cytotoxicities against 10 human tumor cells (IC50 > 30 μM). However, three of them, aurasperone F (3), aurasperone C (6) and asperpyrone A (8), exhibited obvious COX-2-inhibitory activities, with the IC50 values being 11.1, 4.2, and 6.4 μM, respectively. This is the first time the COX-2-inhibitory activities of BNPs have been reported. PMID:27447606

  2. Molecular structure‐function relationship of dietary polyphenols for inhibiting VEGF‐induced VEGFR‐2 activity

    PubMed Central

    Cerezo, Ana B.; Winterbone, Mark S.; Moyle, Christina W. A.; Needs, Paul W.

    2015-01-01

    1 Scope We recently reported potent inhibition of VEGF signalling by two flavanols at sub‐micromolar concentrations, mediated by direct binding of the flavanols to VEGF. The aim of this study was to quantify the inhibitory potency and binding affinity of a wide range of dietary polyphenols and determine the structural requirements for VEGF inhibition. 2 Methods and results The concentration of polyphenol required to cause 50% inhibition (IC50) of VEGF‐dependent VEGFR‐2 activation in HUVECS was determined after pretreating VEGF with polyphenols at various concentations. Binding affinities and binding sites on VEGF were predicted using in‐silico modelling. Ellagic acid and 15 flavonoids had IC50 values ≤10 μM while 28 other polyhenols were weak/non‐inhibitors. Structural features associated with potent inhibition included 3‐galloylation, C‐ring C2=C3, total OH, B‐ring catechol, C‐ring 3‐OH of flavonoids. Potency was not associated with polyphenol hydrophobicity. There was a strong correlation between potency of inhibition and binding affinities, and all polyphenols were predicted to bind to a region on VEGF involved in VEGFR‐2 binding. 3 Conclusion Specific polyphenols bind directly to a discrete region of VEGF and inhibit VEGF signalling, and this potentially explains the associations between consumption of these polyphenols and CVD risk. PMID:26250940

  3. Virucidal activity of Colombian Lippia essential oils on dengue virus replication in vitro.

    PubMed

    Ocazionez, Raquel Elvira; Meneses, Rocio; Torres, Flor Angela; Stashenko, Elena

    2010-05-01

    The inhibitory effect of Lippia alba and Lippia citriodora essential oils on dengue virus serotypes replication in vitro was investigated. The cytotoxicity (CC50) was evaluated by the MTT assay and the mode of viral inhibitory effect was investigated with a plaque reduction assay. The virus was treated with the essential oil for 2 h at 37 masculineC before cell adsorption and experiments were conducted to evaluate inhibition of untreated-virus replication in the presence of oil. Antiviral activity was defined as the concentration of essential oil that caused 50% reduction of the virus plaque number (IC50). L. alba oil resulted in less cytotoxicity than L. citriodora oil (CC50: 139.5 vs. 57.6 microg/mL). Virus plaque reduction for all four dengue serotypes was observed by treatment of the virus before adsorption on cell. The IC50 values for L. alba oil were between 0.4-32.6 microg/mL and between 1.9-33.7 microg/mL for L. citriodora oil. No viral inhibitory effect was observed by addition of the essential oil after virus adsorption. The inhibitory effect of the essential oil seems to cause direct virus inactivation before adsorption on host cell. PMID:20512244

  4. Synthesis and cytotoxic activity of novel poly-substituted imidazo[2,1-c][1,2,4]triazin-6-amines.

    PubMed

    Akbarzadeh, Tahmineh; Noushini, Saeedeh; Taban, Somayeh; Mahdavi, Mohammad; Khoshneviszadeh, Mahsima; Saeedi, Mina; Emami, Saeed; Eghtedari, Mohammad; Sarrafi, Yaghoub; Khoshneviszadeh, Mehdi; Safavi, Maliheh; Divsalar, Kouros; Moshafi, Mohammad Hassan; Asadipour, Ali; Sabourian, Reyhaneh; Edraki, Najmeh; Firouzi, Omidreza; Miri, Ramin; Shafiee, Abbas; Foroumadi, Alireza

    2015-05-01

    A novel series of 3,4-diphenyl-7-(hetero)arylimidazo[2,1-c][1,2,4]triazin-6-amine derivatives were synthesized via three-component reaction of 5,6-diphenyl-1,2,4-triazin-3-amine, various aromatic aldehydes, and cyclohexyl isocyanide. All synthesized compounds were tested against HL60 (human promyelocytic leukemia), MOLT-4 (human T lymphoblastic leukemia), and MCF-7 (human breast adenocarcinoma) cell lines, as cytotoxic agents. The structure-activity relationships study revealed that the introduction of hydroxyl and methoxy groups on the 7-phenyl ring can modulate the cytotoxic activity of these compounds. Among the 7-aryl derivatives, 3-hydroxyphenyl and 3-hydroxy-4-methoxyphenyl derivatives (6h and 6o) were the most potent compounds against HL60 and MCF-7 cells (IC(50s) = 9.8 - 20.4 μM). However, the replacement of the 7-aryl moiety with pyridyl or furan-2-yl resulted in compounds 6p or 6r with more promising cytotoxicity against MOLT-4 cell line (IC50 values 12.1 and 13.0 μM, respectively). Also, the acridine orange/ethidium bromide staining assay in MCF-7 cells suggested that the cytotoxic activity of compound 6r occurs via apoptosis. PMID:25613858

  5. Design, synthesis, anti-tumor activity, and molecular modeling of quinazoline and pyrido[2,3-d]pyrimidine derivatives targeting epidermal growth factor receptor.

    PubMed

    Hou, Ju; Wan, Shanhe; Wang, Guangfa; Zhang, Tingting; Li, Zhonghuang; Tian, Yuanxin; Yu, Yonghuan; Wu, Xiaoyun; Zhang, Jiajie

    2016-08-01

    Three series of novel quinazoline and pyrido[2,3-d]pyrimidine derivatives were designed, synthesized and evaluated for their ability to inhibit EGFR tyrosine kinase and a panel of five human cancer cell lines (MCF-7, A549, BT-474, SK-BR-3, and MDA-MB-231). Bioassay results indicated that five of these prepared compounds (12c-12e and 13c-13d) exhibited remarkably higher inhibitory activities against EGFR and SK-BR-3 cell line. Compounds 12c and 12e displayed the most potent EGFR inhibitory activity (IC50 = 2.97 nM and 3.58 nM, respectively) and good anti-proliferative effect against SK-BR-3 cell with the IC50 values of 3.10 μM and 5.87 μM, respectively. Furthermore, molecular docking and molecular dynamics simulation studies verified that compound 12c and 12e shared similar binding pattern with gefitinib in the binding pocket of EGFR. MM-GBSA binding free energy revealed that the compound 12c and 12e have almost the same inhibitory activity against EGFR as gefitinib, and that the dominating effect of van der Waals interactions drives the binding process. PMID:27132165

  6. Synthesis and Herbicidal Activity of New Hydrazide and Hydrazonoyl Derivatives

    PubMed Central

    Šeršeň, František; Gregáň, Fridrich; Peško, Matúš; Dvoranová, Dana; Král’ová, Katarína; Matkovičová, Zuzana; Gregáň, Juraj; Donovalová, Jana

    2016-01-01

    Three new hydrazide and five new hydrazonoyl derivatives were synthesized. The chemical structures of these compounds were confirmed by 1H-NMR, IR spectroscopy and elemental analysis. The prepared compounds were tested for their activity to inhibit photosynthetic electron transport in spinach chloroplasts and growth of the green algae Chlorella vulgaris. IC50 values of these compounds varied in wide range, from a strong to no inhibitory effect. EPR spectroscopy showed that the active compounds interfered with intermediates Z•/D•, which are localized on the donor side of photosystem II. Fluorescence spectroscopy suggested that the mechanism of inhibitory action of the prepared compounds possibly involves interactions with aromatic amino acids present in photosynthetic proteins. PMID:26248070

  7. Synthesis and Herbicidal Activity of New Hydrazide and Hydrazonoyl Derivatives.

    PubMed

    Šeršeň, František; Gregáň, Fridrich; Peško, Matúš; Dvoranová, Dana; Kráľová, Katarína; Matkovičová, Zuzana; Gregáň, Juraj; Donovalová, Jana

    2015-01-01

    Three new hydrazide and five new hydrazonoyl derivatives were synthesized. The chemical structures of these compounds were confirmed by 1H-NMR, IR spectroscopy and elemental analysis. The prepared compounds were tested for their activity to inhibit photosynthetic electron transport in spinach chloroplasts and growth of the green algae Chlorella vulgaris. IC50 values of these compounds varied in wide range, from a strong to no inhibitory effect. EPR spectroscopy showed that the active compounds interfered with intermediates Z•/D•, which are localized on the donor side of photosystem II. Fluorescence spectroscopy suggested that the mechanism of inhibitory action of the prepared compounds possibly involves interactions with aromatic amino acids present in photosynthetic proteins. PMID:26248070

  8. Evaluation of the In Vitro Antiplasmodial, Antileishmanial, and Antitrypanosomal Activity of Medicinal Plants Used in Saudi and Yemeni Traditional Medicine

    PubMed Central

    Mothana, Ramzi A.; Al-Musayeib, Nawal M.; Al-Ajmi, Mohamed F.; Cos, Paul; Maes, Louis

    2014-01-01

    The antiplasmodial, antileishmanial, and antitrypanosomal activity of twenty-five medicinal plants distributed in Saudi Arabia and Yemen was evaluated. The plants were extracted with methanol and screened in vitro against erythrocytic schizonts of Plasmodium falciparum, intracellular amastigotes of Leishmania infantum and Trypanosoma cruzi, and free trypomastigotes of T. brucei. To assess selectivity, cytotoxicity was determined on MRC-5 cells. Criteria for activity were an IC50 < 10 μg/mL and high selectivity (SI). Seven plants showed interesting antiprotozoal activity in one or more models. Extracts of Caralluma penicillata and Acalypha ciliata showed fairly good activity against P. falciparum with IC50 of 6.7 and 10.8 μg/mL and adequate selectivity (SI > 9.6 and >5.9). Interesting activity against L. infantum was obtained with Verbascum bottae (IC50 of 3.2 μg/mL, SI 10.2) and Solanum glabratum (IC50 8.1 μg/mL, SI 3.4). The extracts of C. penicillata, Leucas virgata, Loranthus regularis, and V. bottae exhibited moderate activity against T. brucei (IC50 8.5, 8.1, 8.3, and 2.3 μg/mL; SI > 7.6, 7.7, 4.3, and >14.1). These results partly support the traditional use of some of the selected medicinal plants and warrant further investigations into the putative active constituents. PMID:24963330

  9. Natural Terpenoids from Ambrosia Species Are Active In Vitro and In Vivo against Human Pathogenic Trypanosomatids

    PubMed Central

    Frank, Fernanda M.; Laurella, Laura C.; Muschietti, Liliana V.; Catalán, Cesar A.; Martino, Virginia S.; Malchiodi, Emilio L.

    2013-01-01

    Among the natural compounds, terpenoids play an important role in the drug discovery process for tropical diseases. The aim of the present work was to isolate antiprotozoal compounds from Ambrosia elatior and A. scabra. The sesquiterpene lactone (STL) cumanin was isolated from A. elatior whereas two other STLs, psilostachyin and cordilin, and one sterol glycoside, daucosterol, were isolated from A. scabra. Cumanin and cordilin were active against Trypanosoma cruzi epimastigotes showing 50% inhibition concentrations (IC50) values of 12 µM and 26 µM, respectively. Moreover, these compounds are active against bloodstrean trypomastigotes, regardless of the T. cruzi strain tested. Psilostachyin and cumanin were also active against amastigote forms with IC50 values of 21 µM and 8 µM, respectively. By contrast, daucosterol showed moderate activity on epimastigotes and trypomastigotes and was inactive against amastigote forms. We also found that cumanin and psilostachyin exhibited an additive effect in their trypanocidal activity when these two drugs were tested together. Cumanin has leishmanicidal activity with growth inhibition values greater than 80% at a concentration of 5 µg/ml (19 µM), against both L. braziliensis and L. amazonensis promastigotes. In an in vivo model of T. cruzi infection, cumanin was more active than benznidazole, producing an 8-fold reduction in parasitemia levels during the acute phase of the infection compared with the control group, and more importantly, a reduction in mortality with 66% of the animals surviving, in comparison with 100% mortality in the control group. Cumanin also showed nontoxic effects at the doses assayed in vivo, as determined using markers of hepatic damage. PMID:24130916

  10. Activity-relevant similarity values for fingerprints and implications for similarity searching

    PubMed Central

    Jasial, Swarit; Hu, Ye; Vogt, Martin; Bajorath, Jürgen

    2016-01-01

    A largely unsolved problem in chemoinformatics is the issue of how calculated compound similarity relates to activity similarity, which is central to many applications. In general, activity relationships are predicted from calculated similarity values. However, there is no solid scientific foundation to bridge between calculated molecular and observed activity similarity. Accordingly, the success rate of identifying new active compounds by similarity searching is limited. Although various attempts have been made to establish relationships between calculated fingerprint similarity values and biological activities, none of these has yielded generally applicable rules for similarity searching. In this study, we have addressed the question of molecular versus activity similarity in a more fundamental way. First, we have evaluated if activity-relevant similarity value ranges could in principle be identified for standard fingerprints and distinguished from similarity resulting from random compound comparisons. Then, we have analyzed if activity-relevant similarity values could be used to guide typical similarity search calculations aiming to identify active compounds in databases. It was found that activity-relevant similarity values can be identified as a characteristic feature of fingerprints. However, it was also shown that such values cannot be reliably used as thresholds for practical similarity search calculations. In addition, the analysis presented herein helped to rationalize differences in fingerprint search performance. PMID:27127620

  11. In vitro Antioxidant and Antibacterial Activities of Methanol Extract of Kyllinga nemoralis

    PubMed Central

    Sindhu, T.; Rajamanikandan, S.; Srinivasan, P.

    2014-01-01

    The present study was designed to evaluate the antioxidant and antibacterial activity of methanol extract of Kyllinga nemoralis. Six different in vitro antioxidant assays including 2,2-diphenyl-1-picrylhydrazyl, hydroxyl radical, superoxide anion radical, hydrogen peroxide radical, ferric reducing antioxidant power assay and reducing power were carried out to ensure the scavenging effect of the plant on free radicals. In addition, total antioxidant capacity assay, total phenolic contents, tannins, flavonoids and flavonol contents of the plant were also analysed by the standard protocols. Kyllinga nemoralis exhibited high antioxidant activity on 2,2-diphenyl-1-picrylhydrazyl assay (IC50= 90 μg/ml), superoxide radical scavenging assay (IC50= 180 μg/ml) and hydrogen peroxide radical scavenging assay (IC50= 200 μg/ml), compared with standards. These observations provide comprehensible supporting evidence for the antioxidant potential of the plant extract. Reducing power (IC50= 213.16 μg/ml) and hydroxyl radical scavenging activity (IC50= 223 μg/ml) of the plant extract was remarkable. The methanol extract of K. nemoralis exhibited significant antimicrobial activity against Gram-positive human pathogenic bacteria. Standard in vitro antioxidant assays assessed the electron donating ability of the plant extract in scavenging free radicals. The inhibitory effect of the plant extract against bacterial pathogens may be due to the presence of phytochemicals. Thus, the results suggest that Kyllinga nemoralis is a potential source of antioxidants and could serve as the base for drug development. PMID:24843192

  12. Antioxidant, anti-inflammatory and anti-hyperglycaemic activities of heterocyclic homoprostanoid derivatives.

    PubMed

    Manohara Reddy, S A; Mudgal, Jayesh; Bansal, Punit; Vasanthraju, S G; Srinivasan, K K; Rao, C Mallikarjuna; Gopalan Kutty, N

    2011-01-01

    A series of 19 heterocyclic homoprostanoids were synthesized from easily available oleic and ricinoleic acids and evaluated for their possible antioxidant, anti-inflammatory and anti-hyperlipidaemic activities. Compounds with thioxo- and oxoimidazole ring (1) and (2) have shown potent antioxidant activity with IC(50) values 0.23±0.09 and 0.41±0.01mM comparable with standard ascorbic acid. Compound (3) with a quinoxaline ring showed maximum inhibition of BSA denaturation at 1mM concentration and comparable with standard diclofenac. Incorporation of electron withdrawing substitutions like chloro- and nitro-groups in the quinoxaline ring has resulted in an increase anti-inflammatory activity. Test compounds (3), (3a) and (3c) showed modest inhibition of DPP-IV in vitro. However, the unsubstituted quinoxaline (3) and substituted quinoxalines (3b and 3c) reduced plasma glucose levels indicating the presence of hypoglycemic activity. PMID:21146413

  13. Antioxidant, antimicrobial and tyrosinase inhibitory activities of xanthones isolated from Artocarpus obtusus F.M. Jarrett.

    PubMed

    Hashim, Najihah Mohd; Rahmani, Mawardi; Ee, Gwendoline Cheng Lian; Sukari, Mohd Aspollah; Yahayu, Maizatulakmal; Amin, Muhamad Aizat Mohd; Ali, Abd Manaf; Go, Rusea

    2012-01-01

    One of the most promising plants in biological screening test results of thirteen Artocarpus species was Artocarpus obtusus FM Jarrett and detailed phytochemical investigation of powdered dried bark of the plant has led to the isolation and identification of three xanthones; pyranocycloartobiloxanthone A (1), dihydroartoindonesianin C (2) and pyranocycloartobiloxanthone B (3). These compounds were screened for antioxidant, antimicrobial and tyrosinase inhibitory activities. Pyranocycloartobiloxanthone A (1) exhibited a strong free radical scavenger towards DPPH free radicals with IC50 value of 2 µg/mL with prominent discoloration observed in comparison with standard ascorbic acid, α-tocopherol and quercetin, The compound also exhibited antibacterial activity against methicillin resistant Staphylococcus aureus (ATCC3359) and Bacillus subtilis (clinically isolated) with inhibition zone of 20 and 12 mm, respectively. However the other two xanthones were found to be inactive. For the tyrosinase inhibitory activity, again compound (1) displayed strong activity comparable with the standard kojic acid. PMID:22614861

  14. Two new triterpenoid estersaponins and biological activities of Pittosporum tobira 'Variegata' (Thunb.) W. T. Aiton leaves.

    PubMed

    El Dib, Rabab A; Eskander, Jacqueline; Mohamed, Mona A; Mohammed, Nermine M

    2015-10-01

    Two new triterpenoid estersaponins (1, 2) were isolated from the leaves of Pittosporum tobira 'Variegata' (Thunb.) W. T. Aiton, along with one known saponin (3) and one known flavonoid glycoside (4). Their structures were established by different spectroscopic methods including 1D and 2D NMR, UV, as well as ESI-MS analysis. The investigated 80% aqueous methanol extract showed significant dose dependent inhibition of acetic acid induced abdominal writhing in mice. The n-butanol fraction exerted moderate antimicrobial activity against Staphylococcus aureus and Escherichia coli. In addition, it showed in vitro antioxidant activity with IC50 value (7.3 μg/ml) lower than that of the positive control ascorbic acid (11.2 μg/ml), using DPPH free radical scavenging activity method. Evaluation of its in vitro cytotoxicity showed strong activity against breast carcinoma (MCF-7), hepatocellular carcinoma (HepG2), and colon carcinoma (HCT) cell lines. PMID:26363280

  15. A New Neolignan, and the Cytotoxic and Anti-HIV-1 Activities of Constituents from the Roots of Dasymaschalon sootepense.

    PubMed

    Hongthong, Sakchai; Kuhakarn, Chutima; Jaipetch, Thaworn; Piyachaturawat, Pawinee; Jariyawat, Surawat; Suksen, Kanoknetr; Limthongkul, Jitra; Nuntasaen, Narong; Reutrakul, Vichai

    2016-06-01

    Bioassay-guided isolation from the ethyl acetate extract of Dasymaschalon sootepense roots led to the isolation of twelve compounds including a new dihydrobenzo-furan neolignan, (+)-(2S,3S)-2,3-dihydro-2-(3,4-dimethoxyphenyl)-3-methylbenzofuran-5-carbaldehyde (5), and eleven known compounds (1-4, and 6-12). The chemical structures and stereochemistry of all the isolated compounds were established by spectroscopic techniques. The known compounds 4 and 6 have been fully characterized spectroscopically, including their absolute configurations. Cytotoxic and anti-HIV-1 reverse transcriptase (RT) activities of compounds 1-3, 5 and 8-12 were determined. Among compounds screened, compounds 2, 3 and 10 displayed weak cytotoxic activity with ED50 values ranging from 9.6-47.5 μM and only compound 2 was found weakly active against HIV-1 RT with an IC50 value of 323.2 μM. PMID:27534123

  16. Using activation status of signaling pathways as mechanism-based biomarkers to predict drug sensitivity

    PubMed Central

    Amadoz, Alicia; Sebastian-Leon, Patricia; Vidal, Enrique; Salavert, Francisco; Dopazo, Joaquin

    2015-01-01

    Many complex traits, as drug response, are associated with changes in biological pathways rather than being caused by single gene alterations. Here, a predictive framework is presented in which gene expression data are recoded into activity statuses of signal transduction circuits (sub-pathways within signaling pathways that connect receptor proteins to final effector proteins that trigger cell actions). Such activity values are used as features by a prediction algorithm which can efficiently predict a continuous variable such as the IC50 value. The main advantage of this prediction method is that the features selected by the predictor, the signaling circuits, are themselves rich-informative, mechanism-based biomarkers which provide insight into or drug molecular mechanisms of action (MoA). PMID:26678097

  17. Anti-inflammatory and antioxidant activities of phenolic compounds from Desmodium caudatum leaves and stems.

    PubMed

    Li, Wei; Sun, Ya Nan; Yan, Xi Tao; Yang, Seo Young; Kim, Sohyun; Chae, Doobyeong; Hyun, Jin Won; Kang, Hee Kyoung; Koh, Young-Sang; Kim, Young Ho

    2014-06-01

    Four flavanonols (1-4), one xanthone (5), and three flavonoid glycosides (6-8), were isolated from the leaves and stems of Desmodium caudatum. Their structures were elucidated by comparing spectroscopic data with reported values. The anti-inflammatory activity of the isolated compounds was investigated in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. Among them, compounds 1 and 2 exhibited inhibitory effects on LPS-induced IL-6, IL-12 p40, and TNF-α production with IC50 values ranging from 6.0 to 29.4 μM. Compound 5 exhibited 1,1-diphenyl-2-picrylhydrazyl radical and intracellular reactive oxygen species scavenging activity in human HaCaT keratinocytes. These results warrant further studies of the potential anti-inflammatory and antioxidant benefits of compounds from D. caudatum. PMID:24026429

  18. Synthesis and Antiproliferative Activity of Steroidal Thiosemicarbazone Platinum (Pt(II)) Complexes.

    PubMed

    Huang, Yanmin; Kong, Erbin; Gan, Chunfang; Liu, Zhiping; Lin, Qifu; Cui, Jianguo

    2015-01-01

    Steroidal compounds exhibit particular physiological activities. In this paper, some steroidal thiosemicarbazones platinum (Pt(II)) complexes were synthesized by the condensation of steroidal ketones with thiosemicarbazide using estrone, chenodeoxycholic acid, and 7-deoxycholic acid as starting materials and complexation of steroidal thiosesemicarbazones with Pt(II). The complexes were characterized by IR, NMR, and MS, and their antiproliferative activities were evaluated. The results showed that some steroidal thiosemicarbazones platinum (Pt(II)) complexes displayed moderate cytotoxicity to HeLa and Bel-7404 cells. Thereinto, complex 6 showed an excellent inhibited selectivity to HeLa cells with an IC50 value of 9.2 μM and SI value of 21.7. At the same time, all compounds were almost inactive to HEK293T (normal kidney epithelial cells). The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs. PMID:26635511

  19. Synthesis and Antiproliferative Activity of Steroidal Thiosemicarbazone Platinum (Pt(II)) Complexes

    PubMed Central

    Huang, Yanmin; Kong, Erbin; Gan, Chunfang; Liu, Zhiping; Lin, Qifu; Cui, Jianguo

    2015-01-01

    Steroidal compounds exhibit particular physiological activities. In this paper, some steroidal thiosemicarbazones platinum (Pt(II)) complexes were synthesized by the condensation of steroidal ketones with thiosemicarbazide using estrone, chenodeoxycholic acid, and 7-deoxycholic acid as starting materials and complexation of steroidal thiosesemicarbazones with Pt(II). The complexes were characterized by IR, NMR, and MS, and their antiproliferative activities were evaluated. The results showed that some steroidal thiosemicarbazones platinum (Pt(II)) complexes displayed moderate cytotoxicity to HeLa and Bel-7404 cells. Thereinto, complex 6 showed an excellent inhibited selectivity to HeLa cells with an IC50 value of 9.2 μM and SI value of 21.7. At the same time, all compounds were almost inactive to HEK293T (normal kidney epithelial cells). The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs. PMID:26635511

  20. Pentacyclic hemiacetal sterol with antifouling and cytotoxic activities from the soft coral Nephthea sp.

    PubMed

    Zhang, Jun; Li, Liang-Chun; Wang, Kai-Ling; Liao, Xiao-Jian; Deng, Zhou; Xu, Shi-Hai

    2013-02-15

    A novel unusual pentacyclic hemiacetal sterol nephthoacetal (1), was isolated from soft coral Nephthea sp. The structure of this sterol was inferred from its two acetyl derivatives (2) and (3), by means of spectroscopic methods, and quantum chemical calculations. Anti-fouling activity of compounds 1-3 against Bugula neritina larvae was evaluated, sterol (1) exhibited significant inhibitory effect with EC(50) value of 2.5 μg/mL, while having low toxicity with LC(50)>25.0 μg/mL. The in vitro cytotoxic activity of compounds 1-3 against HeLa cells was also evaluated, all of them exhibited moderate cytotoxicity with IC(50) values of 12.3 (1), 10.1 (2), and 19.6 μg/mL (3), respectively. PMID:23294699

  1. Pyrophen Produced by Endophytic Fungi Aspergillus sp Isolated from Piper crocatum Ruiz and Pav Exhibits Cytotoxic Activity and Induces S Phase Arrest in T47D Breast Cancer Cells.

    PubMed

    Astuti, Puji; Erden, Willy; Wahyono; Wahyuono, Subagus; Hertiani, Triana

    2016-01-01

    Ethyl acetate extracts obtained from culture of endophytic fungi Aspergillus sp isolated from Piper crocatum Ruiz and Pav, have been shown to possess cytotoxic activity against T47D breast cancer cells. Investigations were here conducted to determine bioactive compounds responsible for the activity. Bioassay guided fractionation was employed to obtain active compounds. Structure elucidation was performed based on analysis of LC-MS, 1H-NMR, 13C-NMR, COSY, DEPT, HMQC, HMBC data. Cytotoxity assays were conducted in 96 well plates against T47D and Vero cell lines. Bioassay guided isolation and chemical investigation led to the isolation of pyrophen, a 4-methoxy-6-(1'-acetamido-2'-phenylethyl)-2H-pyran-2-one. Further analysis of its activity against T47D and Vero cells showed an ability to inhibit the growth of T47D cells with IC50 values of 9.2 μg/mL but less cytotoxicity to Vero cells with an IC50 of 109 μg/mL. This compound at a concentration of 400 ng/mL induced S-phase arrest in T47D cells. PMID:26925652

  2. Antiprotozoal activity of the constituents of Teloxys graveolens.

    PubMed

    Calzada, Fernando; Velázquez, Claudia; Cedillo-Rivera, Roberto; Esquivel, Baldomero

    2003-08-01

    Antiprotozoal activity-guided fractionation of a methanol extract of the aerial parts of Teloxys graveolens led to the isolation of one coumarinic acid derivative, melilotoside, and five flavonoids, pinocembrine, pinostrobin, chrysin, narcissin and rutin. Among them, melilotoside exhibited the most potent activity toward Entamoeba histolytica and Giardia lamblia (IC(50) 12.5 and 16.8 micro g/mL, respectively). Narcissin showed selectivity against E. histolytlica (IC(50) 17.2 micro g/mL). The results support data for the traditional use of T. graveolens in some gastrointestinal diseases. PMID:12916068

  3. Novel 3,5-bis(arylidene)-4-oxo-1-piperidinyl dimers: structure-activity relationships and potent antileukemic and antilymphoma cytotoxicity.

    PubMed

    Santiago-Vazquez, Yahaira; Das, Swagatika; Das, Umashankar; Robles-Escajeda, Elisa; Ortega, Nora M; Lema, Carolina; Varela-Ramírez, Armando; Aguilera, Renato J; Balzarini, Jan; De Clercq, Erik; Dimmock, Stephen G; Gorecki, Dennis K J; Dimmock, Jonathan R

    2014-04-22

    Novel clusters of 3,5-bis(benzylidene)-4-oxo-1-piperidinyl dimers 3-5 were evaluated against human Molt4/C8 and CEM T-lymphocytes and human HeLa cervix adenocarcinoma cells as well as murine L1210 leukemia neoplasms. Several of these compounds demons