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Inhibition Activity (inhibition + activity)
Kinds of Inhibition Activity Selected AbstractsHuman Immunodeficiency Virus-Reverse Transcriptase Inhibition and Hepatitis C Virus RNA-Dependent RNA Polymerase Inhibition Activities of Fullerene Derivatives.CHEMINFORM, Issue 25 2005Tadahiko Mashino No abstract is available for this article. [source] Synthesis and Investigation of Tuberculosis Inhibition Activities of Some 1,2,3-Triazole Derivatives.CHEMINFORM, Issue 24 2003Kadir Dabak Abstract For Abstract see ChemInform Abstract in Full Text. [source] Trypsin Inhibition Activity of Heat-Denatured Ovomucoid: A Kinetic StudyBIOTECHNOLOGY PROGRESS, Issue 1 2004Iesel Van der Plancken A kinetic study was conducted on the effect of heating in the temperature range of 75,110 °C on the trypsin inhibition activity of ovomucoid. Heat treatment of isolated ovomucoid resulted in a time-dependent decrease in trypsin inhibition activity that could accurately be described by a first-order kinetic model. The magnitude and the temperature dependence of the rate constants was affected by the pH during heat treatment. The heat stability of ovomucoid was the lowest at pH 7.6. Heat treatments intended to decrease the trypsin inhibition activity should therefore be carried out as soon as possible after laying, because the ovomucoid was inactivated faster at the pH of fresh egg white (pH 7.6). The presence of the other egg white constituents decreased the heat stability of ovomucoid compared to that of the model system of ovomucoid in buffer, presumably by the formation of ovomucoid-lysozyme complexes in the former. [source] Tandem Michael-Addition/Cyclization Synthesis and EGFR Kinase Inhibition Activity of Pyrido[2,3-d]pyrimidin-7(8H)-ones.CHEMINFORM, Issue 44 2004Eric E. Boros Abstract For Abstract see ChemInform Abstract in Full Text. [source] Growth Inhibition Activity of Thioacetal Artemisinin Derivatives Against Human Umbilical Vein Endothelial Cells.CHEMINFORM, Issue 8 2004Sangtae Oh Abstract For Abstract see ChemInform Abstract in Full Text. [source] Synthesis and Acetylcholinesterase/Butyrylcholinesterase Inhibition Activity of 4-Amino-2,3-diaryl-5,6,7,8-tetrahydrofuro(and thieno)[2,3-b]quinolines, and 4-Amino-5,6,7,8,9-pentahydro-2,3-diphenylcyclohepta[e]furo(and thieno)[2,3-b]pyridines.CHEMINFORM, Issue 52 2002Jose L. Marco Abstract For Abstract see ChemInform Abstract in Full Text. [source] Prediction of Tyrosinase Inhibition Activity Using Atom-Based Bilinear IndicesCHEMMEDCHEM, Issue 4 2007Yovani Marrero-Ponce Prof. Abstract A set of novel atom-based molecular fingerprints is proposed based on a bilinear map similar to that defined in linear algebra. These molecular descriptors (MDs) are proposed as a new means of molecular parametrization easily calculated from 2D molecular information. The nonstochastic and stochastic molecular indices match molecular structure provided by molecular topology by using the kth nonstochastic and stochastic graph-theoretical electronic-density matrices, Mk and Sk, respectively. Thus, the kth nonstochastic and stochastic bilinear indices are calculated using Mk and Sk as matrix operators of bilinear transformations. Chemical information is coded by using different pair combinations of atomic weightings (mass, polarizability, vdW volume, and electronegativity). The results of QSAR studies of tyrosinase inhibitors using the new MDs and linear discriminant analysis (LDA) demonstrate the ability of the bilinear indices in testing biological properties. A database of 246 structurally diverse tyrosinase inhibitors was assembled. An inactive set of 412 drugs with other clinical uses was used; both active and inactive sets were processed by hierarchical and partitional cluster analyses to design training and predicting sets. Twelve LDA-based QSAR models were obtained, the first six using the nonstochastic total and local bilinear indices and the last six with the stochastic MDs. The discriminant models were applied; globally good classifications of 99.58 and 89.96,% were observed for the best nonstochastic and stochastic bilinear indices models in the training set along with high Matthews correlation coefficients (C) of 0.99 and 0.79, respectively, in the learning set. External prediction sets used to validate the models obtained were correctly classified, with accuracies of 100 and 87.78,%, respectively, yielding C values of 1.00 and 0.73. This subset contains 180 active and inactive compounds not considered to fit the models. A simulated virtual screen demonstrated this approach in searching tyrosinase inhibitors from compounds never considered in either training or predicting series. These fitted models permitted the selection of new cycloartane compounds isolated from herbal plants as new tyrosinase inhibitors. A good correspondence between theoretical and experimental inhibitory effects on tyrosinase was observed; compound CA6 (IC50=1.32,,M) showed higher activity than the reference compounds kojic acid (IC50=16.67,,M) and L -mimosine (IC50=3.68,,M). [source] Characterization of epitopes recognized by anti- Streptococcus mutans P1 monoclonal antibodiesFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2007William P. McArthur Abstract Sequences contributing to epitopes recognized by a panel of monoclonal antibodies (mAbs) against the Streptococcus mutans surface protein P1 were delineated by Western blot and enzyme-linked immunosorbent assay using a battery of deletion constructs and recombinant polypeptides. mAbs that recognize complex discontinuous epitopes reconstituted by combining the alanine-rich and proline-rich repeat domains and varying degrees of flanking sequence were identified as well as mAbs that bound epitopes contained within contiguous segments of P1. Cross-reactivity with SspA and SspB from Streptococcus gordonii is also reported. This information enables insight into the structure and function of a streptococcal adhesin and its correlates of protection and furthers our understanding of the immunomodulatory and bacterial-adherence inhibition activities of anti-P1 mAbs. [source] Angiotensin converting enzyme inhibition of fish protein hydrolysates prepared from alkaline-aided channel catfish protein isolateJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 12 2007Ann E Theodore Abstract Peptides derived from aquatic animals have been shown to have inhibitory activity against angiotensin converting enzyme (ACE), which is a key enzyme behind elevated blood pressure. In this study a catfish protein isolate was prepared and hydrolyzed to 5%, 15% and 30% degrees of hydrolysis (% DH) and soluble peptides separated from the total hydrolysate. The hydrolysate and its soluble peptide fraction were studied separately. Increased hydrolysis produced smaller peptides, with the smallest peptides remaining in the soluble fraction. Both hydrolysates and its soluble fraction had high ACE inhibition activities, from 70% to 90.6%, depending on fraction and % DH. Results suggested that there is not a simple relationship between average peptide size and extent of % DH and ACE inactivation, but clearly the soluble fraction of the hydrolysate, containing the smallest peptides, is responsible for most of the ACE inhibition activity of the hydrolysate. Hydrolysates prepared from a pure and uniform catfish protein isolate substrate do therefore show a potential for ACE inhibition and may find use as bioactive ingredients. Copyright © 2007 Society of Chemical Industry [source] Tyrosinase inhibitory constituents from the stems of Maackia faurieiPHYTOTHERAPY RESEARCH, Issue 1 2010Jeong Mi Kim Abstract Bioassay-guided investigation of the stems of Maackia fauriei led to the isolation of seven flavonoid constituents, formononetin (1), genistein (2), daidzein (3), texasin (4), tectorigenin (5), odoratin (6) and mirkoin (7). Their structures were elucidated on the basis of spectral studies as well as by comparison with literature data. Tyrosinase inhibition activities were carried out on the isolated compounds. Among these, mirkoin (7) was identified as a potent tyrosinase inhibitor. It inhibited mushroom tyrosinase with an IC50 value of 0.005,mm, which is ten times more active than kojic acid (IC50 = 0.045,mm). The inhibition kinetics, analysed by Lineweaver-Burk plots, indicated mirkoin (7) to be a competitive inhibitor of tyrosinase when l -tyrosinase was used as a substrate. The results suggest that hydroxyl groups at C-4, in the B ring of flavonoids play an important role in the tyrosinase inhibition activities. Interestingly, compounds 4,7 were isolated for the first time from this plant. Copyright © 2009 John Wiley & Sons, Ltd. [source] Design and Synthesis of 2-Phenoxynicotinic Acid Hydrazides as Anti-inflammatory and Analgesic AgentsARCHIV DER PHARMAZIE, Issue 9 2010Alireza Moradi Abstract A series of 2-phenoxynicotinic acid hydrazides were synthesized and evaluated for their analgesic and anti-inflammatory activities. Several compounds having an unsubstituted phenyl/4-pyridyl or C-4 methoxy substituent on the terminal phenyl ring showed moderate to high analgesic or anti-inflammatory activity in comparison to mefenamic acid as the reference drug. The compounds with highest anti-inflammatory activity were subjected to in vitro COX-1/COX-2 inhibition assays and showed moderate to good COX-1 and weak COX-2 inhibition activities. [source] Antitumor activity of sequence-specific alkylating agents: Pyrolle-imidazole CBI conjugates with indole linkerCANCER SCIENCE, Issue 3 2006Ken-ichi Shinohara DNA-targeting agents, including cisplatin, bleomycin and mitomycin C, are used routinely in cancer treatments. However, these drugs are extremely toxic, attacking normal cells and causing severe side effects. One important question to consider in designing anticancer agents is whether the introduction of sequence selectivity to DNA-targeting agents can improve their efficacy as anticancer agents. In the present study, the growth inhibition activities of an indole-seco 1,2,9,9a-tetrahydrocyclopropa[1,2-c]benz[1,2-e]indol-4-one (CBI) (1) and five conjugates with hairpin pyrrole-imidazole polyamides (2,6), which have different sequence specificities for DNA alkylation, were compared using 10 different cell lines. The average values of , log GI50 (50% growth inhibition concentration) for compounds 1,6 against the 10 cell lines were 8.33, 8.56, 8.29, 8.04, 8.23 and 8.83, showing that all of these compounds strongly inhibit cell growth. Interestingly, each alkylating agent caused significantly different growth inhibition patterns with each cell line. In particular, the correlation coefficients between the , log GI50 of compound 1 and its conjugates 2,6 showed extremely low values (R < 0). These results suggest that differences in the sequence specificity of DNA alkylation lead to marked differences in biological activity. Comparison of the correlation coefficients between compounds 6 and 7, with the same sequence specificity as 6, and MS-247, with sequence specificity different from 6, when used against a panel of 37 human cancer cell lines further confirmed the above hypothesis. (Cancer Sci 2006; 97: 219,225) [source] Thymol analogues with antioxidant and L-type calcium current inhibitory activityDRUG DEVELOPMENT RESEARCH, Issue 4 2005Ai-Yu Shen Abstract Thymol is a natural product, which has antioxidant activity. 4-Morpholinomethyl-2-isopropyl-5-methylphenol (THMO), and 4-Pyrrolidinomethyl-2-isopropyl- 5-methylphenol (THPY) were synthesized by reacting thymol with formaldehyde and, respectively, morpholine or pyrrolidine. Since there is a relationship between the antioxidative status and incidence of human disease, anti-superoxidation, free radical scavenger activity, and anti-lipid peroxidation of the thymol analogues were determined by xanthine oxidase inhibition, cytochrome C system with superoxide anion releasing with formyl-Met-Leu-Phe (fMLP)/cytochalasin (CB) or phorbol myristate acetate (PMA) activating pathway in human neutrophils. All compounds studied had antioxidant activity. Mannich bases derived from thymol were generally found to be more potent compounds than thymol. THMO demonstrated the greatest antioxidant activity with IC50 values for xanthine oxidase inhibition and anti-lipid peroxidation being 21±2.78 and 61.29±5.83 µM, respectively. Moreover, since oxidative stress by free radical regulates the activity of L-type Ca2+ channel, the whole-cell configuration of the patch-clamp technique was used to investigate the effect of THMO upon ionic currents within NG108-15 cells. THMO (10 µM) suppressed the peak amplitude of L-type Ca2+ inward current (ICa,L), indicating that the antioxidative potential of the thymol analogues might be related to calcium current inhibition. The present studies suggest that THMO-dependent antioxidant and calcium ion current inhibition activity may be useful in treating free radical-related disorders. Drug Dev Res 64:195,202, 2005. © 2005 Wiley-Liss, Inc. [source] Bacteria in oral secretions of an endophytic insect inhibit antagonistic fungiECOLOGICAL ENTOMOLOGY, Issue 6 2006YASMIN J. CARDOZA Abstract 1.,Colonisation of host trees by an endophytic herbivore, the spruce beetle, Dendroctonus rufipennis, is accompanied by invasion of its galleries by a number of fungal species. Four of these associated species were identified as Leptographium abietinum, Aspergillus fumigatus, Aspergillus nomius, and Trichoderma harzianum. 2.,Trichoderma and Aspergillus significantly reduced spruce beetle survival and reproduction in controlled assays. 3.,A previously undescribed behaviour was observed, in which spruce beetle adults exuded oral secretions, especially within fungus-pervaded galleries. 4.,These oral secretions inhibited the growth of fungi except A. nomius, and disrupted the morphology of the latter. Administration of these secretions indicated a dose-dependent inhibitory effect. 5.,Oral secretions cultured on microbiological media yielded substantial bacterial growth. 6.,Filter-sterilised secretions failed to inhibit fungal growth, evidence that the bacteria are responsible for the antifungal activity. 7.,Nine bacterial isolates belonging to the Actinobacteria, Firmicutes, Gammaproteobacteria, and Betaproteobacteria taxa were obtained from the secretions. 8.,Bacterial isolates showed species-specific inhibitory activity against the four fungi antagonistic to spruce beetle. The bacterium with the strongest fungal inhibition activity was the actinomycete Micrococcus luteus. 9.,The production of bark beetle secretions containing bacteria that inhibit fungal growth is a novel finding. This suggests an additional level of complexity to ecological associations among bark beetles, conifers, and microorganisms, and an important adaptation for colonising subcortical tissue. [source] An ice-binding protein from an Antarctic sea ice bacteriumFEMS MICROBIOLOGY ECOLOGY, Issue 2 2007James A. Raymond Abstract An Antarctic sea ice bacterium of the Gram-negative genus Colwellia, strain SLW05, produces an extracellular substance that changes the morphology of growing ice. The active substance was identified as a ,25-kDa protein that was purified through its affinity for ice. The full gene sequence was determined and was found to encode a 253-amino acid protein with a calculated molecular mass of 26 350 Da. The predicted amino acid sequence is similar to predicted sequences of ice-binding proteins recently found in two species of sea ice diatoms and a species of snow mold. A recombinant ice-binding protein showed ice-binding activity and ice recrystallization inhibition activity. The protein is much smaller than bacterial ice-nucleating proteins and antifreeze proteins that have been previously described. The function of the protein is unknown but it may act as an ice recrystallization inhibitor to protect membranes in the frozen state. [source] Thymol and modified atmosphere packaging to control microbiological spoilage in packed fresh cod hamburgersINTERNATIONAL JOURNAL OF FOOD SCIENCE & TECHNOLOGY, Issue 8 2009Maria Rosaria Corbo Summary A study on the use of mild technologies to produce packaged fish hamburgers was presented. In particular, the antimicrobial effect of some natural compounds (carvacrol, eugenol, thymol, green tea extract, rosemary extract, grapefruit seed extract and lemon extract), at various concentrations (500,10 000 ppm), was screened in vitro against the main fish spoilage micro-organisms (Shewanella putrefaciens and Photobacterium phosphoreum). Lemon extract and thymol, in combination with modified atmosphere packaging, showed the greatest inhibition activity, therefore, thymol was subsequently used as an ingredient for producing fish hamburgers. Results pointed out that this combination is effective in controlling the growth of microbial species mainly involved in fresh fish spoilage; in particular, it significantly (P < 0.05) reduced the growth rate of bacterial population, performing about 4.8 log CFU g,1 and 6.5 log CFU g,1 reduction of the hydrogen sulphide producing bacteria and psychrotrophic aerobic specific spoilage organisms cell load, respectively, if compared with the control. [source] Effects of juvenile hormone I, precocene I and precocene II on the progeny of Microplitis rufiventris Kok. female when administered via its host, Spodoptera littoralis (Boisd.)JOURNAL OF APPLIED ENTOMOLOGY, Issue 1 2004W. E. Khafagi Abstract: Reproductive biologies of Microplitis rufiventris Kok. females resulting from topically treated Spodoptera littoralis (Boisd.) larvae with constant effective doses of juvenile hormone I (JHI, 1 ,g), precocene I (PI, 25 ,g) or PII (25 ,g) were investigated. Although the female wasps were treated during their presence as eggs or larvae in their hosts, the complete effects of the test compound were not apparent until the wasps had become adults. On the bases of the obtained results, the reproductive inhibition activity caused by the test compounds comprises of two categories: (1) reduction in progeny production, and (2) induction of significant proportion of imperfect ,non-functional' parasitoid progeny. Whereas, the adverse effect of JHI is only restricted to the second category, the adverse effects of PI or PII fall into both categories. Thus, workers should be aware of the delayed effects of new generations of pesticides which may occur in later stages of the non-target insects. [source] Fusion core structure of the severe acute respiratory syndrome coronavirus (SARS-CoV): In search of potent SARS-CoV entry inhibitorsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 6 2008Ling-Hon Matthew Chu Abstract Severe acute respiratory coronavirus (SARS-CoV) spike (S) glycoprotein fusion core consists of a six-helix bundle with the three C-terminal heptad repeat (HR2) helices packed against a central coiled-coil of the other three N-terminal heptad repeat (HR1) helices. Each of the three peripheral HR2 helices shows prominent contacts with the hydrophobic surface of the central HR1 coiled-coil. The concerted protein,protein interactions among the HR helices are responsible for the fusion event that leads to the release of the SARS-CoV nucleocapsid into the target host-cell. In this investigation, we applied recombinant protein and synthetic peptide-based biophysical assays to characterize the biological activities of the HR helices. In a parallel experiment, we employed a HIV-luc/SARS pseudotyped virus entry inhibition assay to screen for potent inhibitory activities on HR peptides derived from the SARS-CoV S protein HR regions and a series of other small-molecule drugs. Three HR peptides and five small-molecule drugs were identified as potential inhibitors. ADS-J1, which has been used to interfere with the fusogenesis of HIV-1 onto CD4+ cells, demonstrated the highest HIV-luc/SARS pseudotyped virus-entry inhibition activity among the other small-molecule drugs. Molecular modeling analysis suggested that ADS-J1 may bind to the deep pocket of the hydrophobic groove on the surface of the central coiled-coil of SARS-CoV S HR protein and prevent the entrance of the SARS-CoV into the host cells. J. Cell. Biochem. 104: 2335,2347, 2008. © 2008 Wiley-Liss, Inc. [source] ISOLATION AND PARTIAL CHARACTERIZATION OF A NOVEL BACTERIOCIN PRODUCED BY LACTOCOCCUS LACTIS SSP.JOURNAL OF FOOD SAFETY, Issue 1 2007LACTIS MC3 ABSTRACT This work presents the isolation and partial characterization of a new lactococcal bacteriocin produced by Lactococcus lactis ssp. lactis MC38. The bacteriocin demonstrated broad spectrum of inhibition activity against both pathogenic and food spoilage organisms, and various lactic acid bacteria. This antimicrobial substance appeared to be proteinaceous because its activity was completely inactivated by proteinase K and ,-chymotrypsin. It was heat and pH stable. The apparent molecular mass of the purified bacteriocin, determined by sodium dodecyl sulfate,polyacrylamide gel electrophoresis, was 8.0 kDa. The amino acid composition of the studied bacteriocin was found to be quite different from known lactococcal bacteriocins. The calculation of the number of amino acid residues in the bacteriocin molecule revealed that it contained 62 amino acids. [source] Novel 3-benzoyl-2-piperazinylquinoxaline derivatives as potential antitumor agentsJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 3 2006Sandra Piras A series of new benzoylquinoxaline derivatives (7-26) was synthesized and evaluated for antitumor activity against a panel of 60 human cell lines at the NCI of Bethesda. Among the compounds which have passed the preliminary screening, compound 23 exhibited the best profile and growth inhibition activity at 100 - 10 ,M. The compounds were then tested towards a folate-dependent enzymes bio-library including Thymidylate synthases enzymes and human Dihydrofolate reductase at 10 ,M. The most of compounds exhibited a moderate inhibitory activity towards all or some of the enzymes tested with detectable inhibition constants (Ki) values in the range of 0.6-70 ,M. Compounds 21, 23, 24 showed Ki in the range of 10-38 ,M against both hDHFR and hTS. [source] Efficient synthesis and comparative studies of the arginine and N,,N, -dimethylarginine forms of the human nucleolin glycine/arginine rich domainJOURNAL OF PEPTIDE SCIENCE, Issue 1 2005Dr Sotir Zahariev Abstract The Gly- and Arg-rich C -terminal region of human nucleolin is a 61-residue long domain involved in a number of protein,protein and protein,nucleic acid interactions. This domain contains 10 aDma residues in the form of aDma-GG repeats interspersed with Phe residues. The exact role of Arg dimethylation is not known, partly because of the lack of efficient synthetic methods. This work describes an effective synthetic strategy, generally applicable to long RGG peptides, based on side-chain protected aDma and backbone protected dipeptide Fmoc-Gly-(Dmob)Gly-OH. This strategy allowed us to synthesize both the unmodified (N61Arg) and the dimethylated (N61aDma) peptides with high yield (,26%) and purity. As detected by NMR spectroscopy, N61Arg does not possess any stable secondary or tertiary structure in solution and N,,N, -dimethylation of the guanidino group does not alter the overall conformational propensity of this peptide. While both peptides bind single-stranded nucleic acids with similar affinities (Kd = 1.5 × 10,7M), they exhibit a different behaviour in ssDNA affinity chromatography consistent with the difference in pKa values. It has been previously shown that N61Arg inhibits HIV infection at the stage of HIV attachment to cells. This study demonstrates that Arg-dimethylated C -terminal domain lacks any inhibition activity, raising the question of whether nucleolin expressed on the cell-surface is indeed dimethylated. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source] Angiotensin converting enzyme inhibition of fish protein hydrolysates prepared from alkaline-aided channel catfish protein isolateJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 12 2007Ann E Theodore Abstract Peptides derived from aquatic animals have been shown to have inhibitory activity against angiotensin converting enzyme (ACE), which is a key enzyme behind elevated blood pressure. In this study a catfish protein isolate was prepared and hydrolyzed to 5%, 15% and 30% degrees of hydrolysis (% DH) and soluble peptides separated from the total hydrolysate. The hydrolysate and its soluble peptide fraction were studied separately. Increased hydrolysis produced smaller peptides, with the smallest peptides remaining in the soluble fraction. Both hydrolysates and its soluble fraction had high ACE inhibition activities, from 70% to 90.6%, depending on fraction and % DH. Results suggested that there is not a simple relationship between average peptide size and extent of % DH and ACE inactivation, but clearly the soluble fraction of the hydrolysate, containing the smallest peptides, is responsible for most of the ACE inhibition activity of the hydrolysate. Hydrolysates prepared from a pure and uniform catfish protein isolate substrate do therefore show a potential for ACE inhibition and may find use as bioactive ingredients. Copyright © 2007 Society of Chemical Industry [source] A 90 day repeated oral toxicity study on plantamajoside concentrate from Plantago asiaticaPHYTOTHERAPY RESEARCH, Issue 12 2007Byung-Gyu Park Abstract Plantago asiatica is distributed widely in East Asia. Since ancient times it has been used as a diuretic to treat acute urinary infections, and as an antiinflammatory, antiasthmatic, antioxidant, antibacterial, antihyperlipidemic and antihepatitis drug. The major compound, plantamajoside from P. asiatica, which is used as a marker compound in chemotaxonomic studies, was reported to have antibacterial activity, inhibition activity against cAMP phosphodiesterase and 5-lipoxygenase and antioxidant activity. However, there are no reports on the safety of plantamajoside. This study assessed the toxic effects of plantamajoside concentrate (PC), the purity of which was above 80%, in rats following administration at dose levels of 0, 500, 1000 and 2000 mg/kg body weight/day for 13 weeks, as recommended by the OECD guidelines. The results showed that there were no differences in body weight, food intake, water consumption, relative organ weight or the hematological and serum biochemical values among the different dosage groups. No death or abnormal clinical signs were observed during the experimental period. Therefore, the results suggested that no observed adverse effect level (NOAEL) of the PC in rats after oral administration is considered to be greater than 2000 mg/kg in rats under the conditions employed in this study. Copyright © 2007 John Wiley & Sons, Ltd. [source] Evaluation of antiprotozoal and plasmodial enoyl-ACP reductase inhibition potential of turkish medicinal plantsPHYTOTHERAPY RESEARCH, Issue 2 2005D. Tasdemir Abstract A total of 58 extracts of different polarity were prepared from various organs of 16 species of Turkish plants and screened for their antitrypanosomal, antileishmanial and antiplasmodial activities. No significant activity was observed against Trypanosoma cruzi, whereas many extracts showed appreciable trypanocidal potential against T. brucei rhodesiense, with the CHCl3 -soluble portion of Phlomis kurdica being the most active (IC50 2.7 µg[sol ]mL). Almost all extracts, particularly the CHCl3 phases, exhibited growth inhibition activity against Leishmania donovani amastigotes. The CHCl3 -solubles of Putoria calabrica roots (IC50 1.9 µg[sol ]mL), Wendlandia ligustroides leaves (IC50 2.1 µg[sol ]mL) and Rhododendronluteum leaves (IC50 2.3 µg[sol ]mL) displayed the highest leishmanicidal potential. The majority of the extracts also possessed antiplasmodial activity against the multi-drug resistant K1 Plasmodium falciparum strain. The most potent antiplasmodial activity was observed with the CHCl3 extracts of Phlomis kurdica (IC50 1.5 µg[sol ]mL), P. leucophracta (IC50 1.6 µg[sol ]mL), Scrophularia cryptophila (IC50 1.8 µg[sol ]mL), Morina persica (IC50 1.9 µg[sol ]mL) and the aqueous root extract of Asperula nitida subsp. subcapitellata (IC50 1.6 µg[sol ]mL). Twenty-one extracts with significant antimalarial activity (IC50 < 5 µg[sol ]mL) were also tested for their ability to inhibit the purified enoyl-ACP reductase (FabI), a crucial enzyme in the fatty acid biosynthesis of P. falciparum. The CHCl3 extract of Rhododendronungernii leaves (IC50 10 µg[sol ]mL) and the H2O-soluble portion of Rhododendronsmirnovii leaves (IC50 0.4 µg[sol ]mL) strongly inhibited the FabI enzyme. The preliminary data indicate that some (poly)phenolic compounds are responsible for the FabI inhibition potential of these extracts. The presented work reports for the first time the antiprotozoal activity of nine different genera as well as a target specific antimalarial screening for the identification of P. falciparum FabI inhibitors from medicinal plant extracts. Copyright © 2005 John Wiley & Sons, Ltd. [source] Proteome analysis of apoptosis signaling by S -trityl- L -cysteine, a potent reversible inhibitor of human mitotic kinesin Eg5PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 2 2008Frank Kozielski Abstract Mitotic kinesins represent potential drug targets for anticancer chemotherapy. Inhibitors of different chemical classes have been identified that target human Eg5, a kinesin responsible for the establishment of the bipolar spindle. One potent Eg5 inhibitor is S -trityl- L -cysteine (STLC), which arrests cells in mitosis and exhibits tumor growth inhibition activity. However, the underlying mechanism of STLC action on the molecular level is unknown. Here, cells treated with STLC were blocked in mitosis through activation of the spindle assembly checkpoint as shown by the phosphorylated state of BubR1 and the accumulation of mitosis specific phosphorylation on histone H3 and aurora A kinase. Using live cell imaging, we observed prolonged mitotic arrest and subsequent cell death after incubation of GFP-,-tubulin HeLa cells with STLC. Activated caspase-9 occurred before cleavage of caspase-8 leading to the accumulation of the activated executioner caspase-3 suggesting that STLC induces apoptosis through the intrinsic apoptotic pathway. Proteome analysis following STLC treatment revealed 33 differentially regulated proteins of various cellular processes, 31 of which can be linked to apoptotic cell death. Interestingly, four identified proteins, chromobox protein homolog, RNA-binding Src associated in mitosis 68,kDa protein, stathmin, and translationally controlled tumor protein can be linked to mitotic and apoptotic processes. [source] cGMP-enhancing- and ,1A/,1D -adrenoceptor blockade-derived inhibition of Rho-kinase by KMUP-1 provides optimal prostate relaxation and epithelial cell anti-proliferation efficacyTHE PROSTATE, Issue 13 2007Chi-Ming Liu Abstract Background Soluble guanylyl cyclase (sGC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) and Rho kinase (ROCK2) pathways are important in the regulation of prostate smooth muscle tone. This study is aimed to examine the relaxation activities of a sGC activator and PDE5A/ROCK2 inhibitor KMUP-1 in rat prostate and associated anti-proliferation activity in human prostatic epithelial cells. Methods The action characteristics of KMUP-1 were identified by isometric tension measurement, receptor binding assay, Western blotting and radioimmunoassay in rat prostate. Anti-proliferation activity of KMUP-1 in human prostatic epithelial PZ-HPV-7 cells was identified using flow cytometry and real time QRT-PCR. Results KMUP-1 inhibited phenylephrine-induced contractility in a concentration-dependent manner. KMUP-1 possessed potent ,1A/,1D -adrenoceptor binding inhibition activity, increased cAMP/cGMP levels and increased the expression of sGC, PKG, and PKA protein in rat prostate. Moreover, KMUP-1 inhibited phenylephrine-induced ROCK2 expression. KMUP-1 inhibited cell growth, arrested the cell cycle at G0/G1 phase and increased the expression of p21 in PZ-HPV-7 cells. Conclusions These results broaden our knowledge of sGC/cGMP/PKG and ROCK2 regulation on the relaxation and proliferation of prostate, which may help in the design of benign prostate hyperplasia (BPH) therapies that target these signaling pathways. KMUP-1 possesses the potential benefit in the treatment of BPH by its ,1A/,1D -adrenoceptor blockade, sGC activation, inhibition of PDE5A and ROCK2 and p21 protein enhancement, leading to attenuation of the smooth muscle tone and the proliferation of epithelial PZ-HPV-7 cells. The synergistic contribution of these pathways by KMUP-1 may benefit BPH patients with lower urinary tract symptoms. Prostate 67: 1397,1410, 2007. © 2007 Wiley-Liss, Inc. [source] Synthesis, characterization, electrochemical, catalytic and antimicrobial activity studies of hydrazone Schiff base ruthenium(II) complexesAPPLIED ORGANOMETALLIC CHEMISTRY, Issue 4 2010N. Thilagavathi Abstract Four tridentate O, N, O donor Schiff base ligands were prepared by the reaction of substituted benzhydrazide and appropriate salicylaldehyde. The complexes of these ligands were synthesized by refluxing the ligands with ruthenium(II) starting complexes of the formula [RuHCl(CO)(EPh3)2B] in benzene, where E = P or As; B = PPh3 or AsPh3 or pyridine. The newly synthesized complexes were characterized by elemental, spectral (FT-IR, UV and NMR) and electrochemical data. On the basis of the above studies, an octahedral structure has been proposed for all the complexes. The catalytic efficiency of the complexes in aryl,aryl couplings and oxidation of alcohols was examined and their inhibition activity against the growth of the micro-organisms was also examined. Copyright © 2009 John Wiley & Sons, Ltd. [source] Trypsin Inhibition Activity of Heat-Denatured Ovomucoid: A Kinetic StudyBIOTECHNOLOGY PROGRESS, Issue 1 2004Iesel Van der Plancken A kinetic study was conducted on the effect of heating in the temperature range of 75,110 °C on the trypsin inhibition activity of ovomucoid. Heat treatment of isolated ovomucoid resulted in a time-dependent decrease in trypsin inhibition activity that could accurately be described by a first-order kinetic model. The magnitude and the temperature dependence of the rate constants was affected by the pH during heat treatment. The heat stability of ovomucoid was the lowest at pH 7.6. Heat treatments intended to decrease the trypsin inhibition activity should therefore be carried out as soon as possible after laying, because the ovomucoid was inactivated faster at the pH of fresh egg white (pH 7.6). The presence of the other egg white constituents decreased the heat stability of ovomucoid compared to that of the model system of ovomucoid in buffer, presumably by the formation of ovomucoid-lysozyme complexes in the former. [source] Synthesis of N -Hydroxycinnamides Capped with a Naturally Occurring Moiety as Inhibitors of Histone DeacetylaseCHEMMEDCHEM, Issue 4 2010Wei-Jan Huang Prof. Abstract Histone deacetylase (HDAC) inhibitors are regarded as promising therapeutics for the treatment of cancer. All reported HDAC inhibitors contain three pharmacophoric features: a zinc-chelating group, a hydrophobic linker, and a hydrophobic cap for surface recognition. In this study we investigated the effectiveness of osthole, a hydrophobic Chinese herbal compound, as the surface recognition cap in hydroxamate-based compounds as inhibitors of HDAC. Nine novel osthole-based N -hydroxycinnamides were synthesized and screened for enzyme inhibition activity. Compounds 9,d, 9,e, 9,g exhibited inhibitory activities (IC50=24.5, 20.0, 19.6,nM) against nuclear HDACs in HeLa cells comparable to that of suberoylanilide hydroxamic acid (SAHA; IC50=24.5,nM), a potent inhibitor clinically used for the treatment of cutaneous T-cell lymphoma (CTCL). While compounds 9,d and 9,e showed SAHA-like activity towards HDAC1 and HDAC6, compound 9,g was more selective for HDAC1. Compound 9,d exhibited the best cellular effect, which was comparable to that of SAHA, of enhancing acetylation of either ,-tubulin or histone H3. Molecular docking analysis showed that the osthole moiety of compound 9,d may interact with the same hydrophobic surface pocket exploited by SAHA and it may be modified to provide class-specific selectivity. These results suggest that osthole is an effective hydrophobic cap when incorporated into N -hydroxycinnamide-derived HDAC inhibitors. [source] | |||||||||||||||||||||||||||||||