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Type Inhibitors (type + inhibitor)
Selected AbstractsElectrochemistry and XPS study of an imidazoline as corrosion inhibitor of mild steel in an acidic environmentMATERIALS AND CORROSION/WERKSTOFFE UND KORROSION, Issue 1 2009O. Olivares-Xometl Abstract The effect of 2-(2-heptadec-8-enyl-4,5-dihydro-imidazol-1-yl)-ethylamine on the corrosion behavior of mild steel in aqueous hydrochloric acid was investigated using weight loss measurements, polarization scans, electrochemical impedance, and X-ray photoelectron spectroscopy (XPS). The inhibition efficiencies and coverage degrees increased with the concentration of inhibitor but decreased proportionally with temperature. It appears that the steric hindrance of the aliphatic chain on the imidazoline ring adsorption may affect inhibitor efficiency. Polarization curves showed that the oleic imidazoline (OI) acted essentially as a mixed type inhibitor, in which the blocking of active sites occurred. As a result of film formation, impedance spectra revealed a considerable increase in the charge transfer resistance as indicated by the second capacitive loop. XPS depth profile analysis observed the presence of nitrogen and carbon species on the inhibitor film, which were associated to the OI. [source] Inhibition of acetylcholinesterase activity by tea tree oil and constituent terpenoidsFLAVOUR AND FRAGRANCE JOURNAL, Issue 6 2005Mitsuo Miyazawa Abstract In vitro inhibition of bovine erythrocyte acetylcholinesterase activity by tea tree oil was investigated. The main constituents in the tea tree oil batch used for analysis of acetylcholinesterase inhibition were terpinen-4-ol (35.6%), , -terpinene (19.5%), , -terpinene (8.3%), p -cymene (7.2%) and 1,8-cineole (4.4%). AChE was measured by a colorimetric method. IC50 values were obtained for tea tree oil and , -pinene and were 51.2 and 57.1 µg[sol ]ml, respectively. Tea tree oil was found to comprise of mixed type inhibitors as the main constituents. The main constituents were competitive inhibitors. Copyright © 2005 John Wiley & Sons, Ltd. [source] A personal account of the role of peptide research in drug discovery: the case of hepatitis C,JOURNAL OF PEPTIDE SCIENCE, Issue 1 2001Antonello Pessi Abstract Although peptides themselves are not usually the end products of a drug discovery effort, peptide research often plays a key role in many aspects of this process. This will be illustrated by reviewing the experience of peptide research carried out at IRBM in the course of our study of hepatitis C virus (HCV). The target of our work is the NS3/4A protease, which is essential for maturation of the viral polyprotein. After a thorough examination of its substrate specificity we fine-tuned several substrate-derived peptides for enzymology studies, high-throughput screening and as fluorescent probes for secondary binding assays. In the course of these studies we made the key observation: that the protease is inhibited by its own cleavage products. Single analog and combinatorial optimization then derived potent peptide inhibitors. The crucial role of the NS4A cofactor was also addressed. NS4A is a small transmembrane protein, whose central domain is the minimal region sufficient for enzyme activation. Structural studies were performed with a peptide corresponding to the minimal activation domain, with a series of product inhibitors and with both. We found that NS3/4A is an induced fit enzyme, requiring both the cofactor and the substrate to acquire its bioactive conformation; this explained some puzzling results of ,serine-trap' type inhibitors. A more complete study on NS3 activation, however, requires the availability of the full-length NS4A protein. This was prepared by native chemical ligation, after sequence engineering to enhance its solubility; structural studies are in progress. Current work is focused on the P, region of the substrate, which, at variance with the P region, is not used for ground state binding to the enzyme and might give rise to inhibitors showing novel interactions with the enzyme. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd. [source] Stability and hydrolysis kinetics of spirosuccinimide type inhibitors of aldose reductase in aqueous solution and retardation of their hydrolysis by the target enzymeJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2008Masuo Kurono Abstract The stability and the hydrolysis kinetics of spirosuccinimide type aldose reductase (AR) inhibitors, SX-3030 (racemate) and its optical enantiomers (R - and S -isomers), were investigated in aqueous solution. The hydrolysis followed pseudo-first-order kinetics and showed significant pH dependence. Maximum solution stability was observed below pH 2.4, whereas the hydrolysis was gradually catalyzed by hydroxide ion at neutral to alkaline pH while the compounds exhibiting moderate pH-independent stability at acidic to neutral conditions (pH 4,7) to enable oral administration. A pK of 3.7 was obtained from the pH-rate profile, but this kinetically derived pK is approximately 2 pH units below the pK of the parent compounds, suggesting the presence of an acidic intermediate involved in the hydrolysis process. These findings, together with structural analysis, support the notion that the hydrolysis would proceed via nucleophilic attack of a water molecule or hydroxide ion on the scissile carbonyl bond of the succinimide ring to form a succinamic acid intermediate that has a ,-keto acid structure, followed by decarboxylation to give a racemized succinimide ring-opened product. On the other hand, the interconversion of the R - and S -isomers did not occur during hydrolysis; however, the hydrolysis of the R -isomer was markedly suppressed by the target enzyme AR whereas that of the S -isomer was not, indicating a high degree of complementarity of interacting surfaces between the R -isomer and the enzyme. The results in the present study could provide useful clues for facilitating the appropriate stabilization strategies as well as for evaluating the pharmacological effects on target tissues in vivo, and suggested that the R -isomer may be a suitable candidate as AR inhibitor. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:1468,1483, 2008 [source] | ||||||||||