Search results for "Enzyme Inhibitor"
showing 10 items of 627 documents
4-hydroxynonenal inhibits glutathione peroxidase: protection by glutathione
1999
Abstract 4-Hydroxy-2,3-trans-nonenal, a lipid peroxidation product, inhibits glutathione peroxidase in a concentration-dependent manner. The concentration providing 50% inhibition is 0.12 mM. This inhibition can be almost completely (89%) prevented by 1 mM glutathione added to the incubation mixture 30 min before 4-hydroxy-2,3-trans-nonenal or 2,3-trans-nonenal, but not by other thiol-containing antioxidants such as 0.5 mM dithiothreitol or β-mercaptoethanol. Again the addition of 1 mM glutathione, and not of 0.5 mM dithiothreitol or β-mercaptoethanol, to the enzyme 30 min after incubation with 4-hydroxy-2,3-trans-nonenal restores activity to the same extent as does the preincubation with G…
Stereoselective Synthesis of the Glycosidase Inhibitor Australine through a One-Pot, Double-Cyclization Strategy
2006
[reaction: see text] A stereocontrolled, convergent synthesis of the alkaloid australine, a glycosidase inhibitor of the pyrrolizidine class, is described. The chiral starting materials were ketone 3, derived from L-erythrulose, and alpha-alkoxy aldehyde 4, prepared from L-malic acid. A key step of the synthesis was the highly stereoselective aldol reaction between 4 and a Z boron enolate derived from 3. Another key step was the one-pot construction of the bicyclic pyrrolizidine system by means of a three-step sequence of SN2 displacements induced by benzylamine on a trimesylate precursor.
Proteolytic cleavage of soybean Bowman-Birk inhibitor monitored by means of high-performance capillary electrophoresis. Implications for the mechanis…
1996
The hydrolysis of the soybean Bowman-Birk inhibitor in the presence of catalytic amounts of bovine trypsin and the formation of the non-covalent enzyme-inhibitor complex with an equimolar amount of enzyme are monitored by means of high-performance capillary electrophoresis (HPCE). The inhibitor is cleaved in the trypsin-reactive and more slowly in the chymotrypsin-reactive subdomain. HPCE proves itself as the only reliable analytical tool to monitor these reactions in clear contrast to classical electrophoretic, chromatographic and enzymatic methods. The most efficient separation of the intact and the two active site cleaved forms of the inhibitor was achieved in borate buffer at pH 10.0. T…
A practical entry to β-aryl-β-alkyl amino alcohols: application to the synthesis of a potent BACE1 inhibitor
2012
The 1,2-addition of alkyl Grignard reagents to readily available N-tert-butanesulfinyl ketimines, bearing an α-silyloxy substituent, proceeds in high yields and excellent diastereocontrol. The utility of the present method was demonstrated by the synthesis, in enantiomerically pure form, of one recently disclosed β-secretase (BACE1) inhibitor.
Nonsteroidal Antiinflammatory Agents, XVIII: C-5 Functionalized 6,7-Diphenyl-2,3-dihydro-1H-pyrrolizines as Inhibitors of Bovine Cyclooxygenase and 5…
1994
6-(4-Chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizines with functional groups at position 5 of the heterocyclic moiety were synthesized and tested. To determine their antiinflammatory activity bovine blood was used as enzyme source for the cyclooxygenase and 5-lipoxygenase, respectively. The iminoxy acetic acid derivative and the iminotetrazole selectively inhibit the 5-lipoxygenase, all the other compounds show medium or low affinity to the active sites of cyclooxygenase and 5-lipoxygenase. In general all compounds inhibit 5-lipoxygenase more effectively than cyclooxygenase. Concerning the inhibition of 5-lipoxygenase the most active compounds found are equipotent to the corresponding pro…
Synthesis of dehydrodipeptide esters and their evaluation as inhibitors of cathepsin C
2015
The procedures for the synthesis of esters of dehydropeptides containing C-terminal (Z)-dehydrophenylalanine and dehydroalanine have been elaborated. These esters appeared to be moderate or weak inhibitors of cathepsin C, with some of them exhibiting slow-binding behavior. As shown by molecular modeling, they are rather bound at the surface of the enzyme and are not submersed in its binding cavities. Electronic supplementary material The online version of this article (doi:10.1007/s00044-015-1366-0) contains supplementary material, which is available to authorized users.
Enzyme molecular mechanism as a starting point to design new inhibitors: a theoretical study of O-GlcNAcase.
2011
O-Glycoprotein 2-acetamino-2-deoxy-β-d-glucopyranosidase (O-GlcNAcase) hydrolyzes O-linked 2-acetamido-2-deoxy-β-d-glucopyranoside (O-GlcNAc) residues from post-translationally modified serine/threonine residues of nucleocytoplasmic protein. The chemical process involves substrate-assisted catalysis, where two aspartate residues have been identified as the two key catalytic residues of O-GlcNAcase. In this report, the first step of the catalytic mechanism used by O-GlcNAcase involving substrate-assisted catalysis has been studied using a hybrid quantum mechanical/molecular mechanical (QM/MM) Molecular Dynamics (MD) calculations. The free energy profile shows that the formation of the oxazol…
Carbonic anhydrase inhibitors
1999
Reaction of 20 aromatic/heterocyclic sulfonamides containing a free amino, imino, hydrazino or hydroxyl group, with 8-quinoline-sulfonyl chloride afforded a series of water-soluble (as hydrochloride or triflate salts) compounds. The new derivatives were assayed as inhibitors of the zinc enzyme carbonic anhydrase (CA), and more precisely of three of its isozymes, CA I, II (cytosolic forms) and IV (membrane-bound form), involved in important physiological processes. Efficient inhibition was observed against all three isozymes, but especially against CA II (in nanomolar range), which is the isozyme known to play a critical role in aqueous humor secretion within the ciliary processes of the eye…
Effect of Flavonol Derivatives on the Carrageenin-Induced Paw Edema in the Rat and Inhibition of Cyclooxygenase-1 and 5-Lipoxygenase in Vitro
2000
Alkoxyflavonols were synthesized by the Algar-Flynn-Oyamada (AFO) cyclization of chalcones. Hydroxyflavonols were prepared by dealkylation of methoxyflavonols by refluxing in hydroiodic acid. The alkoxyflavonols 3-hydroxy-2-(2,3,4-trimethoxyphenyl)-4H-chromen-4-one (6), 2-(4-ethoxyphenyl)-3-hydroxy-4H-chromen-4-one (7), 2-(4-butoxyphenyl)-3-hydroxy-4H-chromen-4-one (10), and 2-(3-n-butoxyphenyl)-3-hydroxy-4H-chromen-4-one (11) as well as the trihydroxy derivative 3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4H-chromen-4-one (18) displayed high anti-inflammatory activity in carrageenin-induced rat paw edema. Additionally, the inhibition of enzymes of the arachidonic acid cascade by the derivatives w…
EnzymesIn Vitro as indicators for pesticides: An examination
1992
Pesticides—a serious problem especially for drinking water quality—frequently are potent inhibitors of enzymes in their target organisms. As the established chemical analyses of pesticides are time-consuming, complicated, and expensive, so-called screening methods are urgently needed. For this purpose the sensitivity of 13 different enzymes was tested in vitro by inhibiting their kinetic rates and/or substrate conversions by 16 pesticides (herbicides and fungicides). Because of the stabilization and resulting low sensitivity of enzymes commercially available—especially in test kits—it was necessary to vary the test conditions and to develop special methods for detecting enzymatic inhibition…