Differential binding of methyl benzimidazol 2 yl carbamate to fungal tubulin as a mechanism of resistance to this antimiotic agent in mutant strains of Aspergillus nidulans

Chemicals/CAS: benomyl, 17804-35-2; carbon 14, 14762-75-5; colchicine, 64-86-8; fuberidazole, 3878-19-1; griseofulvin, 126-07-8; mebendazole, 31431-39-7; melatonin, 73-31-4; nocodazole, 31430-18-9; parbendazole, 14255-87-9; podophyllotoxin, 518-28-5; tiabendazole, 148-79-8; vinblastine, 865-21-4; Benzimidazoles; Carbamates; Colchicine, 64-86-8;...

The role of human glutathione S-transferase isoenzymes in the formation of glutathione conjugates of the alkylating cytostatic drug thiotepa

Nonenzymatic and glutathione S-transferase (GST) catalyzed glutathione (GSH) conjugation has been postulated as a mechanism by which alkylating cytostatic drugs can be inactivated intracellularly. In this study, we describe studies on the glutathione-dependent biotransformation of thiotepa (tris(1-aziridinyl)phosphine sulfide), a trifunctional...

Covalent binding of nitrogen mustards to the cysteine-34 residue in human serum albumin

Covalent binding of various clinically important nitrogen mustards to the cysteine-34 residue of human serum albumin, in vitro and in vivo, is demonstrated. A rapid method for detection of these adducts is presented, based on liquid chromatography-tandem mass spectrometry analysis of the adducted tripeptide Cys*-Pro-Phe after digestion of the...

Structure of Rhodococcus erythropolis limonene-1,2-epoxide hydrolase reveals a novel active site

Epoxide hydrolases are essential for the processing of epoxide-containing compounds in detoxification or metabolism. The classic epoxide hydrolases have an α/β hydrolase fold and act via a two-step reaction mechanism including an enzyme-substrate intermediate. We report here the structure of the limonene-1,2-epoxide hydrolase from Rhodococcus...

Inhibition of multidrug resistance proteins MRP1 and MRP2 by a series of α,β-unsaturated carbonyl compounds

To study the possible interplay between glutathione metabolism of and MRP inhibition by thiol reactive compounds, the interactions of a series of α,β-unsaturated carbonyl compounds with multidrug resistance proteins 1 and 2 (MRP1/ABCC1 and MRP2/ABCC2) were studied. α,β-Unsaturated carbonyl compounds react with glutathione, and therefore either...

Liquid chromatography/tandem mass spectrometry detection of covalent binding of acetaminophen to human serum albumin

Covalent binding of reactive electrophilic intermediates to proteins is considered to play an important role in the processes leading to adverse drug reactions and idiosyncratic drug reactions. Consequently, both for the discovery and the development of new drugs, there is a great interest in sensitive methodologies that enable the detection of...

Generation of Bayesian prediction models for OATP-mediated drug-drug interactions based on inhibition screen of OATP1B1, OATP1B1∗15 and OATP1B3

Human organic anion-transporting polypeptide 1B1 (OATP1B1) and OATP1B3 are important hepatic uptake transporters. Early assessment of OATP1B1/1B3-mediated drug-drug interactions (DDIs) is therefore important for successful drug development. A promising approach for early screening and prediction of DDIs is computational modeling. In this study...