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Trifluoromethyl phenyl diazirine derivative of 20-methylamino-ANDROST-5-EN-3β-OL: Synthesis, docking, membrane
Yaroslav V Faletrov1, Nina S Frolova2, Ludmila V Isaeva3
1Research Institute for Physical Chemical Problems, Belarusian State University, Leningradskaya str, 14, Minsk, Belarus; Faculty of Chemistry, Belarusian State University, Leningradskaya Street, 14, Minsk, Belarus; Faculty of Biology, Belarusian State University, Kurchatova Street, 10, Minsk, Belarus.
Abstract:
We have synthesized a trifluoromethyl phenyldiazirine derivative, namely N-(4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl)-20-azapregn-5-en-3β-ol (DAMDz1). In vitro assays using Saccharomyces cerevisiae demonstrated that DAMDz1 undergoes 3-O-acetylation by yeast alcohol acetyltransferase Atf2p, indicating its ability to cross the plasma membrane. A bacterial 3beta-hydroxysteroid dehydrogenase was found to convert DAMDz1 into its 3-keto derivative. In silico computations have indicated phospholipid membrane permeability of DAMDz1 and the possibility of its localization within the active sites of aforementioned enzymes and some other proteins that interact with oxysterols and aminosterols.
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