title: First bioanalytical evaluation of nonpeptidic cage dimeric HIV-1 protease inhibitor N-benzyl 4-aryl-1,4-dihydropyridine H17: biotransformation and toxicity on Hep G2 cells.
abstract: Cage dimeric N-benzyl 4-aryl-1,4-dihydropyridine H17 is a moderate inhibitor of HIV-1 protease. As representative of an innovative and promising class of nonpeptidic HIV-1 protease inhibitors H17 was selected for the characterization of the biochemical profile of the cage dimers concerning metabolic and toxic aspects. In the first bioanalytical evaluation of H17 on Hep G2 monolayers no phase-I metabolites were found and the extent of conjugation on phase-II of biotransformation was poor due to steric hindrance of the hydroxymethylene groups. H17 was found to be nearly non-toxic. A slight noticeable influence on cell proliferation, however, did not result from apoptotic activities. Thus, first biochemical evaluation of H17 practically suggests no decrease of an in-vivo bioavailability by metabolization.
authors.affiliation: Institut für Pharmazeutische Chemie der Martin-Luther-Universität Halle-Wittenberg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Hilgeroth
authors.forename: A
authors.initials: A
authors.lastname: Langner
mesh_terms: D001711:Biotransformation; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004095:Dihydropyridines / Q000493:pharmacokinetics / Q000633:toxicity*; D016333:HIV Protease; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics* / Q000633:toxicity*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism
chemical_list: D004095:Dihydropyridines; D017320:HIV Protease Inhibitors; D004247:DNA; D007770:L-Lactate Dehydrogenase; D016333:HIV Protease