Cytochrome P450 inhibition potential and initial genotoxic evaluation of 14-O-[(4,6-diaminopyrimidine-2-yl)thioacetyl] mutilin.

ABSTRACT: 14-O-[(4,6-Diaminopyrimidine-2-yl)thioacetyl] mutilin (DPTM) is a promising drug candidate with excellent antibacterial activity against Gram-positive bacteria. The present study was designed to characterize its Cytochrome P450 (CYP) enzymes inhibition activities and the genotoxicity with the standard Ames test. We determined the inhibitory effects of DPTM on CYP1A2, CYP2D1/6, CYP2E1, CYP2C11/9 and CYP3A/4 in rat liver microsomes (RLMs) and in human liver microsomes (HLMs). The mRNA expressions of the above CYP isoforms and their transcriptional regulators were also evaluated using the Hep G2 cell model. The results showed DPTM exhibited a moderate inhibitory potential against CYP3A/4 (IC₅₀ values of 10 ± 2 and 8 ± 2 μM, respectively) and weak against the other CYP enzymes based

SUBMITTER: Fu Y 

PROVIDER: S-EPMC7417534 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature