In-vitro metabolic profiling study of potential topoisomerase inhibitors ‘pyrazolines’ in RLMs by mass spectrometry

Abstract

Taking into consideration of the cytotoxicity and topo-IIα inhibitory activity of pyrazoline derivatives (1–3) against HCT15 cells, and known topo-IIα inhibitor, etoposide, respectively, the compounds were biotransformed in rat liver microsomes. LC-MS/MS and MALDI mass spectrometric techniques has been used for analysis. All three compounds were biotransformed into demethylated metabolites. Among three compounds, compounds 1 and 2 were biotransformed into mono-hydroxylated metabolites and compound 3 biotransformed into reduced and epoxidized metabolites. Reduced and reduced along with demethylation metabolites were identified from MALDI Orbitrap spectrometric analysis. Without NADPH or microsomes no compounds (1–3) were generated metabolites, it shows CYP450 enzymes involvement in the presence of NADPH in the metabolisms.