Highly Cytotoxic Copper(II) Mixed-Ligand Quinolinonato Complexes: Pharmacokinetic Properties and Interactions with Drug Metabolizing Cytochromes P450.

ABSTRACT: The effects of two anticancer active copper(II) mixed-ligand complexes of the type [Cu(qui)(mphen)]Y·H₂O, where Hqui = 2-phenyl-3-hydroxy- 1H-quinolin-4-one, mphen = bathophenanthroline, and Y = NO₃ (complex 1) or BF₄ (complex 2) on the activities of different isoenzymes of cytochrome P450 (CYP) have been evaluated. The screening revealed significant inhibitory effects of the complexes on CYP3A4/5 (IC₅₀ values were 2.46 and 4.88 μM), CYP2C9 (IC₅₀ values were 16.34 and 37.25 μM), and CYP2C19 (IC₅₀ values were 61.21 and 77.07 μM). Further, the analysis of mechanisms of action uncovered a non-competitive type of inhibition for both the studied compounds. Consequent studies of pharmacokinetic properties proved good

SUBMITTER: Medvedikova M 

PROVIDER: S-EPMC10146558 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature