Modulating effect of Cu(II) complexes with enamine and tetrazole derivatives on CYP2C and CYP3A and their cytotoxic and antiproliferative properties in HepG2 spheroids

CYP2C and CYP3A cytochromes are induced by a variety of compounds affect the pharmacokinetics pharmacodynamics large number drugs. Currently, possibility using copper coordination in antitumor therapy is being actively studied. Evaluation potential interactions between new molecules P450 necessary at an early stage drug design. The aim . To study modulating effect Cu(II) complexes with enamine tetrazole derivatives on CYP2C9, CYP2C19 CYP3A4 their cytotoxic antiproliferative properties normal human lung fibroblasts MRC-5 3D model hepatocellular carcinoma HepG2. Materials methods Cytotoxic activities copper(II) – [CuL2] (1), [Cu2(bipy)2(PT)4] (2), [Cu2(phen)2(PT)4] (3), {[Cu(phen)(MT)2]∙H2O}n (4) (L anion 2-anilinomethylidene-5,5-dimethylcyclohexane-1,3-dione; PT 5-phenyltetrazolate anion; MT 5-methyltetrazolate bipy 2,2’-bipyridine; phen 1,10-phenanthroline) were examined 2D models fluorescence-based phenotypic screening. was studied targeted results expression confirmed real-time reverse transcription polymerase chain reaction (RT-PCR). Results Complex (1) increases does not CYP2C9 expression. (2) has no CYP3A. Complexes 1,10-phenatrolin (3) induce CYP3A4, inhibit do All have dose-dependent HepG2 MRC-5: compound same cell lines, selective effect. effective both models. Conclusion [Cu2(phen)2(FT)4] complex can be used as basis for creating compound, but further modification structure required to increase selectivity tumor cells.