Antimicrobial drugs are chemical substances (of natural or synthetic origin) that suppress the growth of (or destroy) microorganisms (e. g. antibiotics act primarily against bacteria). Copper complexes ([Cu₂(pmdien)₂(H₂O)₂(μ-fu)](ClO₄)₂ – complex No. 5; [Cu₂(pmdien)₂(H₂O)₂(μ-dtdp)](ClO₄)₂ – complex No. 6), on which this study is focused, show antibacterial activity (1). As with every promising compound, these copper complexes were tested for their potential to inhibit activities of liver microsomal cytochromes P450 (CYP) in vitro. Porcine liver microsomes served as a model system. In the first step, possible effect of these copper complexes on enzyme activity of CYP2D (bufuralol 1´ hydroxylation) was determined. Copper complexes decreased enzyme activity of CYP2D to 1 % (IC_{50 complex No. 5} = 3.4 μmol.l^-1), 4 % (IC5_{0 complex No. 6} = 24.9 μmol.l^-1), respectively, at 50 μmol.l^-1 concentration of individual complexes in the reaction mixture. The Dixon plots and Lineweaver–Burk plots indicate most probably a partially noncompetitive inhibition in both cases. Verification of this interaction was confirmed with human liver microsomal CYP2D6. Enzyme activity of human CYP2D6 was affected too (decrease to 0 % of activity in both cases at 50 μmol.l^-1 concentration of individual complexes in the reaction mixture). IC_{50 complex No. 5} = 12.4 μmol.l^-1 and IC_{50 complex No. 6} = 6.3 μmol.l^-1 for human CYP2D6 were determined. Potential adverse drug interactions could occur in patients taking e. g. antidepressants (amitriptyline, paroxetine) or analgesics (codeine, tramadol) which are known to be metabolized by the CYP2D6 enzyme (2). However, determination of interaction of this copper complexes with another important liver microsomal drug metabolizing CYP should be studied in further experiments in vitro.

Keywords: antimicrobial; compounds; pig; microsomal; CYP2D