Related Experiment Video
Updated: Jun 11, 2025

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
In Vitro Interaction of Binuclear Copper Complexes with Liver Drug-Metabolizing Cytochromes P450
Alena Špičáková1, Zuzana Horáčková2, Pavel Kopel3
1Department of Pharmacology, Faculty of Medicine, Palacký University Olomouc, Hněvotínská 3, 779 00 Olomouc, Czech Republic.
Abstract:
Two copper(II) mixed ligand complexes with dicarboxylate bridges were prepared and studied, namely [Cu2(μ-fu)(pmdien)2(H2O)2](ClO4)2 (complex No. 5) and [Cu2(μ-dtdp)(pmdien)2(H2O)2](ClO4)2 (complex No. 6), where H2fu = fumaric acid, pmdien = N,N,N',N″,N″ pentamethyldiethylenetriamine, and H2dtdp = 3,3'-dithiodipropionic acid. The copper atoms are coordinated in the same mode by the tridentate pmdien ligand and oxygen of water molecules, and they only differ in the dicarboxylate bridge. This work is focused on the study of the inhibitory effect of these potential antimicrobial drugs on the activity of the most important human liver drug-metabolizing enzymes, cytochromes P450 (CYP), especially their forms CYP2C8, CYP2C19, and CYP3A4. The obtained results allow us to estimate the probability of potential drug interactions with simultaneously administrated drugs that are metabolized by these CYP enzymes. In conclusion, the presence of adverse effects due to drug-drug interactions with concomitantly used drugs cannot be excluded, and hence, topical application may be recommended as a relatively safe approach.
Related Concept Videos
Drug Metabolism: Phase I Reactions
Hepatic Drug Excretion: Enterohepatic Cycling
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
Drug Metabolism: Phase II Reactions
Phase II Reactions: Miscellaneous Conjugation Reactions
A key example involves the conjugation of cyanide ions, which impair cellular respiration and alter hemoglobin into non-oxygen-carrying cyanmethemoglobin. To neutralize this threat, a sulfur atom from thiosulphate is transferred to the cyanide ion, catalyzed by the enzyme rhodanese, resulting in an inactive compound called thiocyanate. The production of...
Drug Biotransformation: Overview
Hepatic Drug Clearance: Role of Transporters

