Špičáková Alena, Horáčková Zuzana, Kopel Pavel, Anzenbacher Pavel
Department of Pharmacology, Faculty of Medicine, Palacký University Olomouc, Hněvotínská 3, 779 00 Olomouc, Czech Republic.
Laboratory of Growth Regulators, Faculty of Science, Palacký University & Institute of Experimental Botany of the Czech Academy of Sciences, Šlechtitelů 27, 78 371 Olomouc, Czech Republic.
Pharmaceuticals (Basel). 2024 Sep 10;17(9):1194. doi: 10.3390/ph17091194.
Two copper(II) mixed ligand complexes with dicarboxylate bridges were prepared and studied, namely Cu(μ-fu)(pmdien)(HO) (complex No. 5) and Cu(μ-dtdp)(pmdien)(HO) (complex No. 6), where Hfu = fumaric acid, pmdien = pentamethyldiethylenetriamine, and Hdtdp = 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.
制备并研究了两种具有二羧酸桥联的铜（II）混合配体配合物，即Cu(μ-fu)(pmdien)(H₂O)（配合物5号）和Cu(μ-dtdp)(pmdien)(H₂O)（配合物6号），其中Hfu = 富马酸，pmdien = 五甲基二亚乙基三胺，Hdtdp = 3,3'-二硫代二丙酸。铜原子通过三齿pmdien配体和水分子的氧以相同方式配位，它们仅在二羧酸桥联方面有所不同。这项工作专注于研究这些潜在抗菌药物对最重要的人体肝脏药物代谢酶——细胞色素P450（CYP），尤其是其CYP2C8、CYP2C19和CYP3A4形式的活性的抑制作用。所得结果使我们能够估计这些潜在药物与同时服用的、由这些CYP酶代谢的药物发生相互作用的可能性。总之，不能排除与同时使用的药物发生药物相互作用而产生不良反应的可能性，因此，局部应用可能是一种相对安全的方法。
