Department of Biology, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, 1000, Ljubljana, Slovenia.
Department of Biotechnology, University of Rijeka, Radmile Matejčić 2, 51000, Rijeka, Croatia.
ChemMedChem. 2018 Oct 22;13(20):2166-2176. doi: 10.1002/cmdc.201800432. Epub 2018 Sep 12.
A small library of 17 organoruthenium compounds with the general formula [Ru (fcl)(chel)(L)] (in which fcl=face capping ligand, chel=chelating bidentate ligand, and L=monodentate ligand) were screened for inhibitory activity against cholinesterases and glutathione-S-transferases of human and animal origins. Compounds were selected to include different chelating ligands (i.e., N,N-, N,O-, O,O-, S,O-) and monodentate ligands that can modulate the aquation rate of the metal species. Compounds with a labile ruthenium chloride bond that provided rapid aquation were found to inhibit both sets of enzymes in reversible competitive modes and at pharmaceutically relevant concentrations. When applied at concentrations that completely abolish the activity of human acetylcholinesterase, the lead compound [(η -p-cymene)Ru(pyrithionato)Cl] (C1 a) showed no undesirable physiological responses on the neuromuscular system. Finally, C1 a was not cytotoxic against non-transformed cells at pharmaceutically relevant concentrations.
筛选了一个包含 17 种有机钌化合物的小文库，其通式为 [Ru(fcl)(chel)(L)]（其中 fcl=面封配体，chel=螯合双齿配体，L=单齿配体），以研究其对人和动物来源的胆碱酯酶和谷胱甘肽-S-转移酶的抑制活性。选择的化合物包括不同的螯合配体（即 N,N-、N,O-、O,O-、S,O-）和可以调节金属物种水合速率的单齿配体。具有不稳定的氯化钌键的化合物被发现以可逆转的竞争性模式并在药物相关浓度下抑制这两组酶。当以完全抑制人乙酰胆碱酯酶活性的浓度应用时，先导化合物[(η-p-cymene)Ru(pyrithionato)Cl]（C1a）在神经肌肉系统上没有表现出不良的生理反应。最后，C1a 在药物相关浓度下对非转化细胞没有细胞毒性。
