A small library of 17 organoruthenium compounds with the general formula [Ru^II(fcl)(chel)(L)]ⁿ⁺ (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 [(η⁶‐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.

中文翻译：

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有机钌前药是新型的胆碱酯酶和谷胱甘肽-S-转移酶抑制剂

筛选了17个具有通式[Ru ^II（fcl）（chel）（L）] ^{n +的}有机钌化合物的小型文库（其中fcl =面帽配体，chel =螯合双齿配体和L =单齿配体）用于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‐）和单齿配体可以调节金属物质的水合速率。发现提供快速水合的具有不稳定的氯化钌键的化合物以可逆的竞争方式和药学上相关的浓度抑制两组酶。当其浓度完全消除人乙酰胆碱酯酶的活性施加时，铅化合物[（η ⁶ - p -cymene）的Ru（pyrithionato）CL]（C1一）显示神经肌肉系统上没有不期望的生理反应。最后，C1一个不反对在药物相关浓度的非转化的细胞的细胞毒性。