Pivarcsik Tamás, Tóth Gábor, Szemerédi Nikoletta, Bogdanov Anita, Spengler Gabriella, Kljun Jakob, Kladnik Jerneja, Turel Iztok, Enyedy Éva A
MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Dóm Tér 7, H-6720 Szeged, Hungary.
Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, Dóm Tér 7, H-6720 Szeged, Hungary.
Pharmaceuticals (Basel). 2021 May 27;14(6):518. doi: 10.3390/ph14060518.
In this work, the various biological activities of eight organoruthenium(II) complexes were evaluated to reveal correlations with their stability and reactivity in aqueous media. Complexes with general formula [Ru(η--cymene)(X,Y)(Z)] were prepared, where (X,Y) represents either an ,-ligand (-diketone), ,-ligand (8-hydroxyquinoline) or ,-pyrithione-type ligands (pyrithione = 1-hydroxypyridine-2(1)-thione) with Cl or 1,3,5-triaza-7-phosphaadamantane (PTA) as a co-ligand (Z). The tested complexes inhibit the chlamydial growth on HeLa cells, and one of the complexes inhibits the growth of the human herpes simplex virus-2. The chlorido complexes with ,- and ,-ligands displayed strong antibacterial activity on Gram-positive strains including the resistant (MRSA) and were cytotoxic in adenocarcinoma cell lines. Effect of the structural variation on the biological properties and solution stability was clearly revealed. The decreased bioactivity of the -diketone complexes can be related to their lower stability in solution. In contrast, the ,-pyrithione-type complexes are highly stable in solution and the complexation prevents the oxidation of the ,-ligands. Comparing the binding of PTA and the chlorido co-ligands, it can be concluded that PTA is generally more strongly coordinated to ruthenium, which at the same time decreased the reactivity of complexes with human serum albumin or 1-methylimidazole as well as diminished their bioactivity.
在本研究中，评估了八种有机钌（II）配合物的各种生物活性，以揭示它们在水性介质中的稳定性和反应性之间的相关性。制备了通式为[Ru(η⁶-cymene)(X,Y)(Z)]的配合物，其中(X,Y)代表二齿配体（二酮）、二齿配体（8-羟基喹啉）或吡啶硫酮型配体（吡啶硫酮 = 1-羟基吡啶-2(1)-硫酮），Cl或1,3,5-三氮杂-7-磷杂金刚烷（PTA）作为共配体（Z）。测试的配合物抑制了沙眼衣原体在HeLa细胞上的生长，其中一种配合物抑制了人单纯疱疹病毒2的生长。含有二齿和二齿配体的氯配合物对包括耐甲氧西林金黄色葡萄球菌（MRSA）在内的革兰氏阳性菌株表现出很强的抗菌活性，并且在腺癌细胞系中具有细胞毒性。清楚地揭示了结构变化对生物学性质和溶液稳定性的影响。二酮配合物生物活性的降低可能与其在溶液中的较低稳定性有关。相反，吡啶硫酮型配合物在溶液中高度稳定，并且配位作用阻止了二齿配体的氧化。比较PTA和氯共配体的配位情况，可以得出结论，PTA通常与钌的配位更强，这同时降低了配合物与人血清白蛋白或1-甲基咪唑的反应性，并降低了它们的生物活性。
