JBIC Journal of Biological Inorganic Chemistry ( IF 2.7 ) Pub Date : 2021-06-26 , DOI: 10.1007/s00775-021-01873-9 Mickaël Marloye 1 , Haider Inam 2 , Connor J Moore 2 , Vinciane Debaille 3 , Justin R Pritchard 2 , Michel Gelbcke 1 , Franck Meyer 1 , François Dufrasne 1 , Gilles Berger 1, 4
|
Ruthenium (Ru) and osmium (Os) complexes are of sustained interest in cancer research and may be alternative to platinum-based therapy. We detail here three new series of ruthenium and osmium complexes, supported by physico-chemical characterizations, including time-dependent density functional theory, a combined experimental and computational study on the aquation reactions and the nature of the metal–arene bond. Cytotoxic profiles were then evaluated on several cancer cell lines although with limited success. Further investigations were, however, performed on the most active series using a genetic approach based on RNA interference and highlighted a potential multi-target mechanism of action through topoisomerase II, mitotic spindle, HDAC and DNMT inhibition.
Graphic abstract
中文翻译：
新型生物素和吗啉功能化钌和锇半夹心配合物的合成、结构和抗癌特性
钌 (Ru) 和锇 (Os) 复合物在癌症研究中一直受到关注，并且可能是铂类疗法的替代品。我们在此详细介绍了三个新系列的钌和锇配合物，这些配合物得到了物理化学表征的支持，包括随时间变化的密度泛函理论、对水合反应和金属-芳烃键性质的联合实验和计算研究。然后在几种癌细胞系上评估了细胞毒性谱，尽管成功率有限。然而，使用基于 RNA 干扰的遗传方法对最活跃的系列进行了进一步研究，并通过拓扑异构酶 II、有丝分裂纺锤体、HDAC 和 DNMT 抑制强调了潜在的多靶点作用机制。
京公网安备 11010802027423号