Marloye Mickaël, Inam Haider, Moore Connor J, Debaille Vinciane, Pritchard Justin R, Gelbcke Michel, Meyer Franck, Dufrasne François, Berger Gilles
Microbiology, Bioorganic and Macromolecular Chemistry, Faculté de Pharmacie, Université Libre de Bruxelles (ULB), 1050, Brussels, Belgium.
Department of Biomedical Engineering, Pennsylvania State University, University Park, PA, USA.
J Biol Inorg Chem. 2021 Aug;26(5):535-549. doi: 10.1007/s00775-021-01873-9. Epub 2021 Jun 26.
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.
钌(Ru)和锇(Os)配合物在癌症研究中一直备受关注,可能成为铂类疗法的替代方案。在此,我们详细介绍了三个新的钌和锇配合物系列,并通过物理化学表征进行了支持,包括含时密度泛函理论、水合反应以及金属 - 芳烃键性质的实验与计算相结合的研究。随后对几种癌细胞系评估了细胞毒性概况,不过成效有限。然而,针对活性最高的系列,采用基于RNA干扰的遗传学方法进行了进一步研究,结果表明其可能通过抑制拓扑异构酶II、有丝分裂纺锤体、组蛋白去乙酰化酶(HDAC)和DNA甲基转移酶(DNMT)发挥多靶点作用机制。