Shanghai East Hospital, Shanghai Key Lab of Chemical Assessment and Sustainability, School of Chemical Science and Engineering, Tongji University, 1239 Siping Road, 200092 Shanghai, P. R. China.
Dalton Trans. 2020 Jul 7;49(26):8864-8871. doi: 10.1039/d0dt01877e.
To overcome the acquired resistance and the significant side-effects of the reported drugs, four new ruthenium(ii) complexes with alkynyl (Ru1, Ru2, Ru3, Ru4) were designed and synthesized. Ru1, Ru2, Ru3 and Ru4 were characterized by ESI-MS, 1H NMR, 1H-1H COSY NMR and elemental analysis. Compared with Ru2, Ru3, Ru4 and cisplatin, the anti-tumor experiments in vitro and vivo confirmed that Ru1 could most effectively inhibit tumor growth. In the experiments of safety evaluation in vivo, Ru1 could avoid any detectable side-effects compared with cisplatin. DNA binding experiments and cell cycle experiments showed that Ru1 exhibited the strongest DNA binding ability and interfered with the cell cycle by inserting DNA to inhibit tumor growth. The study demonstrated that Ru1 had the potential to be an exciting new drug candidate for glioblastoma treatment.
为了克服已报道药物的获得性耐药性和显著的副作用，设计并合成了四个带有炔基的新型钌（ii）配合物（Ru1、Ru2、Ru3、Ru4）。Ru1、Ru2、Ru3 和 Ru4 通过 ESI-MS、1H NMR、1H-1H COSY NMR 和元素分析进行了表征。与 Ru2、Ru3、Ru4 和顺铂相比，体外和体内抗肿瘤实验证实 Ru1 能够最有效地抑制肿瘤生长。在体内安全性评价实验中，Ru1 与顺铂相比能够避免任何可检测的副作用。DNA 结合实验和细胞周期实验表明，Ru1 表现出最强的 DNA 结合能力，并通过插入 DNA 来干扰细胞周期，从而抑制肿瘤生长。该研究表明，Ru1 有可能成为治疗神经胶质瘤的一种令人兴奋的新药候选物。
