Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research and Pharmaceutical Research Center, School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, P. R. China.
Dalton Trans. 2020 Jul 21;49(27):9454-9463. doi: 10.1039/d0dt01040e. Epub 2020 Jun 29.
Ru(ii)-polypyridyl complexes have been widely studied and well established for their antitumor properties. Modifications of the coordination environment around the Ru atom through a proper choice of the ligand can lead to different modes of action and result in greatly improved anticancer efficacy. Herein, two Ru(ii)-polypyridyl complexes of curcumin were synthesized and characterized as potential anticancer agents. In vitro tests indicated that complexes 1 and 2 displayed excellent antiproliferative activity against the tested cancer cell lines, especially complex 2, which exhibited superior cytotoxicity compared to curcumin and cisplatin. Further biological evaluations demonstrated that complexes 1 and 2 can cause cell apoptosis via DNA interaction and MEK/ERK signaling pathway, which is the first example of a Ru(ii)-polypyridyl complex inhibiting the MEK/ERK signaling pathway and DNA intercalation. Overall, this work suggests that coordination with bioactive agents may endow Ru(ii)-polypyridyl complexes with improved pharmaceutical properties and synergistic effects for cancer therapy.
钌(II)-多吡啶配合物因其抗肿瘤特性而被广泛研究和充分证实。通过适当选择配体来修饰 Ru 原子周围的配位环境,可以导致不同的作用模式,并导致抗癌功效的大大提高。本文合成并表征了两种姜黄素的 Ru(II)-多吡啶配合物,将其作为潜在的抗癌剂。体外试验表明,配合物 1 和 2 对测试的癌细胞系表现出优异的增殖抑制活性,特别是配合物 2,与姜黄素和顺铂相比,表现出更高的细胞毒性。进一步的生物学评价表明,配合物 1 和 2 可以通过 DNA 相互作用和 MEK/ERK 信号通路诱导细胞凋亡,这是首例 Ru(II)-多吡啶配合物抑制 MEK/ERK 信号通路和 DNA 嵌入的例子。总的来说,这项工作表明与生物活性药物的配位可能赋予 Ru(II)-多吡啶配合物改善的药物性质和协同作用,用于癌症治疗。