School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Education Mega Centre, No. 280, Waihuandong Road, Guangzhou 510006, PR China.
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, PR China.
J Inorg Biochem. 2021 May;218:111400. doi: 10.1016/j.jinorgbio.2021.111400. Epub 2021 Feb 25.
Recently, rhodium complexes have received intensive attentions due to their tunable chemical and biological properties as well as attractive antitumor activity. In this work, two imidazole triphenylamino rhodium complexes [Rh(ppy)L1]PF6 (Rh1) and [Rh(ppy)L2]PF6 (Rh2) (ppy = 2-phenylpyridine, L1 = 4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)-N,N-diphenylaniline, L2 = N-(4-(1H-imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenyl)-4-methyl-N-(p-tolyl)aniline) have been synthesized and characterized. Both complexes display stronger anticancer activity against a various of cancer cells than cisplatin and they can effectively localize to mitochondria. Further mechanism studies show that Rh1 induce caspase-dependent apoptosis through mitochondrial damage, down-regulate the expression of B-cell lymphoma-2 (Bcl-2)/Bcl2-associated x (Bax) and reactive oxygen species (ROS) elevation. Our work provides a strategy for the construction of highly effective anticancer agents targeting mitochondrial metabolism through rational modification of rhodium complexes.
最近，由于铑配合物具有可调的化学和生物性质以及吸引人的抗肿瘤活性，因此受到了广泛关注。在这项工作中，我们合成并表征了两种咪唑三苯基氨基铑配合物[Rh(ppy)L1]PF6（Rh1）和[Rh(ppy)L2]PF6（Rh2）（ppy=2-苯基吡啶，L1=4-（1H-咪唑并[4,5-f][1,10]菲咯啉-2-基）-N,N-二苯基苯胺，L2=N-（4-（1H-咪唑并[4,5-f][1,10]菲咯啉-2-基）苯基）-4-甲基-N-（对甲苯基）苯胺）。这两种配合物对多种癌细胞的抗癌活性均强于顺铂，并且可以有效地定位于线粒体。进一步的机制研究表明，Rh1 通过线粒体损伤诱导 caspase 依赖性细胞凋亡，下调 B 细胞淋巴瘤-2（Bcl-2）/Bcl2 相关 X（Bax）的表达和活性氧（ROS）的升高。我们的工作为通过合理修饰铑配合物构建针对线粒体代谢的高效抗癌药物提供了一种策略。
