State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, Guangxi, China.
Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, Nanjing, Jiangsu, China.
Dalton Trans. 2021 Aug 21;50(31):10909-10921. doi: 10.1039/d1dt01272j. Epub 2021 Jul 27.
In this study, we proposed to design effective multi-target anticancer agents based on the chelation of nontoxic metals with ligands that possess anticancer activity. In total, five Sn(ii) pyridine-2-carboxaldehyde thiosemicarbazone complexes are synthesized and their activities are tested. Among these complexes, C5 is found to show the highest cytotoxicity on investigating their structure-activity relationships. In addition, C5 not only exhibits an effective inhibitory effect against tumor growth in vivo, but also suppresses angiogenesis and restricts the metastasis of cancer cells in vitro. Multiple mechanisms underlie the antitumor effect of C5, and they include acting against DNA, inducing apoptosis, and inhibiting the activities of anti-apoptotic Bcl-xL protein, metalloproteinase MMP2 and topoisomerase II.
在这项研究中，我们提出了基于将无毒金属与具有抗癌活性的配体螯合来设计有效的多靶抗癌剂。共合成了五个 Sn(ii)吡啶-2-甲醛缩氨硫脲配合物，并测试了它们的活性。在这些配合物中，发现 C5 对其构效关系的研究显示出最高的细胞毒性。此外，C5 不仅在体内显示出对肿瘤生长的有效抑制作用，而且还抑制血管生成并限制癌细胞的转移在体外。C5 的抗肿瘤作用涉及多种机制，包括针对 DNA、诱导细胞凋亡以及抑制抗凋亡 Bcl-xL 蛋白、基质金属蛋白酶 MMP2 和拓扑异构酶 II 的活性。
