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Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
Development of a multi-target anticancer Sn(ii) pyridine-2-carboxaldehyde thiosemicarbazone complex
Junmiao Wu1, Tongfu Yang1, Xiaojun Wang1
1State 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. fyang@mailbox.gxnu.edu.cn.
Abstract:
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.
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