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Discovery of Novel Multiacting Topoisomerase I/II and Histone Deacetylase Inhibitors

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journal contribution
posted on 12.03.2015, 00:00 by Shipeng He, Guoqiang Dong, Zhibin Wang, Wei Chen, Yahui Huang, Zhengang Li, Yan Jiang, Na Liu, Jianzhong Yao, Zhenyuan Miao, Wannian Zhang, Chunquan Sheng
Designing multitarget drugs remains a significant challenge in current antitumor drug discovery. Because of the synergistic effect between topoisomerase and HDAC inhibitors, the present study reported the first-in-class triple inhibitors of topoisomerase I/II and HDAC. On the basis of 3-amino-10-hydroxylevodiamine and SAHA, a series of hybrid molecules was successfully designed and synthesized. In particular, compound 8c was proven to be a potent inhibitor of topoisomerase I/II and HDAC with good antiproliferative and apoptotic activities. This proof-of-concept study also validated the effectiveness of discovering triple topoisomerase I/II and HDAC inhibitors as novel antitumor agents.