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Discovery of novel multiacting topoisomerase I/II and histone deacetylase inhibitors

ACS Medicinal Chemistry Letters, ISSN: 1948-5875, Vol: 6, Issue: 3, Page: 239-243
2015
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Article Description

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.

Bibliographic Details

He, Shipeng; Dong, Guoqiang; Wang, Zhibin; Chen, Wei; Huang, Yahui; Li, Zhengang; Jiang, Yan; Liu, Na; Yao, Jianzhong; Miao, Zhenyuan; Zhang, Wannian; Sheng, Chunquan

American Chemical Society (ACS)

Biochemistry, Genetics and Molecular Biology; Pharmacology, Toxicology and Pharmaceutics; Chemistry

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