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

ABSTRACT: 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.

SUBMITTER: He S

PROVIDER: S-EPMC4360171 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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

He Shipeng S Dong Guoqiang G Wang Zhibin Z Chen Wei W Huang Yahui Y Li Zhengang Z Jiang Yan Y Liu Na N Yao Jianzhong J Miao Zhenyuan Z Zhang Wannian W Sheng Chunquan C

ACS medicinal chemistry letters 20150114 3

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 goo ...[more]

PMID: 25815139

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