2. Academic Validation
  3. Discovery of Novel Multiacting Topoisomerase I/II and Histone Deacetylase Inhibitors

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

  • ACS Med Chem Lett. 2015 Jan 14;6(3):239-43. doi: 10.1021/ml500327q.
Shipeng He 1,  Guoqiang Dong 2,  Zhibin Wang 2,  Wei Chen 2,  Yahui Huang 2,  Zhengang Li 2,  Yan Jiang 2,  Na Liu 2,  Jianzhong Yao 2,  Zhenyuan Miao 2,  Wannian Zhang 2,  Chunquan Sheng 3
Affiliations

Affiliations

  • 1 School of Pharmacy, Fujian University of Traditional Chinese Medicine , 1 Qiuyang Road, Fuzhou, Fujian 350122, P. R. China.
  • 2 School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, P. R. China.
  • 3 School of Pharmacy, Fujian University of Traditional Chinese Medicine , 1 Qiuyang Road, Fuzhou, Fujian 350122, P. R. China ; School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, P. R. China.
PMID: 25815139 DOI: 10.1021/ml500327q
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.

Keywords

Evodiamine derivatives; antiproliferative activity; histone deacetylase; topoisomerase I; topoisomerase II.

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