title: 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.
authors: School of Pharmacy, Fujian University of Traditional Chinese Medicine , 1 Qiuyang Road, Fuzhou, Fujian 350122, P. R. China.
authors: Shipeng
authors: S
authors: He
authors: School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, P. R. China.
authors: Guoqiang
authors: G
authors: Dong
authors: School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, P. R. China.
authors: Zhibin
authors: Z
authors: Wang
authors: School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, P. R. China.
authors: Wei
authors: W
authors: Chen
authors: School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, P. R. China.
authors: Yahui
authors: Y
authors: Huang
authors: School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, P. R. China.
authors: Zhengang
authors: Z
authors: Li
authors: School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, P. R. China.
authors: Yan
authors: Y
authors: Jiang
authors: School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, P. R. China.
authors: Na
authors: N
authors: Liu
authors: School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, P. R. China.
authors: Jianzhong
authors: J
authors: Yao
authors: School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, P. R. China.
authors: Zhenyuan
authors: Z
authors: Miao
authors: School of Pharmacy, Second Military Medical University , 325 Guohe Road, Shanghai 200433, P. R. China.
authors: Wannian
authors: W
authors: Zhang
authors: 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.
authors: Chunquan
authors: C
authors: Sheng
keywords: Evodiamine derivatives; antiproliferative activity; histone deacetylase; topoisomerase I; topoisomerase II