Citation: Jun-Hang Jiang, Can-Hui Zheng, Chong-Qing Wang, Juan Wang, Wei Tian, Chao Yang, Yun-Long Song, Yong Hu, Ju Zhu, You-Yun Zhou. Synthesis and biological evaluation of 5,6,7-trimethoxy- 1- benzylidene-3,4-dihydro-naphthalen-2-one as tubulinpolymerization inhibitors[J]. Chinese Chemical Letters, ;2015, 26(5): 607-609. doi: 10.1016/j.cclet.2015.03.022 shu

Synthesis and biological evaluation of 5,6,7-trimethoxy- 1- benzylidene-3,4-dihydro-naphthalen-2-one as tubulinpolymerization inhibitors

Jun-Hang Jiang ^a ,
Can-Hui Zheng ^a ,
Chong-Qing Wang ^a ,
Juan Wang ^c ,
Wei Tian ^a ,
Chao Yang ^a ,
Yun-Long Song ^a ,
Yong Hu ^b,, ,
Ju Zhu ^a,, ,
You-Yun Zhou ^a,,

1.
a School of Pharmacy, Second Military Medical University, Shanghai 200433, China;
2.
b Department of Neonatology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai 200040, China;
3.
c Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China

Corresponding author: Yong Hu, Ju Zhu, You-Yun Zhou,
Received Date: 18 January 2015
Available Online: 28 February 2015
Fund Project: "Chen Guang" Project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (No. 12CG42). (No. 09ZR1438800)

A series of new combretastatin-A4 analogs were synthesized, in which a six-membered ring connects the linking bridge and A ring, and their tumor cell growth and tubulin-polymerization inhibitory activity were evaluated. These compounds appear to be potential tubulin-polymerization inhibitors. Compounds 1b with amino substituted on position 3 of B ring conferred optimal bioactivity, higher than that of the lead compound 22b and equivalent to that of CA-4. The binding modes of these compounds to tubulin were obtained by molecular docking, which can explain the structure-activity relationship. The studies presented here provide a new structural type for the development of novel antitumor agents.
- Tubulin polymerization inhibitor,
- Antitumor agent,
- Combretastatin-A4 analog
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