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| Synthesis and biological evaluation of 5,6,7-trimethoxy- 1- benzylidene-3,4-dihydro-naphthalen-2-one as tubulinpolymerization inhibitors |
| Jun-Hang Jianga, Can-Hui Zhenga, Chong-Qing Wanga, Juan Wangc, Wei Tiana, Chao Yanga, Yun-Long Songa, Yong Hub, Ju Zhua, You-Yun Zhoua |
a School of Pharmacy, Second Military Medical University, Shanghai 200433, China;
b Department of Neonatology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai 200040, China;
c Shanghai Institute of Pharmaceutical Industry, Shanghai 200437, China |
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Abstract 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.
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Received: 18 January 2015
Published: 27 March 2015
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| Fund: The work was supported by the National Natural Science Foundation of China (Nos. 21172260 and 30901859), Shanghai Natural Science Foundation (No. 09ZR1438800) and "Chen Guang" Project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (No. 12CG42). |
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Corresponding Authors:
Yong Hu, Ju Zhu, You-Yun Zhou
E-mail: huyongcn@163.com;juzhu@smmu.edu.cn;zhouyoujun@smmu.edu.cn
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