Design, Synthesis and Antitubulin Activity of Novel Podophyllotoxin Derivatives as Potent Anticancer Agent

doi:10.1007/s40242-015-5325-6

Chemical Research in Chinese Universities ›› 2015, Vol. 31 ›› Issue (6): 964-969.doi: 10.1007/s40242-015-5325-6

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Design, Synthesis and Antitubulin Activity of Novel Podophyllotoxin Derivatives as Potent Anticancer Agent

BAI Lifei¹, WANG Renlei¹, ZOU Ye², XU Guohua¹

1. Jiangsu Key Laboratory of Biofunction Molecule, College of Life Science and Cheimistry & Chemical Engineering, Jiangsu Second Normal University, Nanjing 210013, P. R. China;
2. The Third People's Hospital of Zhangjiagang of Jiangsu Province, Zhangjiagang 215611, P. R. China

Received:2015-08-11 Revised:2015-09-22 Online:2015-11-01 Published:2015-10-26
Contact: XU Guohua E-mail:njxgh@hotmail.com
Supported by:
Supported by the National Natural Science Foundation of China(No.21376112), the Natural Science Foundation of the Colleges and Universities in Jiangsu Province, China(No.13KJB350002) and the Natural Science Foundation of the Colleges and Universities Major Project in Jiangsu Province, China(No.15KJA350001).

Abstract

Abstract:

Twenty novel podophyllotoxin derivatives(1―20) were designed and synthesized. The anti-proliferation activities of these compounds were evaluated against three human cancer cell lines(HepG2, Calu-1 and MCF-7) using podophyllotoxin and Combretastatin A4(CA-4) as positive controls. Among all the compounds, compound 2 displayed more significant anti-proliferation activities against MCF-7 and Calu-1 cell lines and showed lower toxicity towards non-cancer cells. Furthermore, the cell cycle and apoptosis analysis results revealed that compound 2 can cause cell arrest at G2/M phase, leading to cancer cell apoptosis. Meanwhile, it can also reduce the adhesive ability of Calu-1 cells to fibronectin and laminin. The docking simulation results demonstrated that compound 10 can nicely bind to the colchicine site of tubulin. The podophyllotoxin derivatives are worthy to be further investigated to obtain more potent anti-cancer drugs.

Key words: Podophyllotoxin, Anticancer, Antitubulin, Cell adhesion

BAI Lifei, WANG Renlei, ZOU Ye, XU Guohua. Design, Synthesis and Antitubulin Activity of Novel Podophyllotoxin Derivatives as Potent Anticancer Agent[J]. Chemical Research in Chinese Universities, 2015, 31(6): 964-969.

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Design, Synthesis and Antitubulin Activity of Novel Podophyllotoxin Derivatives as Potent Anticancer Agent

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