Carbamates of 4&; prime; -demethyl-4-deoxypodophyllotoxin: Synthesis, cytotoxicity and cell cycle effects

In an attempt to generate compounds with superior bioactivity and reduced toxicity, 12 carbamates of 4\'-demethyl-4-deoxypodophyllotoxin, N-(1-oxyl-4\'-demethyl- 4-deoxypodophyllic)-I+/--amino acids amides, were synthesized and evaluated for antiproliferative activity and cell cycle effect...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2011-12, Vol.21 (24), p.7355-7358
Main Authors: Chen, Shi-Wu, Gao, Yuan-Yu, Zhou, Ni-Ni, Liu, Jie, Huang, Wen-Ting, Hui, Ling, Jin, Yan, Jin, Yong-Xin
Format: Article
Language:English
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Summary:In an attempt to generate compounds with superior bioactivity and reduced toxicity, 12 carbamates of 4\'-demethyl-4-deoxypodophyllotoxin, N-(1-oxyl-4\'-demethyl- 4-deoxypodophyllic)-I+/--amino acids amides, were synthesized and evaluated for antiproliferative activity and cell cycle effects. These synthesized compounds proved to be more hydrophilic, as well as improved or comparable in vitro cytotoxicities against four cell lines (A-549, HeLa, SiHa, and HL-60) compared with either parent DPT or anti-cancer drug VP-16. Furthermore, flow cytometric analysis exhibited that N-(1-oxyl-4\'-demethyl-4-deoxypodophyllic)-d-I+/--meth ine amide (15f) induced cell cycle arrest in the G2/M phase in A-549 cells.
ISSN:0960-894X
DOI:10.1016/j.bmcl.2011.10.024