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Synthesis and Biological Evaluation of 7‐Azaisoindigo Derivatives
Author(s) -
Wang ZhaoHui,
Wang Tao,
Yao ShiNing,
Chen Jingcai,
Hua WeiYi,
Yao QiZheng
Publication year - 2010
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200900268
Subject(s) - du145 , chemistry , western blot , cyclin dependent kinase 2 , endogeny , carbon 13 nmr , biological activity , cyclin d1 , stereochemistry , cell culture , elemental analysis , proton nmr , biochemistry , cell cycle , cell , cancer cell , biology , organic chemistry , cancer , in vitro , gene , genetics , lncap
A series of novel 7‐azaisoindigo derivatives 3–14 were designed, synthesized, and structurally characterized by IR, 1 H‐NMR, 13 C‐NMR, mass spectra, and elemental analyses. Their antiproliferative activities were evaluated in a hormone‐independent prostate cancer cell line DU145. Among them, compounds 8 , 9 , 14 showed the highest activities. Our study also showed that compounds 7 , 11 , 12 exhibited higher inhibitory activities on CDK2/cyclin A than that of the positive control meisoindigo. Western blot analysis on DU145 cells treated with compounds 7 and 9 demonstrated that 7‐azaisoindigo derivatives could decrease the level of CDK2 activity (phosphorylation) and the expression of cyclin D1, and increase the expression of endogenous cyclin‐dependent inhibitor p27.