Synthesis and Biological Evaluation of 7‐Azaisoindigo Derivatives

Abstract

A series of novel 7-azaisoindigo derivatives 3-14 were designed, synthesized, and structurally characterized by IR, 1H-NMR, 13C-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.