2D-QSAR of purine-scaffold novel class of Hsp90 binders that inhibit the proliferation of cancer cells

摘要

The chaperone heat shock protein 90 (Hsp90) is an emerging target for designing anticancer agent due to its important roles in maintaining transformation and modulating the survival and growth potential of cancer cells. Quantitative structure–activity relationship (QSAR) studies have been carried out in a series of purine derivatives with Hsp90 inhibitory activities. The two-diemensional (2D) QSAR studies revealed that the activity is positively influenced by the presence of a halo substituent in the trimethoxyphenyl moiety and by electronic parameter (field effect) of the 9-N substituent where the contribution of the steric parameter (MR) is negative. The best QSAR model with good correlation coefficient (r 2 = 0.738), of high statistical significance (>99.9%) well explained the variance in activity.