3D-QSAR research of curcumin derivatives

Curcumin exhibits a great ability in various biological and pharmacological activities. Evaluation of curcumin derivatives served to establish the three-dimensional quantitative structure–activity relationship (3D-QSAR) model which was validated by the evaluation of a serial of 22 compounds. Two favorable 3D-QSAR models (CoMFA with q2 = 0.539, R2 = 0.981; CoMSIA with q2 = 0.451, R2 = 0.907) had been developed to predict the biological activity of curcumin derivatives, and external metric qpred2 (CoMFA with 0.79; CoMSIA with 0.78) and rm2(overall) (CoMFA with 0.71; CoMSIA with 0.56) were applied to evaluate the ability of prediction. Comparing the results obtained from both standard models, we found that reducing the carbon chains of curcumin (S2 and A1 zones) could increase its MCF-7 cytotoxicity; exchanging acceptor/donor substituent on A2 and A4, A3 and D3 zones could turnover its cytotoxicity of MCF-7. These results help with understanding the specific activity of curcumin compounds and designing new specific MCF-7 inhibitors.