Identification of Novel and Potent Curcuminoids Inhibitors of Tubulin with Anticancer Activities by 3D-QSAR and Molecular Docking

The three-dimensional quantitative structure-activity relationships (3D-QSAR) for 37 curcumin derivatives were constructed by CoMFA and CoMSIA methods, respectively. The results showed that the cross validated coefficient (q(2)) and non-cross-validated coefficient (R-2) were 0.711, 0.962 in CoMFA model and 0.774, 0.856 in CoMSIA model, respectively, which suggests that two models are robust and have good exterior predictive capabilities. Based on these two models and the binding mode with tubulin, nine novel curcuminoids inhibitors which could exhibit much higher anticancer potency and efficiently occupy the colchicine binding site of tubulin, were designed. We expect that the results in this paper have the potential to facilitate the process of design and to develop new potent curcumin derivatives with stronger anticancer activities.