3D-QSAR Studies on Protein Phosphatase 2A Inhibitors as Anti-cancer Agents

Abstract

The tremendous efforts by researcher indicates that cantharidin, nor cantharidin and their analogues shows anti-cancer activity due to their inhibition of cancer cell lines such as HT29, SW480, MCF-7, A2780, H460, A431, DU145 and L1210. The anti-cancer activities of cantharidin, nor cantharidin and their analogues involve the inhibition of serine/threonine protein phosphatises (PPs) activity. In this study, three-dimensional quantitative structure activity relationship (3D-QSAR) like comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA) were performed on a set of cantharid in and nor cantharidin analogues. According to 3D-QSAR studies, The CoMFA model with steric and electrostatic field exhibited q²=0.547, r²=0.784; CoMSIA model displayed q²=0.560, r²=0.871; with a standard error of estimate (SEE) of 0.3855 and 0.3000 and number of component (NOC) 3 and 4 respectively. The developed validated 3D-QSAR models can be used to design and new anti-cancer derivatives.

Keywords: Cantharidin, protein phosphatase inhibitors, anti-cancer, CoMFA, CoMSIA