Abstract

Map kinases control many cellular events from complex programs, such as embryogenesis, cell differentiation, cell proliferation and cell death to short-term changes required for homeostasis and acute hormonal responses. Molecular docking and 3D-QSAR studies were performed on human P38α MAP kinase inhibitors. Docked conformation obtained for each molecule was used as such for 3D-QSAR analysis. Molecules were divided into training and test set randomly. PLS analysis was performed to obtain QSAR models using CoMFA and CoMSIA studies. Derived models showed good statistical reliability that is evident from their q²_loo, r² and r²pred values. Information obtained from the 3D-QSAR helped us in optimization of lead molecule and design of novel potential inhibitors.

Keywords

P38α Mitogen Activated Protein Kinase, Imidazoles, Comparative molecular field analysis, Comparative molecular similarity indices analysis, Docking