Docking and 3D QSAR Studies on p38α MAP Kinase Inhibitors

Abstract

The p38 signaling cascade has emerged as an attractive target for the design of novel chemotherapeutic agents for the treatment of inflammatory diseases. Three dimensional quantitative structure- activity relationship (3D- QSAR) studies were performed on a series of 25, 2-aminothiazole analogs as inhibitors of p38α mitogen activated protein (MAP) kinase. The docking results provided a reliable conformational alignment scheme for the 3D-QSAR model. The 3D-QSAR model showed very good statistical results namely q2, r2and r2predvalues for both comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The CoMFA and CoMSIA models & docking results provided the most significant correlation of steric, electrostatic, hydrophobic,H-bond donor,H-bond acceptor fields with biological activities and the provided values were in good agreement with the experimental results. The information rendered from molecular modeling studies gave valuable clues to optimize the lead and design new potential inhibitors.

Pharmacophore and QSAR Studies to Design Novel Histone Deacetylase 2 Inhibitors

“…The grid point is defaulted with the 0.2 nm grid spacing (50–52). In CoMSIA study, the hydrophobic, hydrogen bond acceptor, and hydrogen bond donor parameters in addition to steric and electrostatic were calculated in case of the CoMSIA fields at each lattice (53).…”