3D-QSAR and molecular docking analysis of biphenyl amide derivatives as p38α mitogen-activated protein kinase inhibitors.
The p38α mitogen-activated protein (MAP) kinase plays a vital role in treating many inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, Crohn's disease and psoriasis. Herein, we have performed 3D-QSAR and molecular docking analysis on a novel series of biphenyl amides to design potent p38 MAP kinase inhibitors. This study correlates the p38 MAP kinase inhibitory activities of 80 biphenyl amide derivatives to several stereochemical parameters representing steric, electrostatic, hydrophobic, hydrogen bond donor and acceptor fields. The resulting model from CoMFA and CoMSIA exhibited excellent [Formula: see text] values of 0.979 and 0.942, and [Formula: see text] values of 0.766 and 0.748, respectively. CoMFA predicted [Formula: see text] of 0.987 and CoMSIA predicted [Formula: see text] of 0.761 showed that the predicted values were in good agreement with experimental values. Glide (5.5) program gave the path for binding mode exploration between the inhibitors and p38α MAP kinase. We have accordingly designed novel p38α MAP kinase inhibitors by utilizing LeapFrog and predicted with excellent activity in the developed models.
Department of Pharmacoinformatics, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Punjab, India.
Pravin Sundarao
PS
Ambure
Rahul Prakashchand
RP
Gangwal
Abhay T
AT
Sangamwar
D000577:Amides / Q000737:chemistry*; D001665:Binding Sites; D001713:Biphenyl Compounds / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship
D000577:Amides; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D048308:Mitogen-Activated Protein Kinase 14