Pharmacophore mapping and virtual screening for the identification of new PPARγ agonists

Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S. A. S. Nagar-160 062, Punjab, India Department of Pharmacy, Birla Institute of Technology and Science-Pilani (BITS), Pilani Campus, Vidya Vihar, Pilani-333 031, Rajasthan, India E-mail: pvbharatam@niper.ac.in Manuscript received online 07 July 2020, accepted 20 July 2020 Pharmacophore mapping using a DISCO-based method and virtual screening using molecular docking was employed to identify new leads as anti-hyperglycemic agents for the target PPARϒ. Three pharmacophoric queries were generated, validated, and submitted for virtual screening of commercial databases like NCI, Maybridge, and Lead Quest with a total of 330,989 compounds. The resulting hits were passed through hierarchical virtual filters for data reduction and subsequently docked in the active site of PPARϒ using a FlexX-based docking program. The hits exhibiting better FlexX scores than the reference ligand, rosiglitazone, were analyzed in terms of their binding mode in the active site. This study resulted in the identification of new and interesting structural chemotypes capable of fostering interaction like rosiglitazone in the PPARϒ binding pocket and hence can be further followed for experimental validation