IN SILICO SCREENING OF POTENT PPARGAMMA AGONISTS AMONG NATURAL ANTICANCER COMPOUNDS OF INDIAN ORIGIN

ABSTRACTObjective: Naturally occurring anticancer compounds of Indian origin are well-known for potential therapeutic values. A better understanding ofthe intermolecular interactions of these compounds with peroxisome proliferator-activated receptor gamma (PPARγ) is essential, as its activity isreported in many of the cancers involving colon, breast, gastric, and lung. By this study, it is attempted to perform an in silico screening of naturalanticancer compounds of Indian origin with PPARγ ligand binding domain (LBD). The potential anticancer leads ranked in this study will also exertan additional advantage of PPARγ activity modulation. As PPARγ is also an important nuclear hormone receptor that modulates transcriptionalregulation of lipid and glucose homeostasis and also a key target for many of the anti-diabetic medications, the compounds ranked by this study willalso be utilized for other related therapeutic effects.Methods: This study features in silico screening of compounds from Indian Plant Anticancer compounds database against PPARγ LBD main performedSchrodinger glide virtual screening and docking module to delineate potential PPARγ agonists. Finally, the most potential lead was also subjected tomolecular dynamics simulation to infer the stability of complex formation.Results: The results reveal that majority of the top ranking compounds that interact with LBD was found to be flavonoids, and all these compoundswere found to interact with key residues involved in PPARγ agonist interactions.Conclusion: The leads from this study would be helpful in better understanding of the potential of naturally occurring anticancer compounds ofIndian origin toward targeting PPARγ.Keywords: Peroxisome proliferator-activated receptor-gamma, Agonists, Docking, Natural compounds, Anticancer.Â