GQSAR, PHARMACOPHORE MAPPING AND MOLECULAR DOCKING STUDIES OF SOME PYRIDAZINONE DERIVATIVES.

Various literatures are reported on the versatility of pyridazinone molecules, an article was selected with reported IC50. 20 compounds (S1-S20) were selected for combined and stepwise in silico studies on pyridazinone moieties in the form of GQSAR, pharmacophore matching and molecular docking studies. These studies revealed important physicochemical properties of pyridazinones responsible for various biological activities. Group based QSAR (GQSAR) on COX-2 was carried out and 2 best models were studied. Pharm Mapper webserver was used for in silico reverse target screening to find out potential therapeutic targets for pyridazinones. The targets identified using in-silico method like Tyrosine phosphatases (PDB ID- 1NWL), Sorbitol dehydrogenase (PDB ID- 1PL6), Cell division protein kinase 2 (PDB ID - 2B54), Mitogen activated protein kinase 14 (PDB ID-2ZB1), Glucocorticoid receptor (PDB ID- 3CLD) were further screened by molecular docking approach to find best target among these. Docking scores and interactions of pyridazinones revealed Mitogen activated protein kinase 14 as its putative target. MAP 14 kinase is already a well known anti- inflammatory mediator receptor protein hence this in silico study and the data generated have proved that the molecules having pyridazinone moiety could be developed as anti-inflammatory lead compounds