• Navyashree C Suresh
• Krishnegowda Jayachandra
• Mantelingu K
• Umashankara M

Phospholipases A2 (PLA2) are diverse group of enzymes, their main function involves hydrolysis of membrane phospholipids into arachidonic acid and lysophospholipids. These lipid mediators play critical roles in initiation, maintenance, and modulation of cell proliferation. The elevated intracellular PLA2 activities are closely associated with several inflammation-associated diseases including Diabetic Macular Edema, inflammation and oxidative stress. Therefore PLA2 enzymes are an important target for implicated in various inflammatory diseases. In the present study we report the identification of a potent, pyrazole-based small-molecule 7d as PLA2inhibitors shows significant inhibition and its IC50 value was determined (HSF-PLA2IC50:23µM and NN-PLA2IC50:29µM). In addition to the in-vitro studies we have evaluated the efficacy of 7d, in in-vivo method using mouse paw edema model, here it significantly neutralizes the sPLA2 induced edema in a dose dependent manner. Furthermore, it also reduces the MPO activity as well as suppression of inflammatory cells in edematous tissue. Apart from in-vitro and in-vivo method docking studies on sPLA¬2 enzymes which include HSF-PLA2 -8.4and NN-PLA2-8with 7d confirms the binding interactions. So, in this study we are investigate a novelsPLA¬2 inhibitor and it might be exhibits as a good candidate to treat various inflammatory disease conditions after the several preclinical studies.

Inflammation, Arachidonic acid, Secretory phospholipase A2, Edema and Anti-inflammatory, pyrazole.

"Trisubstituted Pyrazoles As Novel Inhibitor of Human Secretory Phospholipase A2 with Antiinflammatory Activity SAR, and Molecular docking studies", International Journal of Emerging Technologies and Innovative Research (www.jetir.org), ISSN:2349-5162, Vol.10, Issue 6, page no.i362-i393, June-2023, Available :http://www.jetir.org/papers/JETIR2306842.pdf

"Trisubstituted Pyrazoles As Novel Inhibitor of Human Secretory Phospholipase A2 with Antiinflammatory Activity SAR, and Molecular docking studies", International Journal of Emerging Technologies and Innovative Research (www.jetir.org | UGC and issn Approved), ISSN:2349-5162, Vol.10, Issue 6, page no. ppi362-i393, June-2023, Available at : http://www.jetir.org/papers/JETIR2306842.pdf