ISSN print edition: 0366-6352
ISSN electronic edition: 1336-9075
Registr. No.: MK SR 9/7
Synthesis, evaluation and docking studies of some 4-thiazolone derivatives as effective lipoxygenase inhibitors
Sushant Kumar Shrivastava, Brijesh K. Patel, Prabhash Nath Tripathi, Pavan Srivastava, Piyoosh Sharma, Avanish Tripathi, Ankit Seth, and Manish Kumar Tripathi
Indian Institute of Technology (Banaras Hindu University), Varanasi, India
Abstract: Some promising 4-thiazolone derivatives as lipoxygenase inhibitors were designed, synthesized, characterized and evaluated for anti-inflammatory activity and respective ulcerogenic liabilities. Compounds (1b, 1e, 3b, and 3e) exhibited considerable in vivo anti-inflammatory activity (57.61, 79.35, 75.00, and 79.35%) against carrageenan-induced rat paw edema model, whereas compounds (1e, 3b, and 3e) were found active against the arachidonic acid-induced paw edema model (55.38, 55.38, and 58.46%). The most potent compound (3e) exhibited lesser ulcerogenic liability compared to the standard diclofenac and zileuton. Further, the promising compounds (1e and 3e) were evaluated for in vitro lipoxygenase (LOX; IC50 = 12.98 µM and IC50 = 12.67 µM) and cyclooxygenase (COX) inhibition assay (COX-1; IC50 > 50 µM and, COX-2; IC50 > 50 µM). The enzyme kinetics of compound 3e was evaluated against LOX enzyme and supported by in silico molecular docking and molecular dynamics simulations studies. Overall, the results substantiated that 5-benzylidene-2-phenyl-4-thiazolones are promising pharmacophore for anti-inflammatory activity.
Keywords: 4-Thiazolone ; One-pot multicomponent reaction ; Anti-inflammatory ; Lipoxygenase
Full paper is available at www.springerlink.com.
Chemical Papers 72 (11) 2769–2783 (2018)