ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

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

E-mail: skshrivastava.phe@itbhu.ac.in

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.

DOI: 10.1007/s11696-018-0520-9

Chemical Papers 72 (11) 2769–2783 (2018)