DESIGN, SYNTHESIS, AND BIOLOGICAL EVALUATION OF THIAZOLE-CARBOXAMIDE DERIVATIVES AS COX INHIBITORS
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Date
2022-12-26
Authors
Rozan Ghassan Sabobeh
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Abstract
ABSTRACT
Non-Steroidal anti-inflammatory drugs (NSAIDs) are often employed to alleviate swelling and discomfort and lower high temperatures. They inhibit the cyclooxygenase enzyme (COX) required to convert arachidonic acid to Prostaglandins that are inflammatory. In this master's thesis, new thiazole derivatives with aniline derivatives were synthesized, specified, and estimated for their selectivity and potency at COX-1 and COX-2 by an in vitro COX inhibition assay kit. The synthesized compounds' cytotoxicity was estimated using an MTS assay against human hepatic stellate (LX-2) and the normal cell line (Hek293T). HRMS, 1H-NMR, and 13C-NMR techniques characterized all newly synthesized chemicals. The results demonstrated that the most effective compound against the COX-1 enzyme was 2b with an IC50 =0.239 µM. It also showed potent activity against COX-2 with IC50=0.191 µM with a selectivity ratio of 1.251. The highest selectivity ratio was (2.766) for 2a compound against COX-2 with an IC50 = 0.958 µM relating to celecoxib ratio (23.8) and its IC50 against COX-2 =0.002 µM. The 2j compound also showed good selectivity towards COX-2 (1.507) with an IC50 of 0.957 µM. All compounds showed negligible cytotoxic activity against the evaluated normal cell lines, and the IC50 values were more than 300 µM, except compound 2b, whose IC50 values were 203.711.89 and 116.96±2.05 µM against LX-2 and Hek293t cell lines, respectively.
Keywords: Anti-inflammatory; Cyclooxygenase enzyme; COX inhibitors; Docking studies; Heterocyclic; Thiazole-carboxamide; NSAIDs.