Design, synthesis and biological assessment of new selective COX-2 inhibitors including methyl sulfonyl moiety.

Design, synthesis and biological assessment of new selective COX-2 inhibitors including methyl sulfonyl moiety. Eur J Med Chem. 2020 Oct 09;:112918 Authors: Sağlık BN, Osmaniye D, Levent S, Çevik UA, Çavuşoğlu BK, Özkay Y, Kaplancıklı ZA Abstract Nonsteroidal anti-inflammatory drugs (NSAIDs) cause peptic lesions in the gastrointestinal mucosa by inhibiting the cyclooxygenase-1 (COX-1) enzyme. Selective COX-2 inhibition causes decreased side effects over current NSAIDs. Therefore, the studies about selective inhibition of COX-2 enzyme are very important for new drug development. The design, synthesis and biological activity evaluation of novel derivatives bearing thiazolylhydrazine-methyl sulfonyl moiety as selective COX-2 inhibitors were aimed in this paper. The structures of synthesized compounds were assigned using different spectroscopic techniques such as 1H NMR, 13C NMR and HRMS. In addition, the estimation of ADME parameters for all compounds was carried out using in silico process. The evaluation of in vitro COX-1/COX-2 enzyme inhibition was applied according to the fluorometric method. According to the enzyme inhibition results, synthesized compounds showed the selectivity against COX-2 enzyme inhibition as expected. Compounds 3a, 3e, 3f, 3g, 3i and 3j demonstrated significant COX-2 inhibition potencies. Among them, compound 3a was found to be the most effective derivative with an IC50 value of 0.140 ± 0.006 μM...
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Tags: Eur J Med Chem Source Type: research