In vitro evaluation of novel mefenamic acid derivatives as potential a-glucosidase and urease inhibitors: Design, synthesis, in silico and cytotoxic studies

Authors：Daud, Saima; Abid, Obaid-ur-Rahman^*; Rehman, Wajid^*; Niaz, Maryam; Sardar, Asma; Rasheed, Liaqat; Niaz, Basit; Shah, Basit Ali; Alotaibi, Hadil Faris; Obaidullah, Ahmad J.; Alanazi, Mohammed M.

Source：Journal of Saudi Chemical Society, 2023, 27(4): 101680.

DOI：10.1016/j.jscs.2023.101680

• Mefenamic acid
• Schiff bases
• Enzyme inhibition
• Cytotoxicity and molecular
• docking studies

This study aim to synthesize new 1,3,4-oxadiazole derivatives incorporating mefenamic acid as promising a-glucosidase and urease inhibitors, potentially leading to the treatment of post-prandial hyperglycemia as well as H. pylori related disorders. In this regards, we have designed a series of Mefenamic acid derivatives. The synthetic compounds were structurally elucidated through 1H NMR, 13C NMR and HR-EIMS analysis. The biological evaluation of these derivatives against a-glucosidase and urease enzyme depicted some novel derivatives with potent inhibition against the said enzymes. All the derivatives exhibited potent inhibition against a-glucosidase enzymes with IC50 rang-ing from 25.81 & PLUSMN; 1.63-113.61 & PLUSMN; 1.31 mM against standard drug acarbose (IC50 = 375.82 & PLUSMN; 1.76 mM) while with respect to urease these derivatives possessed inhibitory potential varied between IC50 = 8.04 & PLUSMN; 1.01-58.18 & PLUSMN; 1.03 mM against the standard thiourea (IC50 = 21.0 & PLUSMN; 1.76 mM). The cell viability results revealed that all of the derivatives were found least cytotoxic. Further-more, molecular docking studies of the most potent derivatives identify number of key features involved in binding interactions between potential inhibitors and the enzyme's active site.& COPY; 2023 The Author(s). Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).