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

Abstract

This study aim to synthesize new 1,3,4-oxadiazole derivatives incorporating mefenamic acid as promising α-glucosidase and urease inhibitors, potentially leading to the treatment of postprandial 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 α-glucosidase and urease enzyme depicted some novel derivatives with potent inhibition against the said enzymes. All the derivatives exhibited potent inhibition against α-glucosidase enzymes with IC50 ranging from 25.81 ± 1.63–113.61 ± 1.31 µM against standard drug acarbose (IC50 = 375.82 ± 1.76 µM) while with respect to urease these derivatives possessed inhibitory potential varied between IC50 = 8.04 ± 1.01–58.18 ± 1.03 µM against the standard thiourea (IC50 = 21.0 ± 1.76 µM). The cell viability results revealed that all of the derivatives were found least cytotoxic. Furthermore, 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.

Keywords

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