Design, synthesis and in vitro biological evaluation of new coumarin containing oxazole hybrid derivatives as multitarget inhibitor of α-amylase and α-glucosidase for the treatment of diabetes

Sixteen new coumarin-based oxazole derivatives were synthesized and their structures were characterized by employing various spectroscopic tools including HREI-MS and NMR. The in vitro assessment of their α-amylase and α-glucosidase inhibitory activities revealed that that compound 1 (bearing trifluoro methyl at 4-position of aryl ring D) & 16 (having 3-hydroxy & 4-fluoro groups on aryl ring D) exhibited potent α-amylase and α-glucosidase inhibitory potentials with IC50 values of 0.70 ± 0.05 & 0.90 ± 0.05 (against α-amylase) and 1.10 ± 0.10 & 1.20 ± 0.10 (against α-glucosidase) respectively. Analogs 2, 3, 4, 5, 10 and 14 also displayed better inhibitory potentials compared to known potent acarbose inhibitor. Furthermore, the molecular docking studies of the potent analogs docked within the active site cavity of both α-amylase and α-glucosidase showed enhanced binding interaction with good predicted binding affinities. These compounds 1 and 16 could therefore be considered as potentials lead molecules for the development of potentially new improved α-amylase and α-glucosidase inhibitors.