SYNTHESIS AND CHARACTERIZATION OF QUINOXALINES ANALOGUES AS Α-GLUCOSIDASE INHIBITORS

Abstract

Alpha-Glucosidase inhibition is considered as one of the most viable therapeutic approaches to diabetes mellitus (DM). After optimizing reaction conditions, acetic acid catalyzed one-pot facile synthetic strategy was employed to prepare a series of substituted quinoxaline derivatives 51 (a-e), 52 (a-b), 53 (a-d) and 54a in good yields (70-98%). The manufactured complexes were categorized by spectroscopic analyses i.e., FTIR, LR-MS and HR-MS. These structurally vibrant heterocyclic compounds were screened against alpha-glucosidase enzyme and data displayed overall good inhibition by these molecules. All synthesized analogues 51 (a-e), 52 (a-b), 53 (a-d) and 54a were demonstrated potent inhibitory profiles against α-glucosidase enzyme with IC₅₀ values 18.11±0.75 µM to 41.44±0.88 µM as compared to reference acarbose IC₅₀ value 38.25±0.12 µM. Compound 51c demonstrated excellent inhibition against α-glucosidase enzyme with IC₅₀ value 18.11±0.75µM. 4-Methoxyphenyl- substituent at the para position enhances the inhibitory effect of compound and was originate to be the most vigorous compound in contradiction of α-glucosidase enzyme among all the synthesized compounds of quinoxaline analogues 51 (a-e), 52 (a-b), 53 (a-d) and 54a. The inhibitory activity of the potent compounds of the series presumably due to their considerable structure activity relationship predicts that the electron releasing substituents enhance the α-glucosidase inhibition activity of the target enzyme. In silico study exhibited that compounds 51c, 51d, 53a and 54a had crucial binding interaction patterns. Compound 51c demonstrated excellent interactions with α-glucosidase enzyme as score of 5166 and an atomic contact energy (ACE) value of –261.42 kcal/mol. Therefore, the compound 51c was the most potent compound of the four series should be further investigated as lead towards drug designing against diabetes mellitus and work is in progress on these lines.