Design, one-pot synthesis, biological profiling, and in silico studies of some heterocycles featuring 4-phenoxy-4-substitutedbenzene-N-acetamide as an α-glucosidase inhibitor

Abstract

Compounds 3a,b, 6a–d, 8a,b, 10a,b, and 13a–f represent novel heterocycles incorporating phenoxyacetamide moieties. These fourteen derivatives were synthesized and screened for α-glucosidase inhibitory activity. Derivatives 6c and 13d exhibited the highest potency, outperforming the reference drug acarbose. Preliminary antioxidant activity, assessed via DPPH assay, identified 6d, 6a, 8a, 13e, and 13f as the most effective, surpassing ascorbic acid. In streptozotocin-induced diabetic mice, compound 6c lowered fasting blood glucose levels, alleviated oxidative stress, and improved hepatic and renal biomarkers, as confirmed by histopathological analysis. Molecular docking studies corroborated these results, demonstrating strong interactions with critical α-glucosidase residues. Overall, these phenoxyacetamide-based heterocycles have emerged as promising scaffolds for developing antidiabetic agents.