New acridine-9-carboxamide linked to 1,2,3-triazole- N -phenylacetamide derivatives as potent α-glucosidase inhibitors: design, synthesis, in vitro, and in silico biological evaluations

摘要: α-Glucosidase plays a major role in degradation of carbohydrates to glucose. Therefore, inhibition this enzyme can be useful the treatment carbohydrate-related diseases such as diabetes, cancer, and viral infections. In study, new series acridine-9-carboxamide linked 1,2,3-triazole-N-phenylacetamide derivatives 5a–m were designed, synthesized, evaluated potent α-glucosidase inhibitors. All synthesized compounds showed excellent good inhibitory activity against with IC50 values 80.3 ± 0.9–564.3 ± 7.2 µM comparison standard drug acarbose (IC50 value = 750.0 ± 10.5 μM). Among compounds, most active compound was 3-bromo derivative 5h around 9.3 times more than acarbose. selected for farther biological evaluations. Kinetic study revealed that it is competitive inhibitor α-glucosidase. Docking its regioisomer 5i 4-bromo substituent also carried out site gain an insight into interaction modes rationalized structure–activity relationship between these two compounds. Compound α-amylase no observed Furthermore, vitro cytotoxic assay human normal cancer cell lines HDF MCF-7, respectively, noncytotoxic agent. silico pharmacokinetic toxicity assays performed obtained results compared