A Combined Experimental and Computational Study of Novel Benzotriazinone Carboxamides as Alpha-Glucosidase Inhibitors

Diabetes is a chronic metabolic disorder of the endocrine system characterized by persistent hyperglycemia appears due to the deficiency or ineffective use of insulin. The glucose level of diabetic patients increases after every meal and medically recommended drugs are used to control hyperglycemia. Alpha-glucosidase inhibitors are used as antidiabetic medicine to delay the hydrolysis of complex carbohydrates. Acarbose, miglitol, and voglibose are commercial drugs but patients suffer side effects of flatulence, bloating, diarrhea, and loss of hunger. To explore a new antidiabetic drug, a series of benzotriazinone carboxamides was synthesized and their alpha-glucosidase inhibition potentials were measured using <i>in vitro</i> experiments. The compounds <b>14k</b> and <b>14l</b> were found to be strong inhibitors compared to the standard drug acarbose with IC₅₀ values of 27.13 ± 0.12 and 32.14 ± 0.11 μM, respectively. <i>In silico</i> study of <b>14k</b> and <b>14l</b> was carried out using molecular docking to identify the type of interactions developed between these compounds and enzyme sites. Both potent compounds <b>14k</b> and <b>14l</b> exhibited effective docking scores by making their interactions with selected amino acid residues. Chemical hardness and orbital energy gap values were investigated using DFT studies and results depicted affinity of <b>14k</b> and <b>14l</b> towards biological molecules. All computational findings were found to be in good agreement with <i>in vitro</i> results.