Diabetes mellitus is a chronic metabolic disorder in which the pancreas secretes insulin but the body cells do not recognize it. As a result, carbohydrate metabolism causes hyperglycemia, which may be fatal for various organs. This disease is increasing day by day and it is prevalent among people of all ages, including young adults and children. Acarbose and miglitol are famous alpha-glucosidase inhibitors but they complicate patients with the problems of flatulence, pain, bloating, diarrhea, and loss of appetite. To overcome these challenges, it is crucial to discover new anti-diabetic drugs with minimal side effects. For this purpose, benzotriazinone sulfonamides were synthesized and their structures were characterized by FT-IR, ¹H-NMR and ¹³C-NMR spectroscopy. In vitro alpha-glucosidase inhibition studies of all synthesized hybrids were conducted using the spectrophotometric method. The synthesized compounds revealed moderate-to-good inhibition activity; in particular, nitro derivatives 12e and 12f were found to be the most effective inhibitors against this enzyme, with IC₅₀ values of 32.37 ± 0.15 µM and 37.75 ± 0.11 µM. In silico studies, including molecular docking as well as DFT analysis, also strengthened the experimental findings. Both leading compounds 12e and 12f showed strong hydrogen bonding interactions within the enzyme cavity. DFT studies also reinforced the strong binding interactions of these derivatives with biological molecules due to their lowest chemical hardness values and lowest orbital energy gap values.

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 in vitro experiments. The compounds 14k and 14l 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. In silico study of 14k and 14l was carried out using molecular docking to identify the type of interactions developed between these compounds and enzyme sites. Both potent compounds 14k and 14l 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 14k and 14l towards biological molecules. All computational findings were found to be in good agreement with in vitro results.