No abstract

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.

α-Glucosidase inhibition is considered as an effective strategy for the treatment of diabetes mellitus.Currently, three α-glucosidase inhibitors are being used as drugs; Acarbose, Voglibose and Miglitol. The side effects of these drugs are forcing researchers to search for new and effective molecules. In this research work, novel 1,2,3-benzotriazin-4(3H)-one sulfonamides were synthesized and investigated for their α-glucosidase inhibition activity. TCT: DMF adduct have been utilized for the direct synthesis of targeted sulfonamides. All reactions were performed at room temperature under mild conditions. In-vitro enzyme inhibition studies led us to discover many potent inhibitors demonstrating good to excellent activity. The compound 5c with dimethyl substituent was found to be more potent inhibitor than acarbose with the IC 50 value of 29.75±0.14 μM. Compounds 5a, 5b, 5d, 5e, 5f and 5m showed good inhibition results with IC 50 value 31.97±0.03, 33.24±0.01, 33.76±1.05, 35.98±0.03, 30.87±0.51 and 37.24±0.04 µM respectively. Further structure activity relationship was analyzed by molecular docking studies.

A series of fifteen new 2-[3-(3-chlorophenyl)-5,5-dioxidobenzo[e]pyrazolo[4,3-c][1,2]thiazin-4(2H)-yl]-N 0 -arylmethyleneacetohydrazides (5a-o) were synthesized and screened for their anti-HIV-1 and cytotoxicity activity.Out of fifteen pyrazolobenzothiazine-based hydrazones, thirteen were found to be active inhibitors of HIV with EC 50 values \20 lM. Moreover, the cytotoxicity results showed that most of the compounds were toxic to PBM, CEM and Vero cell lines. This information could be used for structural modifications to acquire good candidates of HIV drugs.