Exploring chalcone-sulfonyl piperazine hybrids as anti-diabetes candidates: Design, synthesis, biological evaluation, and molecular docking study

Abstract

Abstract To combat the rising rates of diabetes mellitus over the world, novel compounds are required. The demand for more affordable and efficient methods of managing diabetes is increasing due to the unavoidable side effects associated with the existing antidiabetic medications. In order to develop inhibitors against alpha-glucosidase and alpha-amylase, various chalcone-sulfonyl piperazine hybrid compounds (5a–k) were designed and synthesized in this present research. In addition, several spectroscopic methods, including FT-IR, 1H-NMR, 13C-NMR, and HRMS, were used to confirm the exact structures of the synthesized derivatives. All synthetic compounds were evaluated for their ability to inhibit alpha-glucosidase and alpha-amylase in vitro using acarbose as the reference standard and they showed excellent to good inhibitory potentials. Compound 5k exhibited excellent inhibitory activity against alpha-glucosidase (IC50 = 0.31 ± 0.01 µM) and alpha-amylase (IC50 = 4.51 ± 1.15 µM), which is 27-fold more active against alpha-glucosidase and 7-fold more active against alpha-amylase compared to acarbose, which had IC50 values of 8.62 ± 1.66 µM for alpha-glucosidase and 30.97 ± 2.91 µM for alpha-amylase. It was discovered from the Lineweaver-Burk plot that 5k exhibited competitive inhibition against alpha-glucosidase. Furthermore, cytotoxicity screening assay results against human fibroblast HT1080 cells showed that all compounds had a good level of safety profile. To explore the binding interactions of the most active compound (5k) with the active site of enzymes, molecular docking research was also conducted, and the results obtained supported the experimental data.