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

May 22, 2024Molecular diversity

Chalcone-sulfonyl piperazine compounds as potential diabetes treatments: design, testing, and computer modeling

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Abstract

Compound 5k demonstrated 27-fold greater inhibitory activity against alpha-glucosidase compared to acarbose.

Chalcone-sulfonyl piperazine hybrids were developed to target enzymes associated with diabetes management.
In vitro evaluations indicated that all synthesized compounds showed excellent to good inhibition of alpha-glucosidase and alpha-amylase.
The most effective compound, 5k, had an IC value of 0.31 ± 0.01 µM for alpha-glucosidase and 4.51 ± 1.15 µM for alpha-amylase.
5k exhibited competitive inhibition against alpha-glucosidase according to Lineweaver-Burk analysis.
Cytotoxicity tests showed that all compounds maintained a good safety profile against human fibroblast HT1080 cells.
Molecular docking studies supported the experimental findings regarding the binding interactions of compound 5k with enzyme active sites.

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To address the escalating rates of diabetes mellitus worldwide, there is a growing need for novel compounds. The demand for more affordable and efficient methods of managing diabetes is increasing due to the inevitable side effects associated with existing antidiabetic medications. In this present research, various chalcone-sulfonyl piperazine hybrid compounds (5a-k) were designed and synthesized to develop inhibitors against alpha-glucosidase and alpha-amylase. In addition, several spectroscopic methods, including FT-IR,H-NMR,C-NMR, and HRMS, were employed to confirm the exact structures of the synthesized derivatives. All synthesized 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 (IC = 0.31 ± 0.01 µM) and alpha-amylase (IC = 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 ICvalues 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 potent compound (5k) with the active site of enzymes, molecular docking research was conducted, and the results obtained supported the experimental data. 1 13 50 50 50

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

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