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

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, 1H-NMR, 13C-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 (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 potent compound (5k) with the active site of enzymes, molecular docking research was conducted, and the results obtained supported the experimental data.

Phytochemical Profile, Antioxidant, Enzyme Inhibition, Acute Toxicity, In Silico Molecular Docking and Dynamic Analysis of Apis Mellifera Propolis as Antidiabetic Supplement.

This study aims to identify the phytochemical profile of Apis mellifera propolis and explore the potential of its anti-diabetic activity through inhibition of α-amylase (α-AE), α-glucosidase(α-GE), as well as novel antidiabetic compounds of propolis. Apis mellifera propolis extract (AMPE) exhibited elevated polyphenol 33.26±0.17 (mg GAE/g) and flavonoid (15.45±0.13 mg RE/g). It also indicated moderate strong antioxidant activity (IC50 793.09±1.94 µg/ml). This study found that AMPE displayed promising α-AE and α-GE inhibition through in vitro study. Based on LC-MS/MS screening, 18 unique AMPE compounds were identified, with majorly belonging to anthraquinone and flavonoid compounds. Furthermore, in silico study determined that 8 compounds of AMPE exhibited strong binding to α-AE that specifically interacted with its catalytic residue of ASP197. Moreover, 2 compounds exhibit potential inhibition of α-GE, by interacting with crucial amino acids of ARG315, ASP352, and ASP69. Finally, we suggested that 2,7-Dihydroxy-1-(p-hydroxybenzyl)-4-methoxy-9,10-dihydrophenanthrene and 3(3-(3,4-Dihydroxybenzyl)-7-hydroxychroman-4-one as novel inhibitors of α-AE and α-GE. Notably, these compounds were initially discovered from Apis mellifera propolis in this study. The molecular dynamic analysis confirmed their stable binding with both enzymes over 100 ns simulations. The in vivo acute toxicity assay reveals AMPE as a practically non-toxic product with an LD50 value of 16,050 mg/kg. Therefore, this propolis may serve as a promising natural product for diabetes mellitus treatment.