Glycolytic Inhibition and Antidiabetic Activity on Synthesized Flavanone Scaffolds with Computer Aided Drug Designing Tools

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Author(s): Natarajan Kiruthiga*, Govindaraj Saravanan, Chellappa Selvinthanuja, Kulandaivel Srinivasan, Thangavel Sivakumar

Journal Name: Letters in Drug Design & Discovery

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Background: Diabetes mellitus is a challengeable metabolic disorder that leads to a group of complications when HbA1c level not maintained. Most of the existing drugs available in the market in long-term use may lead to serious adverse effects. Hence, current research focuses on drug development for the management of diabetes by synthesizing natural mimicking flavonoid analogues.

Objective: This study focused on the synthesis of flavanone derivatives imitating natural flavonoid core and investigated for their antidiabetic and antioxidant activity, which can help in the development of drug discovery targeting diabetic management.

Methods: The novel 2-phenyl-2,3-dihydro-chromen-4-ones were synthesized from 1,3-diphenyl-prop-2-en-1-one derivatives and characterized using UV, IR, 1HNMR, 13CNMR and mass spectroscopic techniques. Drug target site was determined using graph theoretical analysis and screened the characterized title compounds for their in-silico studies by analyzing their physiochemical properties, ADMET studies, and molecular docking analysis. Antidiabetic and free radical scavenging effects were investigated both by in-vitro (alpha-amylase inhibitory assay) and in-vivo models. Streptozotocin (STZ) induced rats were used as in-vivo models.

Results and Discussion: The α-amylase inhibitory assay showed flavanones with hydroxyl substitution HFA1-HFA7 had significant IC50 values. The test compounds (HFA3-HFA7) were investigated for their antidiabetic activity on STZ induced rats at 40 mg/kg. The blood glucose level and antioxidant enzymes were significantly restored by title compounds (HFA5, HFA4, and HFA6) with an electron-donating group such as hydroxyl, methoxy and thiophenyl group on ring B compared to glibenclamide.

Conclusion: These results suggest that naturally mimicking synthesized flavanone have antidiabetic and antioxidant properties, which can aid in the development of drug towards diabetes management.

Keywords: Graph theoretical analysis, molecular docking, alpha-amylase inhibitor, streptozotocin, antioxidant, hypoglycemic effect.

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(E-pub Ahead of Print)
DOI: 10.2174/1570180817999201209204523
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