Background: Diabetes mellitus is a challengeable metabolic disorder that leads to a
group of complications when the HbA1c level is 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
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.
Materials and 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: 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
Conclusion: These results suggest that naturally mimicking synthesized flavanone have antidiabetic
and antioxidant properties, which can aid in the development of drugs towards diabetes management.