Alpha-glucosidase inhibitory activities of furanoflavonoids isolated from Pongamia pinnata: DFT calculation, molecular modelling and in vitro studies

Alpha-glucosidase inhibitory activities of furanoflavonoids isolated from Pongamia pinnata: DFT calculation, molecular modelling and in vitro studies

Journal:Natural Product Communications Volume 20, Issue 2, WoS (SCIE), Q3
Author: Nguyễn Tấn Khanh - Scientific Management Department, Dong A University

Objective

This study focuses on evaluating the inhibitory activity of pongaglabrone and pongapin, isolated from Pongamia pinnata in our previous research, inhibit α-glucosidase, an enzyme involved in carbohydrate metabolism. Inhibition of α-glucosidase is a key target for controlling type 2 diabetes, making these compounds promising candidates for further research.

Methods

In vitro inhibitory activity assays were conducted to evaluate the effects of pongaglabrone and pongapin on α-glucosidase. Computational approaches, including Density Functional Theory (DFT) calculations, molecular docking, and molecular dynamics simulations, were employed to assess molecular interactions and stability. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of these compounds were also predicted.

Results

Pongapin and pongaglabrone demonstrated inhibitory activity on α-glucosidase, with IC₅₀ values of 116.5 ± 5.02 μg/mL and 137.10 ± 14.67 μg/mL, respectively. Molecular docking revealed binding affinities of 7.564 kcal/mol for pongapin and 7.929 kcal/mol for pongaglabone. Molecular dynamic simulations confirmed that the complexes between the two compounds and α-glucosidase remained stable over a 200 ns simulation period, indicating favorable interactions and potential inhibitory activity. ADMET analysis suggested that while both compounds are absorbable via the digestive tract, they may present toxicity risks.