In Vitro Antioxidant Activity and Dual-Target Inhibitory Effects of Dipyridamole on α-Amylase and α-Glucosidase: Molecular Mechanisms and Molecular Dynamics Simulations
Abstract
α-Amylase and α-glucosidase are complementary therapeutic targets in type 2 diabetes; simultaneous inhibition provides a dual-blockade strategy to suppress postprandial hyperglycemia. Dipyridamole, a conventional antiplatelet drug with proven anti-inflammatory, antioxidant, and antiproliferative effects and a favorable safety profile, is a candidate for repurposing. This study assessed in vitro antioxidant activity and inhibitory actions against both enzymes, and employed molecular docking, molecular dynamics simulations to elucidate mechanisms. Dipyridamole showed EC50 values of 589.7 μM (ABTS+·), 652.2 μM (·OH), and 1607.1 μM (DPPH·), and IC50 values of 257.6 μM (α-amylase) and 348.8 μM (α-glucosidase). Molecular docking yielded binding free energies of -6.5 and -6.0 kcal/mol for α-amylase and α-glucosidase, respectively, with binding mediated mainly by hydrogen bonds and hydrophobic interactions. Molecular dynamics simulations revealed that, under the present simulation conditions, both the apo forms of α-amylase and α-glucosidase and their respective dipyridamole complexes exhibited relatively stable dynamical behavior throughout the course of the trajectories. Overall, dipyridamole showed not only moderate free radical scavenging capacity but also inhibitory activity against α-amylase and α-glucosidase, suggesting that this molecule may serve as a promising lead compound for further relevant drug development and functional exploration.
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