Synthesis and Potential Antidiabetic Properties of Curcumin-Based Derivatives: An In Vitro and In Silico Study of α-Glucosidase and α-Amylase Inhibition

Background: Over the past twenty years, the prevalence of diabetes as one of the most common metabolic diseases has become a public health problem worldwide. Blood glucose control is important in delaying the onset and progression of diabetes-related complications. α-Glycosidase (α- Glu) and α-amylase (α-Amy) are important enzymes in glucose metabolism. Diabetic control through the inhibition of carbohydrate hydrolyzing enzymes is established as an effective strategy. Methods: In this study, curcumin-based benzaldehyde derivatives with high stability, bioavailability, and favorable efficiency were synthesized. Results: The results showed that L13, L8, and L11 derivatives have the highest inhibitory effect on α-Glu with IC50 values of 18.65, 20.6, and 31.7 μM and, also L11, L13, and L8 derivatives have the highest inhibitory effect on α-Amy with IC50 value of 14.8, 21.8, and 44.9 μM respectively. Furthermore, enzyme inhibitory kinetic characterization was also performed to understand the mechanism of enzyme inhibition. Conclusion: L13, compared to the other compounds, exhibited acceptable inhibitory activity against both enzymes. The L13 derivative could be an appropriate candidate for further study through the rational drug design to the exploration of a new class of powerful anti-diabetic drugs considering the antioxidant properties of the synthesized compounds. The derivative helps reduce the glycemic index and limits the activity of the major reactive oxygen species (ROS) producing pathways.