Curcumin derivatives as inhibitors of carbohydrate digestive enzymes: kinetic and biophysical studies under simulated physiological conditions
Diabetes mellitus; enzymology; enzyme inhibition; antihyperglycemic
The use of digestive enzyme inhibitors is one of the main alternatives for the treatment of diabetes mellitus. The inhibitory potential of curcumin derivatives (natural product) on the action of enzymes such as α-amylase and α-glucosidase have been reported, making it important to evaluate new compounds. Therefore, eleven compounds derived from curcumin were synthesized and characterized and their action as an α-amylase and α-glucosidase inhibitor was evaluated. The determination of α-amylase activity inhibition was performed using the method for determining reducing sugars with 3,5-dinitrosalicylic acid (DNS), using acarbose (AC) as a positive control. The determination of inhibition of α-glucosidase activity was performed using the method by Tanruean et al. (2019). The use of Tris-HCl buffer with CaCl2 (pH 7) resulted in a higher AC concentration to inhibit 50% of the enzyme activity (IC50), equivalent to 19.12 µM, while in phosphate buffer (pH 7) it obtained if IC50 = 29.8 µM. Furthermore, the increase in temperature during the enzyme and starch incubation time led to lower IC50 values. A screening assay using 120 µM for all compounds was performed in order to verify their potential to inhibit α-amylase. In this assay, only four derivatives showed inhibition greater than 50% and of these, only compound 6 had an inhibitory potential similar to AC. Finally, compounds derived from curcumin show promise in terms of inhibiting α-amylase and α-glucosidase, and therefore, new experiments aimed at understanding the mechanism of inhibition are in the execution phase.