A new biological prospective for the 2-phenylbenzofurans as inhibitors of α-glucosidase and of the islet amyloid polypeptide formation

In this study, we have investigated a series of hydroxylated 2-phenylbenzofurans compounds for their inhibitory activity against alpha-amylase and alpha-glucosidase activity. Inhibitors of carbohydrate degrading enzymes seem to have an important role as antidiabetic drugs. Diabetes mellitus is a wide-spread metabolic disease characterized by elevated levels of blood glucose. The most common is type 2 diabetes, which can lead to severe complications. Since the aggregates of islet amyloid polypeptide (IAPP) are common in diabetic patients, the effect of compounds to inhibit amyloid fibril formation was also determined. All the compounds assayed showed to be more active against alpha-glucosidase. Compound 16 showed the lowest IC50 value of the series, and it is found to be 167 times more active than acarbose, the reference compound. The enzymatic activity assays showed that compound 16 acts as a mixed-type inhibitor of alpha-glucosidase. Furthermore, compound 16 displayed effective inhibition of IAPP aggregation and it manifested no significant cytotoxicity. To predict the binding of compound 16 to IAPP and alpha-glucosidase protein complexes, molecular docking studies were performed. Altogether, our results support that the 2-phenylbenzofuran derivatives could represent a promising candidate for developing molecules able to modulate multiple targets involved in diabetes mellitus disorder. (C) 2020 Elsevier B.V. All rights reserved.

Automated summary

The study found that hydroxylated 2-phenylbenzofurans compounds exhibited strong inhibitory activity against alpha-glucosidase, with compound 16 showing the best performance. It also effectively inhibited IAPP aggregation without significant cytotoxicity.