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 α-amylase and α-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 α-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 α-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 α-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.

Coumarins as Promising Scaffold for the Treatment of Age-related Diseases - An Overview of the Last Five Years.

Degenerative diseases are becoming more common with increasing life expectancy of the human population. The 20th century faced a progressive demographic change in the industrialized world, followed by identical trends in population aging in Asia, Africa, and Middle and South America. A significant increase in chronic age-dependent disorders will soon cause important challenges for several countries. Age-related pathologies are commonly seen in elderly patients. More than 40% of adults over 60 years old present a combination of risk factors, described as metabolic syndrome, which significantly increases the tendency for developing degenerative diseases, and some types of cancers. Among these, Parkinson's, Alzheimer's and cardiovascular diseases are on the top of the list. The discovery of effective cardio- and neuroprotective alternative therapeutics that decrease or block disease's progression at early stages, is the main goal of research groups working in the field. A wide range of different substituted coumarins, and the pharmacological properties they may display, are trend topics because of their synthetic accessibility, as well as their abundance in plants and other naturally-occurring products. These heterocyclic compounds play an important role in a variety of areas, but stand out in the field of Medicinal Chemistry. This review provides an overview of the last five years about the potential of coumarins as modulators of several physiological mechanisms involved in age-related pathologies.