Plant-derived coumarins: emerging natural scaffolds for antidiabetic drug discovery

Diabetes mellitus is a leading global health problem, with type 2 diabetes being the main type and already very inefficient treatments posing a challenge. Plant-based compounds, especially those that are naturally occurring have become very popular lately and are regarded as major sources of new antidiabetic drugs owing to the diversity of their structures and the fact that they act on multiple targets at the same time. One of these groups of compounds is coumarins, which have proved to be an important class of bioactive substances with considerable antidiabetic properties. The review that we are presenting gives an inclusive report on the occurrence of natural coumarins and their derivatives with antidiabetic activity being reported, along with the discussion of their mechanisms of action that include among others the inhibition of the enzymes that digest carbohydrates, increase of the insulin sensitivity, regulation of the glucose uptake, protection of the pancreatic β-cells and regulation of oxidative stress and inflammation. Also, the structure-activity relationships of coumarin derivatives are discussed to bring out the important functional features that are responsible for the biological activity. Moreover, the latest developments in drug design, molecular docking studies and the therapeutic prospects of coumarin-based antidiabetic agents have been reviewed. Overall, this review has pointed out the plant-based coumarins as being very versatile scaffolds in the development of antidiabetic therapeutics that are both safe and effective with fewer side effects.