TOWARDS UNDERSTANDING NATURAL ALPHA-GLUCOSIDASE INHIBITORS: A COMPUTATIONAL STUDY

Abstract

Objective: Diabetes mellitus is a metabolic disorder affecting hundreds of millions of people around the world. It is characterized by hyperglycemia caused by impaired glucose homeostasis that results from insufficient insulin production or insulin resistance. There are clinically available α-glucosidase inhibitor drugs that are used to decrease postprandial blood glucose level. However, these drugs have side effects that necessitated the discovery of new α-glucosidase inhibitors with less side effects and high potency. The interest in the use of natural products to deal with diabetes has been increasing. Therefore, the potential of natural α-glucosidase inhibitors to inhibit the enzyme was investigated through computational methods. Material and Method: The binding potential of selected natural α-glucosidase inhibitors was investigated through molecular docking. Thereafter, the stability of the complexes with the highest binding potential were assessed through molecular dynamics (MD) simulation. Result and Discussion: The molecular docking demonstrated that compound 2 had better binding potential than the standard drug, acarbose. Compound 7 had comparable binding potential to the standard drug. Furthermore, all the tested compounds exhibited a reasonable binding potential towards the enzyme but were weaker than the standard drug. The MD simulation demonstrated that compounds 2 and 7 gave complexes with similar stability to the standard drug. The overall computational results revealed that the natural inhibitors investigated had the ability to bind to the enzyme and formed stable complexes. Therefore, these compounds could be potential α-glucosidase inhibitors for clinical use. For this reason, further in vitro investigations on compounds with the highest binding potential is recommended.