Potential Inhibitory Biomolecular Interactions of Natural Compounds With Different Molecular Targets of Diabetes

Type II diabetes is an endemic disease and is responsible for approximately 90% to 95% of diabetes cases. The pathophysiological distortions are majorly β-cell dysfunction, insulin resistance, and long-term inflammation, which all progressively unsettle the control of blood glucose levels and trigger microvascular and macrovascular complications. The diverse pathological disruptions which patients with type II diabetes mellitus exhibit precipitate the opinion that different antidiabetic agents, administered in combination, might be required to curb this menace and maintain normal blood glucose. To this end, natural compounds were screened to identify small molecular weight compounds with inhibitory effects on protein tyrosine phosphatase 1B (PTP1B), dipeptidyl-peptidase-4 (DPP-4), and α-amylase. From the result, the top 5 anthocyanins with the highest binding affinity are reported herein. Further ADMET profiling showed moderate pharmacokinetic profiles for these compounds as well as insignificant toxicity. Cyanidin 3-(p-coumaroyl)-diglucoside-5-glucoside (−15.272 kcal/mol), cyanidin 3-O-(6ʺ-malonyl-3ʺ-glucosyl-glucoside) (−9.691 kcal/mol), and delphinidin 3,5-O-diglucoside (−12.36 kcal/mol) had the highest binding affinities to PTP1B, DPP-4, and α-amylase, respectively, and can be used in combination to control glucose fluctuations. However, validations must be carried out through further in vitro and in vivo tests.