Computational Analysis of Plant-Derived Terpenes as α -glucosidase Inhibitors for the Discovery of Therapeutic Agents against Type 2 Diabetes Mellitus

Abstract

The hyperglycemic condition due to diabetes could be managed through retardation of the carbohydrate metabolism by inhibiting the enzymes involved in its degradation. Currently available therapeutic drugs for diabetes as inhibitors of α-glucosidase have limitations on safety, efficacy, and potency. Terpenes have been traditionally used for the treatment of different ailments in humans. Pharmacological activities related to different types of terpenes include antiviral, anticancer, antidepressant, anti-inflammatory, and antidiabetic among others. This study is aimed to unravel the novel antidiabetic plant-derived terpenes as α-glucosidase inhibitors and to investigate the molecular mechanisms underlying this activity. To determine the binding affinity of the plant-derived terpenes with the α-glucosidase target enzyme, an in-house library of 86 terpenes was created after a thorough search of the literature. The terpenes were virtually screened against the receptor protein by performing molecular docking via MOE software package. The binding affinity of the selected compounds was confirmed through molecular dynamic simulation studies. Further, pharmacophore studies, drug-likeness, and ADMET analysis of the top scoring terpenes were also performed. The docking score, drug-likeness assessment, pharmacokinetics analysis, and pharmacophore studies revealed that three compounds namely Gypsogenin -O-α-D-galactopyranosyl-(1-6)-β-D-glucopyranosyl-(1-6)-[β-D-glucopyranosyl-(1-3)]-β-D-glucopyranosyl ester, Segetalic acid and 22-α hydroxychiisanoside are effective inhibitors of α-glucosidase enzyme compared to the standard inhibitors. These findings showed that plant derived terpenes are potential α-glucosidase inhibitors and need to be explored through modern techniques for the development of effective plant-based antidiabetic drugs.