In silico screening and identification of leads against multi-targets of type II diabetes in Plectranthus vettiveroides

Abstract

Generally, phytochemicals have activity on multi-targets and such molecules have been used as effective drugs against the diseases caused by multi-factorial causation like diabetes mellitus (DM). Plectranthus vettiveroides (Jacob) N.P. Singh & B.D. Sharma has been used as a polychrest against various diseases including type II diabetes in tradition system of medicine. The present investigation aimed to validate anti-diabetic property of the root derived essential oil of P. vettiveroides and identification of leads with activity on six targets of DM through in silico method. A total of 78 phytochemicals determined through Gas chromatography –mass spectrometry (GC-MS) analysis of the essential oil were docked with each of the six selected targets namely 11β-hydroxysteroid dehydrogenase type 1, dipeptidyl peptidase IV, protein-tyrosine phosphatase 1B, human pancreatic alpha-amylase, human lysosomal acid-alpha-glucosidase, and phosphorylated insulin receptor tyrosine kinase. The structures of the phytochemicals were retrieved from PubChem and the targets were retrieved from Protein Data Bank (PDB). Docking was carried out in AutoDockVina and the molecules with free energy of binding ≤-6 kcal/mol were considered as hit molecule. Out of 78 phytochemicals screened, 39 have activity on all the tested targets. Based on the docking interaction, drug-likeness and absorption, distribution, metabolism, excretion and toxicity (ADMET) property the best lead molecule against each target were determined. The overall results revealed that basically majority of the hits are terpinoides and not induced any toxicity. Therefore, the oil as such can be recommended as medicament against DM, since the individual, synergistic and cumulative effect of phytochemicals may concomitantly inhibit multi-targets of DM and act as an effective drug.