Ligand-protein Docking of Gundelia tournefortii and Ocimum basilicum Derivatives in Scanning Hub Protein Targets (PI3K, PDK1, AKT, and RAC1) of the Insulin Signaling Pathway and ADME/Tox Drug Properties

Abstract

Background: Type 2 diabetes is a heterogeneous disease characterized by high blood glucose levels. Its prevalence is increasing as a result of lifestyle, related genes expression, and insufficient insulin signaling. The activation or inhibition of some proteins in the insulin signaling pathway play a vital role in glucose uptake into the cells and in maintaining serum glucose homeostasis. Phosphoinositide-3-kinase (PI3K), 3-phosphoinositide-dependent protein kinase-1 (PDK1), Protein kinase B [PKB, also known as the serine and threonine kinase (AKT)], and Rac family small GTPase 1 (RAC1) are key proteins that play important roles in the liberation of Glucose Transported-4 (GLUT4) vesicle, and consequently the uptake of glucose in response to the insulin signal of hyperglycemia. Objective: In this study, we have focused on the route of targeting insulin signaling proteins for decreasing insulin resistance by targeting the four proteins, PI3K, PDK1, AKT, and RAC1, using in silico studies. Methods: Docking experiments, using AutoDock algorithms, were performed to predict the activity of eight recently purified derivatives of Gundelia tournefortii (GT) and Ocimum basilicum (4-hydroxybenzoic acid, beta-amyrin, beta-sitosterol, chlorogenic acid, lupeol, lupeol-trifluoroacetate, myo-inositol, and stigmasterol) on the insulin signaling proteins. The SwissADME website was used to predict ADMEtox properties for the eight derivatives of the above-mentioned medicinal plants. Results: Most of the Gundelia tournefortii and Ocimum basilicum derivatives have shown variable levels of activation, mainly on the PDK1 and AKT pathways, and to a much lesser extent on the PI3K and RAC1 pathways. Conclusion: The results have indicated that Gundelia tournefortii and Ocimum basilicum derivatives can be potent anti-diabetic drugs, namely in targeting PDK1 and AKT pathways.