In silico molecular docking and dynamic simulation of antimalarial compounds from Barleria buxifolia root against type III phosphatidylinositol-4-kinase β: Metabolite Profile Analysis Using LC-MS/HRMS

Abstract

Abstract A member of the Acanthaceae family, Barleria buxifolia Linn (B. buxifolia) is a shrub of medium size. It originated on the Indian peninsula. Even though the plant is widely used in traditional medicine to treat malaria, no studies have been conducted on this species for antimalarial activity. Box-Behnken design (BBD) modeling was used to optimize the percentage of extraction from the dried root of B. buxifolia. The study aims to use high-resolution liquid chromatography-mass spectrometry (LC-MS/HRMS) to discover plant-based components in root extracts of B. buxifolia. The observed chromatogram showed the presence of 13 phytoconstituents. For the first time, these phytoconstituents are identified in B. buxifolia roots. These phytoconstituents were assessed for their anti-malarial potential against the malaria targets of phosphatidylinositol-4-kinase III β (protein data bank ID: 4D0L, 4WAE) using AutoDock Vina-PyRx software. The anti-malarial potential was compared to known inhibitors of artemisinin and MMV390048. One compound was identified and compared with the standard artemisinin, which showed the best docking score and was further confirmed through in silico SwissADME, admetSAR web server, LigPlot analysis, and MD simulation, i.e., 1-[2-(benzhydryloxy)ethyl]-4-(3-phenylpropyl)piperazine. This in silico research plays a crucial role in antimalarial drug discovery, and this research will benefit medicinal chemists by enhancing their understanding and utilization of this phytoconstituents for antimalarial activity.