Exploring antihypertensive drug leads from Blighia Sapida K. D. Koenig via GC-MS and in silico approaches

Abstract

Globally, hypertension is a leading cause of cardiovascular diseases that account for around 17 million deaths. Despite more studies and management measures, the cause of hypertension is barely unknown, auxiliary antihypertensive medications have some drawbacks which include high prices, adverse effects, and resistivity. The little or no side effects posed by alternative medicines and patient compliance to medicinal plants raised interest in investigating Blighia sapida K. D. Koenig (Ackee) for its bioactive agents including proteins that could be responsible for its antihypertensive properties. Ethanol leave extract was analyzed using gas chromatography-mass spectrometry (GC-MS) analysis to detect the various bioactive compounds, two proteins that play prominent roles in hypertension were studied and retrieved for Molecular Docking using 3D crystal structures, wizard module of Schrödinger Maestro 12.8 employed to prepare the protein. The results of the docking computations were cleaned and analyzed using Excel spreadsheet software. Following receptor and ligand preparation, molecular docking computations were conducted using Glide's ligand docking plugin with extra precision docking to rigorously score ligand-protein interactions. Further graphical representations of the docking results were created using the R Studio package and GraphPad Prism V8.0. Visualization of the molecular interactions of the ligand-protein complexes was conducted. The GC-MS identified a total of 33 compounds in the ethanol extract: Benzenecarboximidothioic acid, N-phenyl-, 4-nitrophenyl ester, N-Serylserine and Palmitic Acid among others. During molecular docking, in-silico pharmacokinetics, and toxicological profiling, serylserine and pirenzepine were identified for their potential interactions with other important proteins related to hypertension including the calcium ion channel and the angiotensin II receptor (ARB). Serylserine and pirenzepine showed potential binding energy against the targeted proteins. This study could produce new antihypertensive medications that are less expensive, more widely available, and less likely to cause adverse effects, thereby meeting public health requirements, particularly in poor nations.