Phytochemical Screening and Molecular Targets Binding Ability of Selected Bioactive Compounds in the Fruit Extract of Tetrapleura tetraptera

Abstract

In addition to the highly valued sweet and aromatic fragrance of Tetrapleura tetraptera fruit, it is used in ethnomedicine to treat and manage a wide range of diseased conditions. In this study, the methanol extract of the fruits of Tetrapleura tetraptera was analyzed by Gas Chromatography - Mass Spectrometry (GC-MS). Twenty-six different phytochemical compounds and their percentages have been characterized including: 3,4-Dihydroxyphenyl(2,3-trans-Catechin) (3.10%), 9-Octadecenal (3.96%), hexadecane (3.16%), pinene (4.80%), 1-methyl-4-cyclohexene (7.45%), humulene (3.60%), carbonic acid (3.34%), ferulic acid (4.03%), 5,6-dihydroxy-7-Oglucuronide flavone (22.46%), 2,4-Di-tert-butylphenol (8.08%) and oleic acid (10.99%). Molecular docking was done using the Maestro Schrodinger suite and glide tool which uses a genetic algorithm to optimize the placement of ligands within a receptor binding site, and employs an empirical scoring function to evaluate and rank the binding affinity between a ligand and a receptor. Molecular docking showed that bioactive compounds in the fruit extract; Naringenin and Hesperidin exhibit strong binding affinities to receptors of interest; AMP-activated protein kinase (AMPK) and endothelial nitric oxide synthase (eNOS), which are diabetes and hypertension-related target proteins; facilitating insightful structural assessments and predictive analyses. The interaction network of Naringenin and Metformin with AMPK residues showed that Naringenin exhibits greater interaction stability, stronger binding affinity and lower binding energy compared to Metformin, suggesting a potentially higher interaction with the protein target. The interaction network of Hesperidin and Nitroglycerine with eNOS amino acid residues also showed that Hesperidin forms a greater number of stabilizing interactions with more diverse interaction network compared to Nitroglycerine, indicating a stronger and more stable interaction which may contribute to its stronger binding affinity. These findings present T. tetraptera as a promising reservoir of active pharmaceutical ingredients warranting further exploration for novel therapeutic avenues and gives credence to the use of T. tetraptera in herbal medicine for the treatment of various diseases.