An In Silico Molecular Docking and ADMET Studies of Some GC-MS Analysed Compounds from Methanol Extract of Mitracapus hirtus

Abstract

Introduction: Fungal infections, particularly in Nigeria, represent a significant public health concern and are among the most prevalent infections in Sub-Saharan Africa. Methods: An in silico molecular docking and ADMET analysis were conducted on several GC-MS-analyzed compounds targeting two fungal enzymes—Squalene Synthase (SS) and Lanosterol-14α Demethylase (14α DM). The analyses were performed using PyRx software’s AutoDock tools, SwissADME, and PROTox II. Results: The docking analysis of seven selected compounds from the GC-MS analysis, including Methyl 3-[(3-chlorophenyl)methyl]-2-cyclohexylimidazo[1,2-a]pyridine-6-carboxylate, 4-(Phenylsulfanyl)-6-(pyrrolidin-1-yl)-2,1,3-benzoxadiazole, 2,4,6-Triphenylthiopyran, 3-(Naphthalen-1-ylmethyl)-1-pentyl-1H-indole, 5-(Benzyloxy)-1-methyl-1H-indole, 1-(2H-1,3-Benzodioxol-5-yl)-3-(7-methoxy-2H-1,3-benzodioxol-5-yl)prop-2-en-1-one, and 2-Benzo[1,3]dioxol-5-yl-8-methoxy-3-nitro-2H-chromene, revealed interactions between the selected ligands and the active sites of SS and 14α DM. The binding scores for the best poses ranged from -8.6 to -10.3 kcal/mol for SS, and from -8.7 to -9.7 kcal/mol for 14α DM. Among these, 2,4,6-Triphenylthiopyran demonstrated the highest affinity and the lowest docking score for both targets, while 5-(Benzyloxy)-1-methyl-1H-indole and 2-Benzo[1,3]dioxol-5-yl-8-methoxy-3-nitro-2H-chromene exhibited the highest docking scores against the respective target enzymes. The drug-likeness parameters and pharmacokinetic properties of the phytochemical constituents of M. hirtus showed molecular weights ranging from 237.30 to 382.88 g/mol, numbers of rotatable bonds from 3 to 6, H-bond donors were 0 for all test compounds, H-bond acceptors ranged from 0 to 6, iLogP values ranged from 2.87 to 4.01, TPSA values ranged from 4.93 to 82.74 Ų, and molar refractivity values ranged from 74.18 to 107.82. High GI absorption, BBB permeability, P-glycoprotein substrates, inhibition of CYP1A2, CYP2C19, and CYP2C9, as well as skin permeability (LogKp), were also evaluated. Conclusion: This study identified several compounds as potential inhibitors of SS and 14α DM demethylase, with superior binding affinity compared to co-crystallized ligands, alongside a favorable ADMET profile.

Keywords: Molecular Docking, ADMET, GC-MS, 14α DM, Secondary metabolites