In Silico Investigation of Gastroprotective Compounds from n‐Butanol Fraction of Costus igneus on Antiulcer Druggable Targets

Abstract

Gastric ulcer is a common gastrointestinal tract disorder characterized by discontinuation in the stomach mucosal lining and forming a painful lesion. Costus igneus is an ethnobotanical plant used in the management of gastrointestinal disturbances. This study characterized the gastroprotective bioactive compounds from n‐butanol fraction of C. igneus leaf (CIBF) and investigated their druggability effects on selected antiulcer targets using in silico approach.CIBF compounds were identified and characterized using gas chromatography‐mass spectrometry (GC‐MS) method. The 3D structures of CIBF compounds were downloaded in SDF format from Pubchem National Library of Medicine compound database and used as ligands to dock H+K+ATPase receptor (PDB ID: 5YLV), muscarinic receptor (PDB ID: 5ZHP), urease (PDB ID: 6ZJA) and histamine receptor (using Beta‐1‐adrenergic receptor [PDB ID: 2YCW] as a template). The 3D structures of the proteins were downloaded from the Protein Data Bank. Omeprazole, cimetidine and vonoprazan were used as reference drugs. The ligands and target proteins were processed and prepared for docking in pdb formats by using Chimera 1.14 and OpenBabel GUI version 2.3.2a, respectively. Multi‐targeted molecular docking was done using PyRx – Python Prescription 0.8. Physicochemical and pharmacokinetic properties were analyzed using Osiris DataWarrior version 5.5.0. Bioavailability and drug‐likeness analyses were done using the SwissADME web tool.GC‐MS analysis detected 15 suspected bioactive compounds in CIBF. Molecular docking study showed that 10‐11, (6ʹ,7ʹ) naphthoquinono [3.2] paracyclophane (NQP) had the highest ligand binding affinity for H+K+ATPase, muscarinic receptor, urease and histamine receptor when compared with the others 14 compounds, omeprazole, cimetidine and vonoprazan. Physicochemical properties of NQP did not violate the Lipinski, verber and lead likeness rules. Pharmacokinetic predictive analysis indicated that NQP possesses good oral bioavailability, high gastrointestinal absorption, blood‐brain barrier permeability and no inhibitory effect on cytochrome P450s.Findings from this study showed that NQP exhibited substantial inhibitory effects on proton pump, urease activity, muscarinic and histamine receptors. It also showed good physicochemical and pharmacokinetic properties. It is recommended that n‐butanol fraction of C. igneusleaves should be further explored as a potential source of drug lead candidate for the management of gastric ulcer disease.