Perception of the interaction behavior between pepsin and the antimicrobial drug secnidazole with combined experimental spectroscopy and computer-aided techniques

Abstract

Drug-pepsin interaction possibly affects pepsin activity, leads to undesirable shift of its functionality, and likely induces adverse effects in the gastrointestinal tract. The present study aims at exploring the interaction of pepsin with the antiprotozoal/antibacterial drug secnidazole adopting a combination of experimental spectroscopy and computational techniques. For this purpose, different spectroscopic methods including fluorescence, synchronous fluorescence, UV-Visible absorption, and infrared spectroscopy were adopted and coordinated with in silico analysis via molecular docking. The employed synchronized approaches evidenced that; pepsin interacted with secnidazole via static mechanism at stomach pH inferring some consequent conformational changes in the structure of pepsin. Thermodynamic study of drug-pepsin interaction demonstrated that the interaction is spontaneous via van der Waals and hydrogen bonding interaction and the orientation of ligand within pepsin cavity was illustrated by molecular docking. The synchronous fluorescence study proved that tyrosine amino acid residues were involved in the interaction more than tryptophan amino acid residues. Eventually, the combined experimental and molecular docking approaches suggest that secnidazole interacts with pepsin and alter its structure, that finding correlates to gastrointestinal side effects related to secnidazole oral administration.

Keywords: Fluorescence; Infrared spectroscopy; Molecular docking; Pepsin; Secnidazole; UV–Visible absorption.