Abstract
Antimicrobial resistance is currently one of the leading causes of death globally, and one of the heaviest health burdens in the African region. Despite this challenge, research and development of novel antimicrobial drugs is still quite slow due to the long process and cost involved. Some of the serious pathogens attributable to antimicrobial-resistant infections are the Extended-spectrum beta-lactamase (ESBL) producing pathogens which mainly include the gram-negative bacteria. The goal of this study was to identify potential ESBL inhibitors from edible millipedes. Millipedes contain a variety of bioactive compounds including alkaloids (p-benzoquinone) and phenols (p-cresol), and they have been used as sources of food for humans. Studies have shown that the Bobo people of Burkina Faso consume three types of millipede species, namely; Tymbodesmus falcatus, Sphenodesmus sheribongensis and Spirostreptidae as food sources. Based on the literature, these edible millipede species contain a variety of compounds in their grandular defensive secretions which include; p-cresol, p-benzoquinone, hydrogen cyanide, toluquinone, 2, 3-dimethoxybenzoquinone, 2-methoxy-3-methylbenzoquinone, toluhydroquinone and mandelonitrile. The aim of this study was therefore to investigate the activity of these compounds secreted by the edible millipede species on ESBL in comparison with 2 positive and 2 negative controls. This work was entirely performed computationally using various bioinformatics tools and softwares and was achieved by performing molecular docking of the ligands (the millipede compounds) against the target protein (ESBL) which served as the receptor. First, the 3D structures of all the ligands were downloaded from the PubChem chemical structures database while that of the target protein (ESBL) was obtained from the RCS Protein Databank (PDB). The structures of both the ligands and the target protein were prepared using UCSF Chimera tool as well as Autodock4 tool and subsequently converted into executable files. Then molecular docking was performed using Autodock vina and the scripts were run on the Windows Command Prompt to determine the binding affinities of the ligands on the target protein, the binding residues, and the physicochemical properties of the ligands as well as the best beta-lactamase enzyme inhibitor. The drug-likeness of the ligands, ADME properties and toxicity were tested using Lipinski’s rule of five, the Swiss Institute of Bioinformatics (Swiss-ADME) software and admetSAR web server, respectively. Out of the eight ligands tested, it was found that 2, 3-dimethoxybenzoquinone with a binding energy of -7.2 is a potential ESBL inhibitor.