Chemistry Africa | 2021
Computational Modeling of the Activity of Metronidazole against EhGα1 of Entamoeba histolytica Enhanced by its Copper and Zinc Complexes
Abstract
The organism Entamoeba histolytica which infects humans causing diarrhoea and dysentery has been fingered to be responsible for a large number of fatalities all over the world. Metronidazole has been used as a chemotherapeutic agent in the inhibition of the activity of this parasite in the human system. In this study, the enhancement of the activity of metronidazole by its copper and zinc complexes against EhGα1 of E. histolytica (PDB ID: 4FID) and their mode of interaction with this protein was investigated in silico. Molecular docking studies showed that the binding affinity of the zinc complex of the drug (–\u20098.2 kcal/mol) was higher than those of the copper complex (–\u20096.5 kcal/mol) and uncomplexed drug (–\u20096.2 kcal/mol). Noncovalent interactions in drug-receptor complexes bring about pharmacological effects at a given protein target. The hydroxyl, nitro and azomethine functional groups were all involved in the interaction of metronidazole with the amino acids in EhGα1 of E. histolytica. The two metronidazole units in the copper and zinc complexes participated in the binding interactions which increased their binding affinity to the protein target. In the metronidazole-copper complex, only the ligands were involved in the protein interactions. The protein–ligand binding action in the metronidazole-zinc complex involved the ligands and coordinating zinc metal. The additional metal ion interaction in this complex enhanced its affinity to the protein thereby impacting greater stability of this drug complex at the binding site. Since zinc is an essential nutrient in the human system, its complex with metronidazole can therefore be used to elicit a better drug action than metronidazole against E. histolytica.