Inhibitory Effect on Hexokinase II by Benzimidazoles and the Insight into Interactions

Abstract

Background: Benzimidazoles are aromatic, heterocyclic organic molecules which exhibit pharmacological potential as anti-inflammatory, antiulcer, anti-hypertensive, anticancer agent, and anthelmintic treatments. The benzimidazoles could inhibit human hexokinase II, which is a critical factor in the glycolysis pathway in humans. Methods: Autodock analyses were performed for the initial docking between human hexokinase II and benzimidazoles. To determine the IC50 values by benzimidazole compounds, hexokinase enzyme assay was executed using continuous colorimetric detection. In addition, the insight into binding interactions was revealed primarily by Gromacs molecular dynamics simulations. Results: We tested the most common benzimidazoles such as Fenbendazole, Albendazole, and Mebendazole on the target enzyme hexokinase II. The Autodock vina showed that the binding affinity values were between -7.9 and -6.1 kcal/mol for all three benzimidazoles. The IC50 values were 0.29, 2.5, and 10 μM for Fenbendazole, Albendazole, and Mebendazole, respectively. Conclusions: Taken altogether, Fenbendazole appears to show most effective inhibition on hexokinase II. This research may give better insight in development of target-specific benzimidazole derivatives as potential anticancer therapeutics.