Molecular Dynamics of a N-Cyclohexyl-1,2,4-Oxadiazole Derivative as a Reversible Cruzain Inhibitor in Trypanosoma cruzi

Abstract

Background: Chagas disease kills around 10,000 people yearly, primarily in Latin America, where it is prevalent. Current treatment has limited chronic effectiveness, is unsafe, and has substantial side effects. As a result, the use of oxadiazole derivatives and similar heterocyclic compounds as bioisosteres are well known, and they are prospective candidates in the hunt for novel anti-Trypanosoma cruzi chemicals. Recent research has revealed that the cysteine protease cruzain from T. cruzi is a validated target for disease treatment.

Objective: Thus, using a molecular dynamics simulation, the current study attempted to determine if a significant interaction occurred between the enzyme cruzain and its ligand.

Results: Interactions with the catalytic site and other critical locations were observed. Also, the RMSD values suggested that the molecule under research had stable interactions with its target.

Conclusion: Finally, the findings indicate that the investigated molecule 2b can interfere enzymatic activity of cruzain, indicating that it might be a promising antichagasic drug.

Keywords: Trypanosoma cruzi; chagas disease; computational biology.; molecular docking simulation; molecular dynamics; oxadiazole derivative.