An in silico Study of Benzophenone Derivatives as Potential Non-Competitive Inhibitors of Trypanosoma cruzi and Leishmania Amazonensis Cysteine Proteinases

AUTOR(ES)

Freitas, Poliany G., Castilho, Thiago E., Almeida, Leticia de, Maciel-Rezende, Claudia M., Costa, Luciano T., Viegas Junior, Claudio, Marques, Marcos J., Santos, Marcelo H. dos, Silveira, Nelson J. F. da

FONTE

J. Braz. Chem. Soc.

DATA DE PUBLICAÇÃO

2018-03

RESUMO

This study investigates the mechanisms of interaction between benzophenone derivatives and cruzain and Llacys1 (the protein expressed by cysteine protease gene isoform 1 of L. amazonensis) by homology modelling, docking and molecular dynamics simulation. The results predict that the same binding site in cruzain and Llacys1 is involved in complexes with benzophenone derivatives that cause non-competitive inhibition of the enzymes. The Gln residue is conserved among the enzymes, and is shown to be a key residue in the allosteric site of these cysteine proteases and in the interaction with benzophenone derivatives. The binding free energies highlight that the main energetic term contributing to the cruzain- and Llacys1-benzophenone compound interactions is the van der Waals term. Experimental results showed that benzophenone derivatives are promising potential inhibitors of cysteine proteases. Moreover, we found that two benzophenone derivatives are the most effective inhibitors of cruzain and L. amazonensis cysteine protease.

Documentos Relacionados

• Electrical interference in non-competitive pacemakers
• The effect of swimming on oral health status: competitive versus non-competitive athletes
• Arylfurans as potential Trypanosoma cruzi trypanothione reductase inhibitors
• Efficacy of sertraline against Trypanosoma cruzi: an in vitro and in silico study
• 8-Methoxy-naphtho[2,3-b]thiophen-4,9-quinone, a non-competitive inhibitor of trypanothione reductase