MOLECULAR DOCKING AND EVALUATION OF ANTILEISHMANIA IN VITRO ACTIVITY OF A METALLIC RUTENE COMPLEX WITH EPIISOPYLOTURIN AND NITRIC OXIDE

Abstract

Leishmaniasis is a chronic infectious disease caused in humans by the bite of an infected mosquito classified as a sand fly. After infection, Leishmania metacyclic parasites will interact primarily with phagocytic cells that will infect and reach tissues and organs, depending on the Leishmania species and the host's immune and genetic interaction. The L. major has unique characteristics within its genus, which differentiates it from T. brucei and T. cruzi metabolically. In addition to having their own characteristics within their genome, they also have particular organelles such as glucosomes, which function as reservoirs of glycolytic and kinetoplast enzymes. Computational Quantum Chemistry provides data algorithms that allow us locate and decipher transition state in chemical transformations providing us with relevant information about molecular interactions of a biological potential, where quantum results are 95% reliable. The present work aims to perform molecular docking tests and evaluation of in vitro antileishmania activity of a ruthenium metal complex with epiisopiloturin and nitric oxide (Epiruno2). The 3D protein structures of L. major targets were obtained from the Protein Data Bank (PDB) database with codes 1e7w (Pteridine reductase), 5nzg (UDP-glucose Pyrophosphorylase), 5g20 (Glycyl Peptide N-tetradecanoyltransferase), 5c7p (Nucleoside diphosphate kinase), 1ezr (Nucleoside hydrolase), 1lml (Leishmanolysin), 4ef8 (Dihydroorotate Dehydrogenase), 5l42 (Pteridine 3-phasease) sugar Tryparedoxin peroxidase) and 2xe4 (Oligopeptidase B). A 60 x 60 x 60 dot cubic box with 0.35 Å resolution was generated between grid points for any protein target.