@misc{10481/106476,
year = {2025},
month = {8},
url = {https://hdl.handle.net/10481/106476},
abstract = {Background/Objectives: Leishmaniasis is an infectious disease caused by digenetic protozoa of the genus Leishmania, transmitted by infected female sandflies of the Phlebotominae
subfamily. Current treatments are limited, relying on drugs that were not specifically
developed for this disease and are often associated with high toxicity and elevated costs.
Among alternative therapeutic strategies, antifolate compounds have been investigated
due to their ability to inhibit dihydrofolate reductase (DHFR), an enzyme essential for
folate metabolism in the parasite. However, the parasite circumvents DHFR inhibition
through the activity of pteridine reductase-1 (PTR-1), which maintains folate reduction
and ensures parasite survival. In this context, this study aimed to identify potential PTR-1
inhibitors in Leishmania major through in silico approaches. Methods: The methodology
included virtual screening of molecular databases, Tanimoto similarity analysis, pharmacokinetic and toxicological predictions, and biological activity evaluation in silico. The
most promising compounds were further analyzed via molecular docking. Results: The
virtual screening resulted in 474 molecules, of which 4 structures (M601, M692, M700, and
M703) showed high potential as PTR-1 inhibitors in Leishmania major throughout all stages
of the methodology employed, especially in the results of molecular docking where they
exhibited strong binding affinities and significant interactions with key residues of the
target enzymes. Conclusions: This work provides a solid foundation for advancing these
molecules into experimental validation, contributing to the development of safer and more
effective therapeutic alternatives for the treatment of leishmaniasis.},
publisher = {MDPI},
keywords = {Leishmania major},
keywords = {pteridine reductase-1},
keywords = {Virtual screening},
title = {Identification of Potential Pteridin Reductase-1 Inhibitors for the Treatment of Leishmaniasis: A Bioinformatics Approach},
doi = {10.3390/ph18081237},
author = {da S. R. Júnior, Paulo R. and de Lima, Lúcio R. and Silva, Luciane B. and S. Ramos, Ryan and da S. Sanches, Vitor H. and M. Kimani, Njogu and H. G. Trossini, Gustavo and Campos Rosa, Joaquín María and C. Lobato, Cleison and B. R. Santos, Cleydson},
}