Triose Phosphate Isomerase Structure-Based Virtual Screening and In Vitro Biological Activity of Natural Products as Leishmania mexicana Inhibitors

Cutaneous leishmaniasis (CL) is a public health problem affecting more than 98 countries worldwide. No vaccine is available to prevent the disease, and available medical treatments cause serious side effects. Additionally, treatment failure and parasite resistance have made the development of new dr...

Full description

Saved in:
Bibliographic Details
Published in:Pharmaceutics 2023-07, Vol.15 (8), p.2046
Main Authors: González-Morales, Luis D., Moreno-Rodríguez, Adriana, Vázquez-Jiménez, Lenci K., Delgado-Maldonado, Timoteo, Juárez-Saldivar, Alfredo, Ortiz-Pérez, Eyra, Paz-Gonzalez, Alma D., Lara-Ramírez, Edgar E., Yépez-Mulia, Lilian, Meza, Patricia, Rivera, Gildardo
Format: Article
Language:English
Subjects:
Biological activity
Cytotoxicity
Drugs
Enzymes
Leishmania
Ligands
Metabolites
molecular docking
Natural products
Parasites
Parasitic diseases
Penicillin
Pharmacokinetics
Proteins
Protozoa
Simulation
Software
Toxicity
triosephosphate isomerase
virtual screening
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cutaneous leishmaniasis (CL) is a public health problem affecting more than 98 countries worldwide. No vaccine is available to prevent the disease, and available medical treatments cause serious side effects. Additionally, treatment failure and parasite resistance have made the development of new drugs against CL necessary. In this work, a virtual screening of natural products from the BIOFACQUIM and Selleckchem databases was performed using the method of molecular docking at the triosephosphate isomerase (TIM) enzyme interface of Leishmania mexicana (L. mexicana). Finally, the in vitro leishmanicidal activity of selected compounds against two strains of L. mexicana, their cytotoxicity, and selectivity index were determined. The top ten compounds were obtained based on the docking results. Four were selected for further in silico analysis. The ADME-Tox analysis of the selected compounds predicted favorable physicochemical and toxicological properties. Among these four compounds, S-8 (IC50 = 55 µM) demonstrated a two-fold higher activity against the promastigote of both L. mexicana strains than the reference drug glucantime (IC50 = 133 µM). This finding encourages the screening of natural products as new anti-leishmania agents.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics15082046