Systematic search for benzimidazole compounds and derivatives with antileishmanial effects
Por:
Carlos Sanchez-Salgado, Juan, Bilbao-Ramos, Pablo, Auxiliadora Dea-Ayuela, Maria, Hernandez-Luis, Francisco, Bolas-Fernandez, Francisco, Medina-Franco, Jose L., Rojas-Aguirre, Yareli
Publicada:
1 nov 2018
Resumen:
Leishmaniasis is a neglected tropical disease that currently affects 12
million people, and over 1 billion people are at risk of infection.
Current chemotherapeutic approaches used to treat this disease are
unsatisfactory, and the limitations of these drugs highlight the
necessity to develop treatments with improved efficacy and safety. To
inform the rational design and development of more efficient therapies,
the present study reports a chemoinformatic approach using the ChEMBL
database to retrieve benzimidazole as a target scaffold. Our analysis
revealed that a limited number of studies had investigated the
antileishmanial effects of benzimidazoles. Among this limited number, L.
major was the species most commonly used to evaluate the antileishmanial
effects of these compounds, whereas L. amazonensis and L. braziliensis
were used least often in the reported studies. The antileishmanial
activities of benzimidazole derivatives were notably variable, a fact
that may depend on the substitution pattern of the scaffold. In
addition, we investigated the effects of a benzimidazole derivative on
promastigotes and amastigotes of L. infantum and L. amazonensis using a
novel fluorometric method. Significant antileishmanial effects were
observed on both species, with L. amazonensis being the most sensitive.
To the best of our knowledge, this chemoinformatic analysis represents
the first attempt to determine the relevance of benzimidazole scaffolds
for antileishmanial drug discovery using the ChEMBL database. The
present findings will provide relevant information for future
structure-activity relationship studies and for the investigation of
benzimidazole-derived drugs as potential treatments for leishmaniasis.
Filiaciones:
Carlos Sanchez-Salgado, Juan:
Inst Med Mol & Ciencias Avanzadas, Rayo 11 Jardines del Pedregal, Mexico City 01900, DF, Mexico
Bilbao-Ramos, Pablo:
Univ Complutense Madrid, Fac Farm, Dept Parasitol, Plaza Ramon y Cajal S-N, E-28040 Madrid, Spain
Auxiliadora Dea-Ayuela, Maria:
Univ CEU Cardenal Herrera, Dept Farm, Valencia 46113, Spain
Hernandez-Luis, Francisco:
Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City 04510, DF, Mexico
Bolas-Fernandez, Francisco:
Univ Complutense Madrid, Fac Farm, Dept Parasitol, Plaza Ramon y Cajal S-N, E-28040 Madrid, Spain
Medina-Franco, Jose L.:
Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City 04510, DF, Mexico
Rojas-Aguirre, Yareli:
Univ Nacl Autonoma Mexico, Fac Quim, Dept Farm, Mexico City 04510, DF, Mexico
Univ Nacl Autonoma Mexico, Conacyt, Lab Nacl Manufactura Adit & Tomog Computarizada, Ctr Ciencias Aplicadas & Desarrollo Tecnol, Mexico City 04510, DF, Mexico
Univ Nacl Autonoma Mexico, Inst Invest Mat, Mexico City 04510, DF, Mexico
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