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The Potential of 2-Substituted Quinolines as Antileishmanial Drug Candidates
There is a need for new, cost-effective drugs to treat leishmaniasis. A strategy based on traditional medicine practiced in Bolivia led to the discovery of the 2-substituted quinoline series as a source of molecules with antileishmanial activity and low toxicity. This review documents the developmen...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000572/ https://www.ncbi.nlm.nih.gov/pubmed/35408712 http://dx.doi.org/10.3390/molecules27072313 |
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author | Loiseau, Philippe M. Balaraman, Kaluvu Barratt, Gillian Pomel, Sébastien Durand, Rémy Frézard, Frédéric Figadère, Bruno |
author_facet | Loiseau, Philippe M. Balaraman, Kaluvu Barratt, Gillian Pomel, Sébastien Durand, Rémy Frézard, Frédéric Figadère, Bruno |
author_sort | Loiseau, Philippe M. |
collection | PubMed |
description | There is a need for new, cost-effective drugs to treat leishmaniasis. A strategy based on traditional medicine practiced in Bolivia led to the discovery of the 2-substituted quinoline series as a source of molecules with antileishmanial activity and low toxicity. This review documents the development of the series from the first isolated natural compounds through several hundred synthetized molecules to an optimized compound exhibiting an in vitro IC(50) value of 0.2 µM against Leishmania donovani, and a selectivity index value of 187, together with in vivo activity on the L. donovani/hamster model. Attempts to establish structure–activity relationships are described, as well as studies that have attempted to determine the mechanism of action. For the latter, it appears that molecules of this series act on multiple targets, possibly including the immune system, which could explain the observed lack of drug resistance after in vitro drug pressure. We also show how nanotechnology strategies could valorize these drugs through adapted formulations and how a mechanistic targeting approach could generate new compounds with increased activity. |
format | Online Article Text |
id | pubmed-9000572 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-90005722022-04-12 The Potential of 2-Substituted Quinolines as Antileishmanial Drug Candidates Loiseau, Philippe M. Balaraman, Kaluvu Barratt, Gillian Pomel, Sébastien Durand, Rémy Frézard, Frédéric Figadère, Bruno Molecules Review There is a need for new, cost-effective drugs to treat leishmaniasis. A strategy based on traditional medicine practiced in Bolivia led to the discovery of the 2-substituted quinoline series as a source of molecules with antileishmanial activity and low toxicity. This review documents the development of the series from the first isolated natural compounds through several hundred synthetized molecules to an optimized compound exhibiting an in vitro IC(50) value of 0.2 µM against Leishmania donovani, and a selectivity index value of 187, together with in vivo activity on the L. donovani/hamster model. Attempts to establish structure–activity relationships are described, as well as studies that have attempted to determine the mechanism of action. For the latter, it appears that molecules of this series act on multiple targets, possibly including the immune system, which could explain the observed lack of drug resistance after in vitro drug pressure. We also show how nanotechnology strategies could valorize these drugs through adapted formulations and how a mechanistic targeting approach could generate new compounds with increased activity. MDPI 2022-04-02 /pmc/articles/PMC9000572/ /pubmed/35408712 http://dx.doi.org/10.3390/molecules27072313 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Loiseau, Philippe M. Balaraman, Kaluvu Barratt, Gillian Pomel, Sébastien Durand, Rémy Frézard, Frédéric Figadère, Bruno The Potential of 2-Substituted Quinolines as Antileishmanial Drug Candidates |
title | The Potential of 2-Substituted Quinolines as Antileishmanial Drug Candidates |
title_full | The Potential of 2-Substituted Quinolines as Antileishmanial Drug Candidates |
title_fullStr | The Potential of 2-Substituted Quinolines as Antileishmanial Drug Candidates |
title_full_unstemmed | The Potential of 2-Substituted Quinolines as Antileishmanial Drug Candidates |
title_short | The Potential of 2-Substituted Quinolines as Antileishmanial Drug Candidates |
title_sort | potential of 2-substituted quinolines as antileishmanial drug candidates |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9000572/ https://www.ncbi.nlm.nih.gov/pubmed/35408712 http://dx.doi.org/10.3390/molecules27072313 |
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