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Discovery of New Chemical Tools against Leishmania amazonensis via the MMV Pathogen Box

The protozoan parasite Leishmania causes a spectrum of diseases and there are over 1 million infections each year. Current treatments are toxic, expensive, and difficult to administer, and resistance to them is emerging. In this study, we screened the antileishmanial activity of the Pathogen Box com...

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Autores principales: López-Arencibia, Atteneri, Sifaoui, Ines, Reyes-Batlle, María, Bethencourt-Estrella, Carlos J., San Nicolás-Hernández, Desirée, Lorenzo-Morales, Jacob, Piñero, José E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708704/
https://www.ncbi.nlm.nih.gov/pubmed/34959620
http://dx.doi.org/10.3390/ph14121219
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author López-Arencibia, Atteneri
Sifaoui, Ines
Reyes-Batlle, María
Bethencourt-Estrella, Carlos J.
San Nicolás-Hernández, Desirée
Lorenzo-Morales, Jacob
Piñero, José E.
author_facet López-Arencibia, Atteneri
Sifaoui, Ines
Reyes-Batlle, María
Bethencourt-Estrella, Carlos J.
San Nicolás-Hernández, Desirée
Lorenzo-Morales, Jacob
Piñero, José E.
author_sort López-Arencibia, Atteneri
collection PubMed
description The protozoan parasite Leishmania causes a spectrum of diseases and there are over 1 million infections each year. Current treatments are toxic, expensive, and difficult to administer, and resistance to them is emerging. In this study, we screened the antileishmanial activity of the Pathogen Box compounds from the Medicine for Malaria Venture against Leishmania amazonensis, and compared their structures and cytotoxicity. The compounds MMV676388 (3), MMV690103 (5), MMV022029 (7), MMV022478 (9) and MMV021013 (10) exerted a significant dose-dependent inhibition effect on the proliferation of L. amazonensis promastigotes and intracellular amastigotes. Moreover, studies on the mechanism of cell death showed that compounds 3 and 5 induced an apoptotic process while the compounds 7, 9 and 10 seem to induce an autophagic mechanism. The present findings underline the potential of these five molecules as novel therapeutic leishmanicidal agents.
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spelling pubmed-87087042021-12-25 Discovery of New Chemical Tools against Leishmania amazonensis via the MMV Pathogen Box López-Arencibia, Atteneri Sifaoui, Ines Reyes-Batlle, María Bethencourt-Estrella, Carlos J. San Nicolás-Hernández, Desirée Lorenzo-Morales, Jacob Piñero, José E. Pharmaceuticals (Basel) Article The protozoan parasite Leishmania causes a spectrum of diseases and there are over 1 million infections each year. Current treatments are toxic, expensive, and difficult to administer, and resistance to them is emerging. In this study, we screened the antileishmanial activity of the Pathogen Box compounds from the Medicine for Malaria Venture against Leishmania amazonensis, and compared their structures and cytotoxicity. The compounds MMV676388 (3), MMV690103 (5), MMV022029 (7), MMV022478 (9) and MMV021013 (10) exerted a significant dose-dependent inhibition effect on the proliferation of L. amazonensis promastigotes and intracellular amastigotes. Moreover, studies on the mechanism of cell death showed that compounds 3 and 5 induced an apoptotic process while the compounds 7, 9 and 10 seem to induce an autophagic mechanism. The present findings underline the potential of these five molecules as novel therapeutic leishmanicidal agents. MDPI 2021-11-24 /pmc/articles/PMC8708704/ /pubmed/34959620 http://dx.doi.org/10.3390/ph14121219 Text en © 2021 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 Article
López-Arencibia, Atteneri
Sifaoui, Ines
Reyes-Batlle, María
Bethencourt-Estrella, Carlos J.
San Nicolás-Hernández, Desirée
Lorenzo-Morales, Jacob
Piñero, José E.
Discovery of New Chemical Tools against Leishmania amazonensis via the MMV Pathogen Box
title Discovery of New Chemical Tools against Leishmania amazonensis via the MMV Pathogen Box
title_full Discovery of New Chemical Tools against Leishmania amazonensis via the MMV Pathogen Box
title_fullStr Discovery of New Chemical Tools against Leishmania amazonensis via the MMV Pathogen Box
title_full_unstemmed Discovery of New Chemical Tools against Leishmania amazonensis via the MMV Pathogen Box
title_short Discovery of New Chemical Tools against Leishmania amazonensis via the MMV Pathogen Box
title_sort discovery of new chemical tools against leishmania amazonensis via the mmv pathogen box
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8708704/
https://www.ncbi.nlm.nih.gov/pubmed/34959620
http://dx.doi.org/10.3390/ph14121219
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