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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8708704 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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