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Acridine-Based Antimalarials—From the Very First Synthetic Antimalarial to Recent Developments

Malaria is among the deadliest infectious diseases in the world caused by Plasmodium parasites. Due to the high complexity of the parasite’s life cycle, we partly depend on antimalarial drugs to fight this disease. However, the emergence of resistance, mainly by Plasmodium falciparum, has dethroned...

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Detalles Bibliográficos
Autores principales: Fonte, Mélanie, Tassi, Natália, Gomes, Paula, Teixeira, Cátia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865557/
https://www.ncbi.nlm.nih.gov/pubmed/33498868
http://dx.doi.org/10.3390/molecules26030600
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author Fonte, Mélanie
Tassi, Natália
Gomes, Paula
Teixeira, Cátia
author_facet Fonte, Mélanie
Tassi, Natália
Gomes, Paula
Teixeira, Cátia
author_sort Fonte, Mélanie
collection PubMed
description Malaria is among the deadliest infectious diseases in the world caused by Plasmodium parasites. Due to the high complexity of the parasite’s life cycle, we partly depend on antimalarial drugs to fight this disease. However, the emergence of resistance, mainly by Plasmodium falciparum, has dethroned most of the antimalarials developed to date. Given recent reports of resistance to artemisinin combination therapies, first-line treatment currently recommended by the World Health Organization, in Western Cambodia and across the Greater Mekong sub-region, it seems very likely that artemisinin and its derivatives will follow the same path of other antimalarial drugs. Consequently, novel, safe and efficient antimalarial drugs are urgently needed. One fast and low-cost strategy to accelerate antimalarial development is by recycling classical pharmacophores. Quinacrine, an acridine-based compound and the first clinically tested synthetic antimalarial drug with potent blood schizonticide but serious side effects, has attracted attention due to its broad spectrum of biological activity. In this sense, the present review will focus on efforts made in the last 20 years for the development of more efficient, safer and affordable antimalarial compounds, through recycling the classical quinacrine drug.
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spelling pubmed-78655572021-02-07 Acridine-Based Antimalarials—From the Very First Synthetic Antimalarial to Recent Developments Fonte, Mélanie Tassi, Natália Gomes, Paula Teixeira, Cátia Molecules Review Malaria is among the deadliest infectious diseases in the world caused by Plasmodium parasites. Due to the high complexity of the parasite’s life cycle, we partly depend on antimalarial drugs to fight this disease. However, the emergence of resistance, mainly by Plasmodium falciparum, has dethroned most of the antimalarials developed to date. Given recent reports of resistance to artemisinin combination therapies, first-line treatment currently recommended by the World Health Organization, in Western Cambodia and across the Greater Mekong sub-region, it seems very likely that artemisinin and its derivatives will follow the same path of other antimalarial drugs. Consequently, novel, safe and efficient antimalarial drugs are urgently needed. One fast and low-cost strategy to accelerate antimalarial development is by recycling classical pharmacophores. Quinacrine, an acridine-based compound and the first clinically tested synthetic antimalarial drug with potent blood schizonticide but serious side effects, has attracted attention due to its broad spectrum of biological activity. In this sense, the present review will focus on efforts made in the last 20 years for the development of more efficient, safer and affordable antimalarial compounds, through recycling the classical quinacrine drug. MDPI 2021-01-24 /pmc/articles/PMC7865557/ /pubmed/33498868 http://dx.doi.org/10.3390/molecules26030600 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Fonte, Mélanie
Tassi, Natália
Gomes, Paula
Teixeira, Cátia
Acridine-Based Antimalarials—From the Very First Synthetic Antimalarial to Recent Developments
title Acridine-Based Antimalarials—From the Very First Synthetic Antimalarial to Recent Developments
title_full Acridine-Based Antimalarials—From the Very First Synthetic Antimalarial to Recent Developments
title_fullStr Acridine-Based Antimalarials—From the Very First Synthetic Antimalarial to Recent Developments
title_full_unstemmed Acridine-Based Antimalarials—From the Very First Synthetic Antimalarial to Recent Developments
title_short Acridine-Based Antimalarials—From the Very First Synthetic Antimalarial to Recent Developments
title_sort acridine-based antimalarials—from the very first synthetic antimalarial to recent developments
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865557/
https://www.ncbi.nlm.nih.gov/pubmed/33498868
http://dx.doi.org/10.3390/molecules26030600
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