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Expanding the Antimalarial Drug Arsenal—Now, But How?

The number of available and effective antimalarial drugs is quickly dwindling. This is mainly because a number of drug resistance-associated mutations in malaria parasite genes, such as crt, mdr1, dhfr/dhps, and others, have led to widespread resistance to all known classes of antimalarial compounds...

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Detalles Bibliográficos
Autores principales: Grimberg, Brian T., Mehlotra, Rajeev K.
Formato: Texto
Lenguaje:English
Publicado: MDPI 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102560/
https://www.ncbi.nlm.nih.gov/pubmed/21625331
http://dx.doi.org/10.3390/ph4050681
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author Grimberg, Brian T.
Mehlotra, Rajeev K.
author_facet Grimberg, Brian T.
Mehlotra, Rajeev K.
author_sort Grimberg, Brian T.
collection PubMed
description The number of available and effective antimalarial drugs is quickly dwindling. This is mainly because a number of drug resistance-associated mutations in malaria parasite genes, such as crt, mdr1, dhfr/dhps, and others, have led to widespread resistance to all known classes of antimalarial compounds. Unfortunately, malaria parasites have started to exhibit some level of resistance in Southeast Asia even to the most recently introduced class of drugs, artemisinins. While there is much need, the antimalarial drug development pipeline remains woefully thin, with little chemical diversity, and there is currently no alternative to the precious artemisinins. It is difficult to predict where the next generation of antimalarial drugs will come from; however, there are six major approaches: (i) re-optimizing the use of existing antimalarials by either replacement/rotation or combination approach; (ii) repurposing drugs that are currently used to treat other infections or diseases; (iii) chemically modifying existing antimalarial compounds; (iv) exploring natural sources; (v) large-scale screening of diverse chemical libraries; and (vi) through parasite genome-based (“targeted”) discoveries. When any newly discovered effective antimalarial treatment is used by the populus, we must maintain constant vigilance for both parasite-specific and human-related factors that are likely to hamper its success. This article is neither comprehensive nor conclusive. Our purpose is to provide an overview of antimalarial drug resistance, associated parasite genetic factors (1. Introduction; 2. Emergence of artemisinin resistance in P. falciparum), and the antimalarial drug development pipeline (3. Overview of the global pipeline of antimalarial drugs), and highlight some examples of the aforementioned approaches to future antimalarial treatment. These approaches can be categorized into “short term” (4. Feasible options for now) and “long term” (5. Next generation of antimalarial treatment— Approaches and candidates). However, these two categories are interrelated, and the approaches in both should be implemented in parallel with focus on developing a successful, long-lasting antimalarial chemotherapy.
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spelling pubmed-31025602011-05-26 Expanding the Antimalarial Drug Arsenal—Now, But How? Grimberg, Brian T. Mehlotra, Rajeev K. Pharmaceuticals (Basel) Review The number of available and effective antimalarial drugs is quickly dwindling. This is mainly because a number of drug resistance-associated mutations in malaria parasite genes, such as crt, mdr1, dhfr/dhps, and others, have led to widespread resistance to all known classes of antimalarial compounds. Unfortunately, malaria parasites have started to exhibit some level of resistance in Southeast Asia even to the most recently introduced class of drugs, artemisinins. While there is much need, the antimalarial drug development pipeline remains woefully thin, with little chemical diversity, and there is currently no alternative to the precious artemisinins. It is difficult to predict where the next generation of antimalarial drugs will come from; however, there are six major approaches: (i) re-optimizing the use of existing antimalarials by either replacement/rotation or combination approach; (ii) repurposing drugs that are currently used to treat other infections or diseases; (iii) chemically modifying existing antimalarial compounds; (iv) exploring natural sources; (v) large-scale screening of diverse chemical libraries; and (vi) through parasite genome-based (“targeted”) discoveries. When any newly discovered effective antimalarial treatment is used by the populus, we must maintain constant vigilance for both parasite-specific and human-related factors that are likely to hamper its success. This article is neither comprehensive nor conclusive. Our purpose is to provide an overview of antimalarial drug resistance, associated parasite genetic factors (1. Introduction; 2. Emergence of artemisinin resistance in P. falciparum), and the antimalarial drug development pipeline (3. Overview of the global pipeline of antimalarial drugs), and highlight some examples of the aforementioned approaches to future antimalarial treatment. These approaches can be categorized into “short term” (4. Feasible options for now) and “long term” (5. Next generation of antimalarial treatment— Approaches and candidates). However, these two categories are interrelated, and the approaches in both should be implemented in parallel with focus on developing a successful, long-lasting antimalarial chemotherapy. MDPI 2011-04-26 /pmc/articles/PMC3102560/ /pubmed/21625331 http://dx.doi.org/10.3390/ph4050681 Text en © 2011 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 license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Review
Grimberg, Brian T.
Mehlotra, Rajeev K.
Expanding the Antimalarial Drug Arsenal—Now, But How?
title Expanding the Antimalarial Drug Arsenal—Now, But How?
title_full Expanding the Antimalarial Drug Arsenal—Now, But How?
title_fullStr Expanding the Antimalarial Drug Arsenal—Now, But How?
title_full_unstemmed Expanding the Antimalarial Drug Arsenal—Now, But How?
title_short Expanding the Antimalarial Drug Arsenal—Now, But How?
title_sort expanding the antimalarial drug arsenal—now, but how?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3102560/
https://www.ncbi.nlm.nih.gov/pubmed/21625331
http://dx.doi.org/10.3390/ph4050681
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