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Antimalarial activity of Malaria Box Compounds against Plasmodium falciparum clinical isolates
Malaria remains a major cause of childhood deaths in resource-limited settings. In the absence of an effective vaccine, drugs and other interventions have played very significant roles in combating the scourge of malaria. The recent reports of resistance to artemisinin necessitate the need for new a...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683671/ https://www.ncbi.nlm.nih.gov/pubmed/29128848 http://dx.doi.org/10.1016/j.ijpddr.2017.10.005 |
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author | Chirawurah, Jersley D. Ansah, Felix Nyarko, Prince B. Duodu, Samuel Aniweh, Yaw Awandare, Gordon A. |
author_facet | Chirawurah, Jersley D. Ansah, Felix Nyarko, Prince B. Duodu, Samuel Aniweh, Yaw Awandare, Gordon A. |
author_sort | Chirawurah, Jersley D. |
collection | PubMed |
description | Malaria remains a major cause of childhood deaths in resource-limited settings. In the absence of an effective vaccine, drugs and other interventions have played very significant roles in combating the scourge of malaria. The recent reports of resistance to artemisinin necessitate the need for new antimalarial drugs with novel mechanisms of action. Towards the development of new, affordable and easily accessible antimalarial drugs for endemic regions, the Medicines for Malaria Venture (MMV) assembled a total of 400 active antimalarial compounds called the Malaria Box. The potency and the efficacy of the Malaria Box Compounds have been determined mainly using laboratory strains of P. falciparum. This study investigated the potency of twenty compounds from the Malaria Box against four clinical isolates from Ghana, using optimized in vitro growth inhibitory assays. Seven out of the 20 compounds screened had 50% inhibitory concentration (IC(50)) below 500 nM. The most active among the selected compounds was MMV006087 (average IC(50) of 30.79 nM). Variations in the potency of the Malaria Box Compounds were observed between P. falciparum clinical isolates and Dd2 strain. We also investigated the sensitivity of the clinical isolates to chloroquine and artesunate. The N093 clinical isolate was found to be resistant to chloroquine but showed high sensitivity to artesunate. The results underscore the importance of including clinical isolates with different drug-resistant backgrounds, in addition to laboratory strains, in validating potential compounds during antimalarial compound screening programs. |
format | Online Article Text |
id | pubmed-5683671 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-56836712017-11-20 Antimalarial activity of Malaria Box Compounds against Plasmodium falciparum clinical isolates Chirawurah, Jersley D. Ansah, Felix Nyarko, Prince B. Duodu, Samuel Aniweh, Yaw Awandare, Gordon A. Int J Parasitol Drugs Drug Resist Article Malaria remains a major cause of childhood deaths in resource-limited settings. In the absence of an effective vaccine, drugs and other interventions have played very significant roles in combating the scourge of malaria. The recent reports of resistance to artemisinin necessitate the need for new antimalarial drugs with novel mechanisms of action. Towards the development of new, affordable and easily accessible antimalarial drugs for endemic regions, the Medicines for Malaria Venture (MMV) assembled a total of 400 active antimalarial compounds called the Malaria Box. The potency and the efficacy of the Malaria Box Compounds have been determined mainly using laboratory strains of P. falciparum. This study investigated the potency of twenty compounds from the Malaria Box against four clinical isolates from Ghana, using optimized in vitro growth inhibitory assays. Seven out of the 20 compounds screened had 50% inhibitory concentration (IC(50)) below 500 nM. The most active among the selected compounds was MMV006087 (average IC(50) of 30.79 nM). Variations in the potency of the Malaria Box Compounds were observed between P. falciparum clinical isolates and Dd2 strain. We also investigated the sensitivity of the clinical isolates to chloroquine and artesunate. The N093 clinical isolate was found to be resistant to chloroquine but showed high sensitivity to artesunate. The results underscore the importance of including clinical isolates with different drug-resistant backgrounds, in addition to laboratory strains, in validating potential compounds during antimalarial compound screening programs. Elsevier 2017-10-16 /pmc/articles/PMC5683671/ /pubmed/29128848 http://dx.doi.org/10.1016/j.ijpddr.2017.10.005 Text en © 2017 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chirawurah, Jersley D. Ansah, Felix Nyarko, Prince B. Duodu, Samuel Aniweh, Yaw Awandare, Gordon A. Antimalarial activity of Malaria Box Compounds against Plasmodium falciparum clinical isolates |
title | Antimalarial activity of Malaria Box Compounds against Plasmodium falciparum clinical isolates |
title_full | Antimalarial activity of Malaria Box Compounds against Plasmodium falciparum clinical isolates |
title_fullStr | Antimalarial activity of Malaria Box Compounds against Plasmodium falciparum clinical isolates |
title_full_unstemmed | Antimalarial activity of Malaria Box Compounds against Plasmodium falciparum clinical isolates |
title_short | Antimalarial activity of Malaria Box Compounds against Plasmodium falciparum clinical isolates |
title_sort | antimalarial activity of malaria box compounds against plasmodium falciparum clinical isolates |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683671/ https://www.ncbi.nlm.nih.gov/pubmed/29128848 http://dx.doi.org/10.1016/j.ijpddr.2017.10.005 |
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