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Nopol-Based Quinoline Derivatives as Antiplasmodial Agents

Malaria remains a significant cause of morbidity and mortality in Sub-Saharan Africa and South Asia. While clinical antimalarials are efficacious when administered according to local guidelines, resistance to every class of antimalarials is a persistent problem. There is a constant need for new anti...

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Autores principales: Nyamwihura, Rogers J., Zhang, Huaisheng, Collins, Jasmine T., Crown, Olamide, Ogungbe, Ifedayo Victor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917639/
https://www.ncbi.nlm.nih.gov/pubmed/33673007
http://dx.doi.org/10.3390/molecules26041008
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author Nyamwihura, Rogers J.
Zhang, Huaisheng
Collins, Jasmine T.
Crown, Olamide
Ogungbe, Ifedayo Victor
author_facet Nyamwihura, Rogers J.
Zhang, Huaisheng
Collins, Jasmine T.
Crown, Olamide
Ogungbe, Ifedayo Victor
author_sort Nyamwihura, Rogers J.
collection PubMed
description Malaria remains a significant cause of morbidity and mortality in Sub-Saharan Africa and South Asia. While clinical antimalarials are efficacious when administered according to local guidelines, resistance to every class of antimalarials is a persistent problem. There is a constant need for new antimalarial therapeutics that complement parasite control strategies to combat malaria, especially in the tropics. In this work, nopol-based quinoline derivatives were investigated for their inhibitory activity against Plasmodium falciparum, one of the parasites that cause malaria. The nopyl-quinolin-8-yl amides (2–4) were moderately active against the asexual blood stage of chloroquine-sensitive strain Pf3D7 but inactive against chloroquine-resistant strains PfK1 and PfNF54. The nopyl-quinolin-4-yl amides and nopyl-quinolin-4-yl-acetates analogs were generally less active on all three strains. Interesting, the presence of a chloro substituent at C7 of the quinoline ring of amide 8 resulted in sub-micromolar EC(50) in the PfK1 strain. However, 8 was more than two orders of magnitude less active against Pf3D7 and PfNF54. Overall, the nopyl-quinolin-8-yl amides appear to share similar antimalarial profile (asexual blood-stage) with previously reported 8-aminoquinolines like primaquine. Future work will focus on investigating the moderately active and selective nopyl-quinolin-8-yl amides on the gametocyte or liver stages of Plasmodium falciparum and Plasmodium vivax.
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spelling pubmed-79176392021-03-02 Nopol-Based Quinoline Derivatives as Antiplasmodial Agents Nyamwihura, Rogers J. Zhang, Huaisheng Collins, Jasmine T. Crown, Olamide Ogungbe, Ifedayo Victor Molecules Article Malaria remains a significant cause of morbidity and mortality in Sub-Saharan Africa and South Asia. While clinical antimalarials are efficacious when administered according to local guidelines, resistance to every class of antimalarials is a persistent problem. There is a constant need for new antimalarial therapeutics that complement parasite control strategies to combat malaria, especially in the tropics. In this work, nopol-based quinoline derivatives were investigated for their inhibitory activity against Plasmodium falciparum, one of the parasites that cause malaria. The nopyl-quinolin-8-yl amides (2–4) were moderately active against the asexual blood stage of chloroquine-sensitive strain Pf3D7 but inactive against chloroquine-resistant strains PfK1 and PfNF54. The nopyl-quinolin-4-yl amides and nopyl-quinolin-4-yl-acetates analogs were generally less active on all three strains. Interesting, the presence of a chloro substituent at C7 of the quinoline ring of amide 8 resulted in sub-micromolar EC(50) in the PfK1 strain. However, 8 was more than two orders of magnitude less active against Pf3D7 and PfNF54. Overall, the nopyl-quinolin-8-yl amides appear to share similar antimalarial profile (asexual blood-stage) with previously reported 8-aminoquinolines like primaquine. Future work will focus on investigating the moderately active and selective nopyl-quinolin-8-yl amides on the gametocyte or liver stages of Plasmodium falciparum and Plasmodium vivax. MDPI 2021-02-14 /pmc/articles/PMC7917639/ /pubmed/33673007 http://dx.doi.org/10.3390/molecules26041008 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 Article
Nyamwihura, Rogers J.
Zhang, Huaisheng
Collins, Jasmine T.
Crown, Olamide
Ogungbe, Ifedayo Victor
Nopol-Based Quinoline Derivatives as Antiplasmodial Agents
title Nopol-Based Quinoline Derivatives as Antiplasmodial Agents
title_full Nopol-Based Quinoline Derivatives as Antiplasmodial Agents
title_fullStr Nopol-Based Quinoline Derivatives as Antiplasmodial Agents
title_full_unstemmed Nopol-Based Quinoline Derivatives as Antiplasmodial Agents
title_short Nopol-Based Quinoline Derivatives as Antiplasmodial Agents
title_sort nopol-based quinoline derivatives as antiplasmodial agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917639/
https://www.ncbi.nlm.nih.gov/pubmed/33673007
http://dx.doi.org/10.3390/molecules26041008
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