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Semi-Synthesis and Evaluation of Sargahydroquinoic Acid Derivatives as Potential Antimalarial Agents

Background: Malaria continues to present a major health problem, especially in developing countries. The development of new antimalarial drugs to counter drug resistance and ensure a steady supply of new treatment options is therefore an important area of research. Meroditerpenes have previously bee...

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Autores principales: Munedzimwe, Tatenda C., van Zyl, Robyn L., Heslop, Donovan C., Edkins, Adrienne L., Beukes, Denzil R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630221/
https://www.ncbi.nlm.nih.gov/pubmed/30939856
http://dx.doi.org/10.3390/medicines6020047
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author Munedzimwe, Tatenda C.
van Zyl, Robyn L.
Heslop, Donovan C.
Edkins, Adrienne L.
Beukes, Denzil R.
author_facet Munedzimwe, Tatenda C.
van Zyl, Robyn L.
Heslop, Donovan C.
Edkins, Adrienne L.
Beukes, Denzil R.
author_sort Munedzimwe, Tatenda C.
collection PubMed
description Background: Malaria continues to present a major health problem, especially in developing countries. The development of new antimalarial drugs to counter drug resistance and ensure a steady supply of new treatment options is therefore an important area of research. Meroditerpenes have previously been shown to exhibit antiplasmodial activity against a chloroquinone sensitive strain of Plasmodium falciparum (D10). In this study we explored the antiplasmodial activity of several semi-synthetic analogs of sargahydroquinoic acid. Methods: Sargahydroquinoic acid was isolated from the marine brown alga, Sargassum incisifolium and converted, semi-synthetically, to several analogs. The natural products, together with their synthetic derivatives were evaluated for their activity against the FCR-3 strain of Plasmodium falciparum as well as MDA-MB-231 breast cancer cells. Results: Sarganaphthoquinoic acid and sargaquinoic acid showed the most promising antiplasmodial activity and low cytotoxicity. Conclusions: Synthetic modification of the natural product, sargahydroquinoic acid, resulted in the discovery of a highly selective antiplasmodial compound, sarganaphthoquinoic acid.
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spelling pubmed-66302212019-08-19 Semi-Synthesis and Evaluation of Sargahydroquinoic Acid Derivatives as Potential Antimalarial Agents Munedzimwe, Tatenda C. van Zyl, Robyn L. Heslop, Donovan C. Edkins, Adrienne L. Beukes, Denzil R. Medicines (Basel) Article Background: Malaria continues to present a major health problem, especially in developing countries. The development of new antimalarial drugs to counter drug resistance and ensure a steady supply of new treatment options is therefore an important area of research. Meroditerpenes have previously been shown to exhibit antiplasmodial activity against a chloroquinone sensitive strain of Plasmodium falciparum (D10). In this study we explored the antiplasmodial activity of several semi-synthetic analogs of sargahydroquinoic acid. Methods: Sargahydroquinoic acid was isolated from the marine brown alga, Sargassum incisifolium and converted, semi-synthetically, to several analogs. The natural products, together with their synthetic derivatives were evaluated for their activity against the FCR-3 strain of Plasmodium falciparum as well as MDA-MB-231 breast cancer cells. Results: Sarganaphthoquinoic acid and sargaquinoic acid showed the most promising antiplasmodial activity and low cytotoxicity. Conclusions: Synthetic modification of the natural product, sargahydroquinoic acid, resulted in the discovery of a highly selective antiplasmodial compound, sarganaphthoquinoic acid. MDPI 2019-04-01 /pmc/articles/PMC6630221/ /pubmed/30939856 http://dx.doi.org/10.3390/medicines6020047 Text en © 2019 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
Munedzimwe, Tatenda C.
van Zyl, Robyn L.
Heslop, Donovan C.
Edkins, Adrienne L.
Beukes, Denzil R.
Semi-Synthesis and Evaluation of Sargahydroquinoic Acid Derivatives as Potential Antimalarial Agents
title Semi-Synthesis and Evaluation of Sargahydroquinoic Acid Derivatives as Potential Antimalarial Agents
title_full Semi-Synthesis and Evaluation of Sargahydroquinoic Acid Derivatives as Potential Antimalarial Agents
title_fullStr Semi-Synthesis and Evaluation of Sargahydroquinoic Acid Derivatives as Potential Antimalarial Agents
title_full_unstemmed Semi-Synthesis and Evaluation of Sargahydroquinoic Acid Derivatives as Potential Antimalarial Agents
title_short Semi-Synthesis and Evaluation of Sargahydroquinoic Acid Derivatives as Potential Antimalarial Agents
title_sort semi-synthesis and evaluation of sargahydroquinoic acid derivatives as potential antimalarial agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630221/
https://www.ncbi.nlm.nih.gov/pubmed/30939856
http://dx.doi.org/10.3390/medicines6020047
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