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Synthesis and Antimalarial Activities of New Hybrid Atokel Molecules
The currently spreading resistance of the malaria parasite Plasmodium falciparum to artemisinin‐based combination therapies makes an urgent need for new efficient drugs. Aiming to kill artemisinin‐resistant Plasmodium, a series of novel hybrid drugs named Atokels were synthesized and characterized....
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9092290/ https://www.ncbi.nlm.nih.gov/pubmed/35543215 http://dx.doi.org/10.1002/open.202200064 |
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author | Li, Youzhi Loureiro, Anthony Nguyen, Michel Laurent, Marion Bijani, Christian Benoit‐Vical, Françoise Robert, Anne Liu, Yan Meunier, Bernard |
author_facet | Li, Youzhi Loureiro, Anthony Nguyen, Michel Laurent, Marion Bijani, Christian Benoit‐Vical, Françoise Robert, Anne Liu, Yan Meunier, Bernard |
author_sort | Li, Youzhi |
collection | PubMed |
description | The currently spreading resistance of the malaria parasite Plasmodium falciparum to artemisinin‐based combination therapies makes an urgent need for new efficient drugs. Aiming to kill artemisinin‐resistant Plasmodium, a series of novel hybrid drugs named Atokels were synthesized and characterized. Atokels are based on an 8‐amino‐ or 8‐hydroxyquinoline entity covalently bound to a 1,4‐naphthoquinone through a polyamine linker. These drugs have been designed to target the parasite mitochondrion by their naphthoquinone moiety reminiscent of the antimalarial drug atovaquone, and to trigger a damaging oxidative stress due to their ability to chelate metal ions in order to generate redox active complexes in situ. The most effective Atokel drug shown a promising antimalarial activity (IC(50)=622 nm on an artemisinin‐resistant P. falciparum strain) and no cytotoxicity at 50 μm indicating a specific antiplasmodial mode of action. |
format | Online Article Text |
id | pubmed-9092290 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90922902022-05-18 Synthesis and Antimalarial Activities of New Hybrid Atokel Molecules Li, Youzhi Loureiro, Anthony Nguyen, Michel Laurent, Marion Bijani, Christian Benoit‐Vical, Françoise Robert, Anne Liu, Yan Meunier, Bernard ChemistryOpen Research Articles The currently spreading resistance of the malaria parasite Plasmodium falciparum to artemisinin‐based combination therapies makes an urgent need for new efficient drugs. Aiming to kill artemisinin‐resistant Plasmodium, a series of novel hybrid drugs named Atokels were synthesized and characterized. Atokels are based on an 8‐amino‐ or 8‐hydroxyquinoline entity covalently bound to a 1,4‐naphthoquinone through a polyamine linker. These drugs have been designed to target the parasite mitochondrion by their naphthoquinone moiety reminiscent of the antimalarial drug atovaquone, and to trigger a damaging oxidative stress due to their ability to chelate metal ions in order to generate redox active complexes in situ. The most effective Atokel drug shown a promising antimalarial activity (IC(50)=622 nm on an artemisinin‐resistant P. falciparum strain) and no cytotoxicity at 50 μm indicating a specific antiplasmodial mode of action. John Wiley and Sons Inc. 2022-05-11 /pmc/articles/PMC9092290/ /pubmed/35543215 http://dx.doi.org/10.1002/open.202200064 Text en © 2022 The Authors. Published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Li, Youzhi Loureiro, Anthony Nguyen, Michel Laurent, Marion Bijani, Christian Benoit‐Vical, Françoise Robert, Anne Liu, Yan Meunier, Bernard Synthesis and Antimalarial Activities of New Hybrid Atokel Molecules |
title | Synthesis and Antimalarial Activities of New Hybrid Atokel Molecules |
title_full | Synthesis and Antimalarial Activities of New Hybrid Atokel Molecules |
title_fullStr | Synthesis and Antimalarial Activities of New Hybrid Atokel Molecules |
title_full_unstemmed | Synthesis and Antimalarial Activities of New Hybrid Atokel Molecules |
title_short | Synthesis and Antimalarial Activities of New Hybrid Atokel Molecules |
title_sort | synthesis and antimalarial activities of new hybrid atokel molecules |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9092290/ https://www.ncbi.nlm.nih.gov/pubmed/35543215 http://dx.doi.org/10.1002/open.202200064 |
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