Synthesis and Antimalarial Activities of New Hybrid Atokel Molecules

Autor: Youzhi Li, Anthony Loureiro, Dr. Michel Nguyen, Marion Laurent, Dr. Christian Bijani, Dr. Françoise Benoit‐Vical, Dr. Anne Robert, Prof. Dr. Yan Liu, Prof. Dr. Bernard Meunier
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: ChemistryOpen, Vol 11, Iss 5, Pp n/a-n/a (2022)
Druh dokumentu: article
ISSN: 2191-1363
20220006
DOI: 10.1002/open.202200064
Popis: Abstract 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 (IC50=622 nm on an artemisinin‐resistant P. falciparum strain) and no cytotoxicity at 50 μm indicating a specific antiplasmodial mode of action.
Databáze: Directory of Open Access Journals
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