Synthesis and Antimalarial Activities of New Hybrid Atokel Molecules
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
Affiliations
Youzhi Li
Guangdong University of Technology School of Chemical Engineering and Light Industry no. 100 Waihuan Xi road Education Mega Center Guangzhou 510006 P. R. China
Anthony Loureiro
Laboratoire de Chimie de Coordination du CNRS LCC–CNRS Université de Toulouse Université Paul Sabatier 205 route de Narbonne, BP 44099 31077 Toulouse cedex 4 France
Dr. Michel Nguyen
Laboratoire de Chimie de Coordination du CNRS LCC–CNRS Université de Toulouse Université Paul Sabatier 205 route de Narbonne, BP 44099 31077 Toulouse cedex 4 France
Marion Laurent
Laboratoire de Chimie de Coordination du CNRS LCC–CNRS Université de Toulouse Université Paul Sabatier 205 route de Narbonne, BP 44099 31077 Toulouse cedex 4 France
Dr. Christian Bijani
Laboratoire de Chimie de Coordination du CNRS LCC–CNRS Université de Toulouse Université Paul Sabatier 205 route de Narbonne, BP 44099 31077 Toulouse cedex 4 France
Dr. Françoise Benoit‐Vical
Laboratoire de Chimie de Coordination du CNRS LCC–CNRS Université de Toulouse Université Paul Sabatier 205 route de Narbonne, BP 44099 31077 Toulouse cedex 4 France
Dr. Anne Robert
Laboratoire de Chimie de Coordination du CNRS LCC–CNRS Université de Toulouse Université Paul Sabatier 205 route de Narbonne, BP 44099 31077 Toulouse cedex 4 France
Prof. Dr. Yan Liu
Guangdong University of Technology School of Chemical Engineering and Light Industry no. 100 Waihuan Xi road Education Mega Center Guangzhou 510006 P. R. China
Prof. Dr. Bernard Meunier
Guangdong University of Technology School of Chemical Engineering and Light Industry no. 100 Waihuan Xi road Education Mega Center Guangzhou 510006 P. R. China
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.
