Hybrid Gold(I) NHC-Artemether Complexes to Target Falciparum Malaria Parasites.

Autor: Ouji M; CNRS, Laboratoire de Chimie de Coordination (LCC), Université de Toulouse, UPS, INPT, 205 route de Narbonne, BP 44099, F-31077 Toulouse CEDEX 4, France.; Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, 31077 Toulouse, France., Barnoin G; CNRS, Laboratoire de Chimie de Coordination (LCC), Université de Toulouse, UPS, INPT, 205 route de Narbonne, BP 44099, F-31077 Toulouse CEDEX 4, France., Fernández Álvarez Á; CNRS, Laboratoire de Chimie de Coordination (LCC), Université de Toulouse, UPS, INPT, 205 route de Narbonne, BP 44099, F-31077 Toulouse CEDEX 4, France., Augereau JM; CNRS, Laboratoire de Chimie de Coordination (LCC), Université de Toulouse, UPS, INPT, 205 route de Narbonne, BP 44099, F-31077 Toulouse CEDEX 4, France.; Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, 31077 Toulouse, France., Hemmert C; CNRS, Laboratoire de Chimie de Coordination (LCC), Université de Toulouse, UPS, INPT, 205 route de Narbonne, BP 44099, F-31077 Toulouse CEDEX 4, France., Benoit-Vical F; CNRS, Laboratoire de Chimie de Coordination (LCC), Université de Toulouse, UPS, INPT, 205 route de Narbonne, BP 44099, F-31077 Toulouse CEDEX 4, France.; Institut de Pharmacologie et de Biologie Structurale, IPBS, Université de Toulouse, CNRS, UPS, 31077 Toulouse, France.; INSERM, Institut National de la Santé et de la Recherche Médicale, 31024 Toulouse, France., Gornitzka H; CNRS, Laboratoire de Chimie de Coordination (LCC), Université de Toulouse, UPS, INPT, 205 route de Narbonne, BP 44099, F-31077 Toulouse CEDEX 4, France.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2020 Jun 18; Vol. 25 (12). Date of Electronic Publication: 2020 Jun 18.
DOI: 10.3390/molecules25122817
Abstrakt: The emergence of Plasmodium falciparum parasites, responsible for malaria disease, resistant to antiplasmodial drugs including the artemisinins, represents a major threat to public health. Therefore, the development of new antimalarial drugs or combinations is urgently required. In this context, several hybrid molecules combining a dihydroartemisinin derivative and gold(I) N-heterocyclic carbene (NHC) complexes have been synthesized based on the different modes of action of the two compounds. The antiplasmodial activity of these molecules was assessed in vitro as well as their cytotoxicity against mammalian cells. All the hybrid molecules tested showed efficacy against P. falciparum , in a nanomolar range for the most active, associated with a low cytotoxicity. However, cross-resistance between artemisinin and these hybrid molecules was evidenced. These results underline a fear about the risk of cross-resistance between artemisinins and new antimalarial drugs based on an endoperoxide part. This study thus raises concerns about the use of such molecules in future therapeutic malaria policies.
Databáze: MEDLINE
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