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

Molecules

Catherine Hemmert¹  Heinz Gornitzka¹  Álvaro Fernández Álvarez¹  Manel Ouji¹  Jean-Michel Augereau¹  Françoise Benoit-Vical¹  Guillaume Barnouin¹ 

[1] CNRS, Laboratoire de Chimie de Coordination (LCC), Université de Toulouse, UPS, INPT, 205 route de Narbonne, BP 44099, F-31077 Toulouse CEDEX 4, France;

关键词: malaria;    Plasmodium falciparum;    gold;    NHC-ligands;    hybrid molecules;    drug resistance;   

DOI  :  10.3390/molecules25122817

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown