Building on Surface-Active Ionic Liquids for the Rescuing of the Antimalarial Drug Chloroquine
Ana Teresa Silva, Lis Lobo, Isabel S. Oliveira, Joana Gomes, Cátia Teixeira, Fátima Nogueira, Eduardo F. Marques, Ricardo Ferraz, Paula Gomes
Abstract
Ionic liquids derived from classical antimalarials are emerging as a new approach towards the cost-effective rescuing of those drugs. Herein, we disclose novel surface-active ionic liquids derived from chloroquine and natural fatty acids whose antimalarial activity in vitro was found to be superior to that of the parent drug. The most potent ionic liquid was the laurate salt of chloroquine, which presented IC50 values of 4 and 110 nM against a chloroquine-sensitive and a chloroquine-resistant strain of Plasmodium falciparum, respectively, corresponding to an 11- and 6-fold increase in potency as compared to the reference chloroquine bisphosphate salt against the same strains. This unprecedented report opens new perspectives in both the fields of malaria chemotherapy and of surface-active ionic liquids derived from active pharmaceutical ingredients.