Hitting drug-resistant malaria infection with triazole-linked flavonoid-chloroquine hybrid compounds.

: Malaria represents the major parasitic disease in tropical regions, and the development of new potent drugs is of pivotal importance. In this study, a series of hybrid molecules were designed by linking the 7-chloroquinoline core of chloroquine to different fluorinated flavonoid-related scaffolds. : Compounds were prepared by exploiting the click chemistry approach, allowing the introduction of a 1,2,3-triazole, a privileged structural motif in antiparasitic dug discovery. Compounds and were the most interesting and were endowed with the highest activity, mainly against a resistant strain. They also inhibited hemozoin formation, and was more effective than chloroquine against stage V gametocytes. The homoisoflavone core is a new, promising antimalarial scaffold that deserves further investigation.