Aminopropyl-Linked Quinoline-Triazole Hybrids with Enhanced Antiplasmodial Activity Targeting β-Hematin Formation

Abstract

Resistance of Plasmodium falciparum to current antimalarials necessitates new therapies. This preliminary study presents the design, synthesis, and characterization of novel 7-chloroquinoline-1,2,3-triazole hybrids incorporating aminopropyl linkers. Several compounds show submicromolar in vitro activity against both chloroquine-sensitive and -resistant strains. β-Hematin inhibition assays revealed strong activity, especially for a cationic iridium(III) complex (7), despite its limited cellular efficacy. The presence of an aminoalkyl linker, secondary amines, and metal coordination were found to be critical to enhanced antiplasmodial activity, supporting further development of these hybrids as promising antimalarial agents.