Antiplasmodial, β-haematin inhibition, antitrypanosomal and cytotoxic activity in vitro of novel 4-aminoquinoline 2-imidazolines

Abstract

A novel series of 4-aminoquinoline-containing 2-imidazolines were synthesized via a one-pot 3-component condensation reaction of amine, aldehyde and isocyanoacetate. The products were obtained in high yield as well as purity and were evaluated directly against two strains of Plasmodium falciparum and Trypanosoma brucei. Compound 21 was the most active across all parasites with ED₅₀ = 3.3 nM against a chloroquine (CQ)-sensitive 3D7 strain, ED₅₀ = 33 nM against a CQ-resistant K1 strain and ED₅₀ = 70 nM against T. brucei. Several compounds were able to inhibit formation of β-haematinin vitro, suggesting haemozoin formation in the malaria parasite as a possible target. On the other hand, evaluation against a human KB cell line revealed that the compounds were generally non-cytotoxic to the host cells.