Design, synthesis and anti-plasmodial evaluation in vitro of new 4-aminoquinoline isatin derivatives.

A new class of 4-aminoquinoline derivatives based on the natural product isatin scaffold were designed and synthesized for biological evaluation against three strains of the malaria parasite Plasmodium falciparum. These derivatives showed anti-plasmodial IC(50) values in the ranges of 1.3-0.

Application of multi-component reactions to antimalarial drug discovery. Part 1: Parallel synthesis and antiplasmodial activity of new 4-aminoquinoline Ugi adducts.

The synthesis of a new class of Ugi adducts incorporating the 4-aminoquinoline moiety is described. The novel compounds are active against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum with the best compound showing an IC(50) value of 73 nM against a resistant K1 strain.

Plasmodium falciparum cysteine protease falcipain-1 is not essential in erythrocytic stage malaria parasites.

Among potential new targets for antimalarial chemotherapy are Plasmodium falciparum cysteine proteases, known as falcipains. Falcipain-2 and falcipain-3 are food vacuole hemoglobinases that may have additional functions. The function of falcipain-1 remains uncertain.