Antimalarial activity of isoquine against Kenyan Plasmodium falciparum clinical isolates and association with polymorphisms in pfcrt and pfmdr1 genes

The use of amodiaquine in prophylaxis is associated with serious toxicity, resulting from its metabolic conversion into a reactive quinone-imine metabolite by the hepatic cytochrome P450. To circumvent this toxicity, several amodiaquine analogues that lack the potential to form a quinone-imine derivative, while retaining antimalarial activity, have been designed. Isoquine is one of these promising molecules that has already reached Phase I clinical trials in humans.