Synergistic interaction of a chloroquine metabolite with chloroquine against drug-resistant malaria parasites

Abstract

We have previously shown that structural modification of chlorpromazine to introduce a basic side chain converts this chloroquine (CQ) resistance- reversing agent into a compound that has activity against Plasmodium falciparum in vitro [Biochem. Pharmacol. 63 (2002) 833]. In an effort to further dissect the structural features that determine quinoline antimalarial activity and drug resistance-reversing activity, we have studied a series of aminoquinolines that are structurally related to CQ. We have analysed their haematin-binding activities, their antimalarial activities and their abilities to synergise the effect of CQ against drug-resistant P. falciparum. We found that a number of the ami..