Amodiaquine accumulation in Plasmodium falciparum as a possible explanation for its superior antimalarial activity over chloroquine

摘要: Amodiaquine is a 4-aminoquinoline antimalarial whose structure similar to chloroquine. In contrast the wealth of information available about chloroquine accumulation and its relationship activity, little known uptake characteristics amodiaquine, drug that inherently more active against malaria parasites. this study we have investigated amodiaquine in Plasmodium falciparum vitro, order gain an insight into mechanisms responsible for superior activity over The driving force parasite 4-aminoquinolines proposed be transmembrane proton gradient maintained by vacuolar ATPase. present study, was greatly reduced, at steady state, absence glucose 0 degrees C indicating clear energy dependence uptake. shown 2- 3-fold greater than accumulation. This observation probably accounts amodiaquine's inherent but surprising given weaker base With mind evidence intraparasitic binding component 4-aminoquinolines. Differences affinity 'receptor' may partially explain vitro potency compared