Quinoline antimalarials: Mechanisms of action and resistance

Abstract

The quinoline-containing antimalarial drugs, chloroquine, quinine and mefloquine, are a vital part of our chemotherapeutic armoury against malaria. These drugs are thought to act by interfering with the digestion of haemoglobin in the blood stages of the malaria life cycle. Chloroquine is a dibasic drug which diffuses down the pH gradient to accumulate about a 1000-fold in the acidic vacuole of the parasite. The high intravacuolar concentration of chloroquine is proposed to inhibit the polymerisation of haem. As a result, the haem which is released during haemoglobin breakdown builds up to poisonous levels, thereby killing the parasite with its own toxic waste. The more lipophilic quinolinem..