Haematin (haem) polymerization and its inhibition by quinoline antimalarials.
Haematin (ferriprotoporphyrin IX) is released from haemoglobin during its degradation in the malarial parasites' food vacuole and is detoxified by its polymerization into a form of beta-haematin called haemozoin, or malarial pigment. This process is protein independent in vitro. Quinoline antimalarial blood schizonticides accumulate in the food vacuole and may inhibit haematin polymerization by binding to haematin and preventing its incorporation into the growing haemozoin chain. Drug resistance to quinolines is thought to be due to reduced accumulation of the drug in the food vacuole. As some quinolines overcome this resistance, quinolines, as a class, remain a potential source of future antimalarial drugs.
Ridley
R G
RG
Pharmaceuticals Division (PRPI), F. Hoffmann-La Roche, Basel, Switzerland. robert_g.ridley@roche.com
Dorn
A
A
Vippagunta
S R
SR
Vennerstrom
J L
JL
D000818:Animals; D000962:Antimalarials / Q000378:metabolism / Q000494:pharmacology*; D006420:Hemeproteins; D006427:Hemin / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D010860:Pigments, Biological / Q000378:metabolism; D010961:Plasmodium / Q000187:drug effects; D011108:Polymers; D011804:Quinolines / Q000378:metabolism / Q000494:pharmacology*; D014617:Vacuoles / Q000378:metabolism
D000962:Antimalarials; D006420:Hemeproteins; D010860:Pigments, Biological; D011108:Polymers; D011804:Quinolines; C020753:hemozoin; D006427:Hemin