Quinoline anti-malarial drugs inhibit spontaneous formation of beta-haematin (malaria pigment).
Polymerisation of haematin to beta-haematin (haemozoin or malaria pigment) in acidic acetate solutions was studied using infrared spectroscopy. The reaction was found to occur spontaneously between 6 and 65 degrees C, in 0.1-4.5 M acetate and pH 4.2-5.0. The anti-malarial drugs quinine, chloroquine and amodiaquin were found to block spontaneous beta-haematin formation, while the anti-malarially inactive 9-epiquinine and 8-hydroxyquinoline had no effect on the reaction, as did primaquine, a drug which is active only against exo-erythrocytic stages of infection. It is argued that the intra-erythrocytically active anti-malarial agents act by binding to haematin, blocking beta-haematin formation and leaving toxic haematin in the parasite food vacuoles.
Egan
T J
TJ
Department of Chemical Pathology, Red Cross War Memorial Children's Hospital, Rondebosch, South Africa.
Ross
D C
DC
Adams
P A
PA
D000962:Antimalarials / Q000494:pharmacology*; D006420:Hemeproteins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D010860:Pigments, Biological / Q000378:metabolism*; D011108:Polymers; D012995:Solubility; D013696:Temperature
D000962:Antimalarials; D006420:Hemeproteins; D010860:Pigments, Biological; D011108:Polymers; C020753:hemozoin