Quinoline anti‐malarial drugs inhibit spontaneous formation of β‐haematin (malaria pigment)

Polymerisation of haematin to β‐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°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 β‐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 β‐haematin formation and leaving toxic haematin in the parasite food vacuoles.