Quinolines block every step of malaria heme crystal growth

Malaria is a lethal zoonotic disease that has impacted human survival and indeed, the history of human civilizations worldwide. The first effective treatment for malaria was reported in 1632 with the use of quinine extracts from the bark of the cinchona tree. Since that time, quinoline compounds have been used as both prophylactic and therapeutic drugs in every type of malarial treatment. Almost 400 y later, the molecular mechanism of quinoline action is brought into focus by Olafson et al. in their study of the step inhibition of heme crystal growth (1). To put the significance of their findings into perspective, identification of hemozoin was integral to the 1880 malaria diagnosis by Laveran (2). Sometimes referred to as malaria pigment, this crystalline heme is synthesized by parasites intracellularly and was identified as a recognizable black round body with thin filaments on the periphery from exflagellation of the gametocytes in unstained human erythrocytes (2). Ronald Ross also found malarial pigment outside the Anopheles stomach to implicate the mosquito as the vector (3). In 1911, Brown (4) stated that hematin was a component of hemozoin, distinct from melanin. He also postulated malaria pigment was an impure byproduct of hemoglobin degradation. For the next 80 y, malariologists neglected hemozoin study until Slater and Cerami proved that hemozoin was pure heme by elemental analysis (5) and, importantly, that quinolines inhibited hemozoin growth (6). Decades …