The role of haem in the activity of chloroquine and related antimalarial drugs

Advances made over the last decade indicate that the mechanism of action of important antimalarial agents, such as chloroquine, involves formation of pi-pi complexes between drugs and ferriprotoporphyrin IX. This process is b elieved to block the detoxification of host haemoglobin-derived haem in the food vacuole of the parasite. Detoxification of haem occurs via conversion to a coordination polymer involving the formation of an Fe(III)-carboxylat e bond between the propionate group of one ferriprotoporphyrin IX molecule and the Fe(III) centre of the next. This compound is known as malaria pigme nt or haemozoin in vivo, but can also be prepared synthetically, in which c ase it is referred to as beta-haematin. Literature relating to the structur e and mechanism of formation of haemozoin/beta-haematin, the mechanism of a ction of the drugs and thermodynamics and structures of ferriprotoporphyrin M-drug complexes is reviewed. (C) 1999 Elsevier Science S.A. All rights re served.