Structure-function relationships in chloroquine and related 4-aminoquinoline antimalarials.
Recent publication have provided strong evidence that activity and cellular uptake of 4-aminoquinoline antimalarials depends on vacuolar haemoglobin degradation and that haematin is the drug target. Studies on haematin-quinoline interactions have provided insight into the structural requirements for these interactions and indications are that 4-aminoquinolines may act by inhibiting haemozoin formation. Structural requirements for this activity have also been reported recently and have led to construction of an empirical structure-function relationship for 4-aminoquinolines.
Egan
T J
TJ
Department of Chemistry, University of Cape Town, Private Bag Rondebosch 7701, South Africa. tegan@psipsy.uct.ac.za
D000634:Aminoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D002738:Chloroquine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D006454:Hemoglobins / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008288:Malaria / Q000145:classification / Q000188:drug therapy*; D008958:Models, Molecular; D008968:Molecular Conformation; D010961:Plasmodium / Q000187:drug effects; D013329:Structure-Activity Relationship
D000634:Aminoquinolines; D000962:Antimalarials; D006454:Hemoglobins; D002738:Chloroquine; C001920:4-aminoquinoline