Structure-Function Relationships in Chloroquine and Related 4-Aminoquinoline Antimalarials

Timothy   J.   Egan

doi:10.2174/1389557013407188

Abstract

Recent publications 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.

Keywords: Aminoquinoline Antimalarials, haematin quinoline interactions, plasmepsins, oxidative assault, parasitised red cells, haemoglobin degradation, DMSO complexes, coplanar interaction, amodiaquine analogue tebuquine, haem-polymerase, vacuolar pH