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

Author: Egan T.J.

Source: Mini Reviews in Medicinal Chemistry, Volume 1, Number 1, May 2001 , pp. 113-123(11)

Publisher: Bentham Science Publishers

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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