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Bioorg Med Chem Lett ; 21(1): 250-4, 2011 Jan 01.
Article in English | MEDLINE | ID: mdl-21095121

ABSTRACT

Reversed chloroquine (RCQ) is a multiple ligand compound active against chloroquine-sensitive and resistant falciparum malaria. It is composed by a 4-aminoquinoline moiety (like that present in chloroquine (CQ)) joined to imipramine (IMP), a modulating agent that also showed intrinsic antiplasmodial activity against Brazilian Plasmodium falciparum isolates resistant to CQ. Molecular modeling and ultraviolet-visible spectroscopy (UV-vis) studies strongly suggest that the interaction between RCQ and heme is predominant through the quinoline moiety in a mechanism of action similar to that observed for CQ.


Subject(s)
Aminoquinolines/chemistry , Antimalarials/chemistry , Chloroquine/analogs & derivatives , Chloroquine/chemistry , Dibenzazepines/chemistry , Molecular Dynamics Simulation , Antimalarials/chemical synthesis , Antimalarials/pharmacology , Chloroquine/chemical synthesis , Chloroquine/pharmacology , Dibenzazepines/chemical synthesis , Dibenzazepines/pharmacology , Hemin/chemistry , Hydrogen-Ion Concentration , Imipramine/chemistry , Plasmodium falciparum/drug effects , Spectrophotometry, Ultraviolet
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