title: Molecular modeling and UV-vis spectroscopic studies on the mechanism of action of reversed chloroquine (RCQ).
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.
authors.affiliation: Programa de Pós-graduação em Fármaco e Medicamentos, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Av Prof Lineu Prestes, 580 Bl. 13 sup, 05508-000 São Paulo, Brazil. vaotelo@yahoo.com.br
authors.forename: Vanessa A
authors.initials: VA
authors.lastname: Otelo
authors.forename: Antonio C
authors.initials: AC
authors.lastname: Sant'Ana
authors.forename: Dalva L A
authors.initials: DL
authors.lastname: de Faria
authors.forename: Carla M S
authors.initials: CM
authors.lastname: Menezes
mesh_terms: D000634:Aminoquinolines / Q000737:chemistry*; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002738:Chloroquine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D003984:Dibenzazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006427:Hemin / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007099:Imipramine / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D010963:Plasmodium falciparum / Q000187:drug effects; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000634:Aminoquinolines; D000962:Antimalarials; D003984:Dibenzazepines; D006427:Hemin; D002738:Chloroquine; C001920:4-aminoquinoline; D007099:Imipramine