Molecular modeling and UV-vis spectroscopic studies on the mechanism of action of reversed chloroquine (RCQ).

Bioorg Med Chem Lett

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.

Published: January 2011

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.

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http://dx.doi.org/10.1016/j.bmcl.2010.11.019DOI Listing

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