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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:21

Article

Otelo, Vanessa A.¹  Sant'Ana, Antonio C.²  de Faria, Dalva L. A.²  Menezes, Carla M. S.¹ 

[1] Univ Sao Paulo, Fac Ciencias Farmaceut, Programa Posgrad Farmaco & Medicamentos, BR-05508000 Sao Paulo, Brazil

[2] Univ Sao Paulo, Inst Quim, Dept Quim Fundamental, BR-05508000 Sao Paulo, Brazil

关键词: Reversed chloroquine;    Chloroquine;    Heme;    Antimalarial;    Multiple ligand;   

DOI  :  10.1016/j.bmcl.2010.11.019

来源: Elsevier

【 摘 要 】

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. (C) 2010 Elsevier Ltd. All rights reserved.

【 授权许可】

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