分子模拟和紫外可见光谱研究逆转氯喹（RCQ）作用机制。

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

机构信息

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.

出版信息

Bioorg Med Chem Lett. 2011 Jan 1;21(1):250-4. doi: 10.1016/j.bmcl.2010.11.019. Epub 2010 Nov 5.

DOI:10.1016/j.bmcl.2010.11.019

PMID: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.

摘要

抗疟有效化合物 RCQ 是一种多配体化合物，对敏感和耐药恶性疟原虫均有活性。它由 4-氨基喹啉部分（与氯喹（CQ）相同）与丙咪嗪（IMP）组成，IMP 是一种调节剂，对巴西耐 CQ 的恶性疟原虫分离株也具有内在的抗疟原虫活性。分子建模和紫外可见光谱（UV-vis）研究强烈表明，RCQ 与血红素的相互作用主要通过喹啉部分，其作用机制与观察到的 CQ 相似。