阿莫地喹新类似物的合成及其抗疟活性

Synthesis and antimalarial activity of new analogues of amodiaquine.

作者信息

Delarue-Cochin Sandrine, Paunescu Emilia, Maes Louis, Mouray Elisabeth, Sergheraert Christian, Grellier Philippe, Melnyk Patricia

机构信息

UMR CNRS 8525, Université de Lille II, Institut Pasteur de Lille 1 rue du Professeur Calmette, B.P. 447, 59021 Lille cedex, France.

出版信息

Eur J Med Chem. 2008 Feb;43(2):252-60. doi: 10.1016/j.ejmech.2007.03.008. Epub 2007 Apr 3.

DOI:10.1016/j.ejmech.2007.03.008

PMID:17485145

Abstract

In order to determine the real significance of the 4'-phenolic group in the antimalarial activity and/or cytotoxicity of amodiaquine (AQ), analogues for which this functionality was shifted or modified were synthesized. Good in vitro antimalarial activity was obtained for compounds unable to form intramolecular hydrogen bond. Among the compounds synthesized, new amino derivative 5 displayed the greatest selectivity index towards the most CQ-resistant strain tested and was active in mice infected by Plasmodium berghei.

摘要

为了确定4'-酚羟基在阿莫地喹（AQ）抗疟活性和/或细胞毒性中的实际意义，合成了该官能团位置发生改变或经过修饰的类似物。对于无法形成分子内氢键的化合物，获得了良好的体外抗疟活性。在所合成的化合物中，新的氨基衍生物5对测试的最耐氯喹菌株表现出最大的选择性指数，并且对感染伯氏疟原虫的小鼠具有活性。