Girault S, Grellier P, Berecibar A, Maes L, Mouray E, Lemière P, Debreu M A, Davioud-Charvet E, Sergheraert C
UMR 8525 CNRS, Université de Lille II, Institut de Biologie et Institut Pasteur de Lille, 1 rue du Professeur Calmette, BP 447, 59021 Lille, France.
J Med Chem. 2000 Jul 13;43(14):2646-54. doi: 10.1021/jm990946n.
Forty bis(9-amino-6-chloro-2-methoxyacridines), in which acridine moieties are joined by alkanediamines, polyamines, or polyamines substituted by a side chain, were synthesized and tested for their in vitro activity upon the erythrocytic stage of Plasmodium falciparum, trypomastigote stage of Trypanosoma brucei, and amastigote stage of Trypanosoma cruzi and Leishmania infantum as well as for their cytotoxic effects upon MRC-5 cells. Results clearly showed the importance of the nature of the linker and of its side chain for antiparasitic activity, cytotoxicity, and cellular localization. Among several compounds devoid of cytotoxic effects at 25 microM upon MRC-5 cells, one displayed IC(50) values ranging from 8 to 18 nM against different P. falciparum strains while three others totally inhibited T. brucei at 1.56 microM.
合成了40种双（9-氨基-6-氯-2-甲氧基吖啶），其中吖啶部分通过链烷二胺、多胺或被侧链取代的多胺连接，并测试了它们对恶性疟原虫红细胞期、布氏锥虫锥鞭毛体期、克氏锥虫和婴儿利什曼原虫无鞭毛体期的体外活性，以及它们对MRC-5细胞的细胞毒性作用。结果清楚地表明，连接体的性质及其侧链对于抗寄生虫活性、细胞毒性和细胞定位至关重要。在对MRC-5细胞在25μM时无细胞毒性作用的几种化合物中，一种对不同恶性疟原虫菌株的IC50值在8至18 nM之间，而另外三种在1.56μM时完全抑制布氏锥虫。
