Nakayama H, Desrivot J, Bories C, Franck X, Figadère B, Hocquemiller R, Fournet A, Loiseau P M
Department of Tropical Medicine, Casilla de Correo 2511, Instituto de Investigaciones en Ciencias de la Salud Asunción, Universidad Nacional de Asuncion, Asuncion, Paraguay.
Biomed Pharmacother. 2007 Feb-Apr;61(2-3):186-8. doi: 10.1016/j.biopha.2007.02.001. Epub 2007 Feb 26.
The in vitro activity of a new analogue of 2-alkenylquinoline (2-nitrilquinoline or NQ) against Leishmania donovani was compared to oral reference drug miltefosine (HePC). IC(50) of NQ was found at 38.6 microM against promastigotes and 2.4 microM against intramacrophage amastigotes. In vivo evaluation in the L. donovani Balb/c mice model indicated that oral treatments at 12.5 and 25 mg/kg for 10 consecutive days significantly reduced the parasite burden in the liver by 68.9 and 68.5%, respectively. This activity was similar to those of HePC at 7.5 mg/kg for 10 days which reduced the parasite burden in liver by 72.5%. The present study shows the positive contribution of a nitril substitute being added into the alkenyl chain branched at the 2-position of the quinoline ring to the antileishmanial activity. In addition, any apparent toxicological disorder was observed during the experiments.
将一种新型2-烯基喹啉类似物（2-腈基喹啉或NQ）对杜氏利什曼原虫的体外活性与口服参比药物米替福新（己基磷酸胆碱）进行了比较。发现NQ对前鞭毛体的半数抑制浓度（IC50）为38.6微摩尔，对巨噬细胞内无鞭毛体的IC50为2.4微摩尔。在杜氏利什曼原虫Balb/c小鼠模型中的体内评估表明，连续10天以12.5和25毫克/千克的剂量口服给药，可使肝脏中的寄生虫负荷分别显著降低68.9%和68.5%。该活性与连续10天以7.5毫克/千克的剂量给予米替福新的活性相似，后者可使肝脏中的寄生虫负荷降低72.5%。本研究表明，在喹啉环2位分支的烯基链中添加腈基取代基对抗利什曼活性有积极贡献。此外，在实验过程中未观察到任何明显的毒理学紊乱。
