芳香二脒对婴儿利什曼原虫前鞭毛体中腐胺摄取的抑制作用。

Putrescine uptake inhibition by aromatic diamidines in Leishmania infantum promastigotes.

作者信息

Reguera R, Balaña Fouce R, Cubria J C, Alvarez Bujidos M L, Ordoñez D

机构信息

Dpto Fisiología, Farmacología y Toxicología, Ftad de Veterinaria, Universidad de León, Spain.

出版信息

Biochem Pharmacol. 1994 May 18;47(10):1859-66. doi: 10.1016/0006-2952(94)90316-6.

DOI:10.1016/0006-2952(94)90316-6

PMID:8204103

Abstract

The effect of a series of aromatic diamidines has been tested on Leishmania infantum promastigotes in both culture growth and putrescine uptake. The EC50 values calculated by means of dose-response curves were 45, 80, 165, 259 and 600 microM for 4', 6-diamidino-2-phenylindole (DAPI), dibromo propamidine, pentamidine 2-hydroxy stilbamidine and stilbamidine, respectively, although no inhibitory effects on cell growth were found at 1 mM propamidine, phenamidine and amicarbalide. When these compounds were kinetically analysed for putrescine uptake using Lineweaver-Burk plots, the Ki values reached were: DAPI, 15 microM; pentamidine, 3 microM; dibromo propamidine, 7 microM; 2-hydroxy stilbamidine, 21 microM; stilbamidine, 20 microM; propamidine, 25 microM; and phenamidine, 95 microM. Amicarbalide, however, was not able to reduce putrescine uptake to a significant extent, even at the highest concentration studied of 1 mM.

摘要

已经在培养生长和腐胺摄取方面测试了一系列芳香二脒对婴儿利什曼原虫前鞭毛体的作用。通过剂量反应曲线计算得出的4′,6-二脒基-2-苯基吲哚（DAPI）、二溴丙脒、喷他脒、2-羟基司替巴脒和司替巴脒的EC50值分别为45、80、165、259和600微摩尔，不过在1毫摩尔丙脒、苯脒和双脒苯脲时未发现对细胞生长有抑制作用。当使用Lineweaver-Burk图对这些化合物摄取腐胺进行动力学分析时，得到的Ki值为：DAPI，15微摩尔；喷他脒，3微摩尔；二溴丙脒，7微摩尔；2-羟基司替巴脒，21微摩尔；司替巴脒，20微摩尔；丙脒，25微摩尔；苯脒，95微摩尔。然而，即使在研究的最高浓度1毫摩尔时，双脒苯脲也不能显著降低腐胺摄取。