别嘌呤醇核糖核苷及相关化合物别嘌呤醇、硫嘌呤醇、硫嘌呤醇核糖核苷、以及间型霉素B、杀稻瘟菌素和勒皮定WR6026的抗利什曼原虫作用。

Anti-leishmanial effect of allopurinol ribonucleoside and the related compounds, allopurinol, thiopurinol, thiopurinol ribonucleoside, and of formycin B, sinefungin and the lepidine WR6026.

作者信息

Neal R A, Croft S L, Nelson D J

出版信息

Trans R Soc Trop Med Hyg. 1985;79(1):122-8. doi: 10.1016/0035-9203(85)90255-x.

Abstract

Allopurinol and allopurinol ribonucleoside tested in vitro and in vivo for activity against Leishmania donovani. Activity in vitro was low against the amastigote form of this parasite with ED50 values of the order of 54 and 96 microM and 86 and 213 microM respectively for the two compounds. In vivo inhibition of up to 47% was achieved with allopurinol ribonucleoside given in the drinking water. However, low blood levels were found in the mouse relative to those in man. Low in vivo activity was also seen with allopurinol ribonucleoside against L. major and other species of Leishmania causing cutaneous lesions. The metabolism of allopurinol ribonucleoside in aldehyde oxidase deficient mice (inbred strains DBA/1, DBA/2) resembled that of man, but the antileishmanial activity remained low. Other compounds, formycin B, sinefungin and the lepidine WR6026 were highly active against mice infected with L. donovani or L. major.

摘要

对别嘌呤醇和别嘌呤醇核糖核苷进行了体外和体内抗杜氏利什曼原虫活性测试。两种化合物对该寄生虫无鞭毛体形式的体外活性较低，ED50值分别约为54和96微摩尔以及86和213微摩尔。饮用含别嘌呤醇核糖核苷的水可在体内实现高达47%的抑制率。然而，相对于人类，在小鼠体内发现其血药浓度较低。别嘌呤醇核糖核苷对硕大利什曼原虫和其他引起皮肤病变的利什曼原虫物种的体内活性也较低。在醛氧化酶缺陷小鼠（近交系DBA/1、DBA/2）中，别嘌呤醇核糖核苷的代谢与人相似，但其抗利什曼原虫活性仍然较低。其他化合物，如间型霉素B、西奈芬净和勒皮定WR6026对感染杜氏利什曼原虫或硕大利什曼原虫的小鼠具有高度活性。