Berens R L, Marr J J, Looker D L, Nelson D J, LaFon S W
J Infect Dis. 1984 Oct;150(4):602-8. doi: 10.1093/infdis/150.4.602.
Strains of Trypanosoma cruzi differ in their susceptibilities to and metabolism of pyrazolopyrimidines. Allopurinol riboside can control but not eliminate infections with a sensitive strain in both tissue culture and mice. Formycin B, which proved to be greater than 10-fold more effective on a weight basis, showed a similar strain specificity but could eliminate an infection with a sensitive strain from tissue culture. However, this drug, unlike allopurinol riboside, was converted to toxic analogues of adenosine mono-, di-, and triphosphate by uninfected tissue culture cells. Thiopurinol and its riboside were effective against all strains unless culture was performed in purine-defined medium. Thus formycin B and allopurinol riboside appear to be good models for the design of antitrypanosomal agents. Suitable modification of the molecule may provide an effective chemotherapeutic agent.
克氏锥虫的不同菌株对吡唑并嘧啶的敏感性和代谢情况有所不同。别嘌呤醇核糖苷在组织培养和小鼠实验中都能控制但无法消除敏感菌株的感染。以重量计，证明效力比别嘌呤醇核糖苷大10倍以上的间型霉素B表现出类似的菌株特异性，但能从组织培养中消除敏感菌株的感染。然而，与别嘌呤醇核糖苷不同，这种药物会被未感染的组织培养细胞转化为一磷酸、二磷酸和三磷酸腺苷的毒性类似物。硫代嘌呤醇及其核糖苷对所有菌株都有效，除非在嘌呤限定培养基中进行培养。因此，间型霉素B和别嘌呤醇核糖苷似乎是设计抗锥虫药物的良好模型。对该分子进行适当修饰可能会提供一种有效的化疗药物。
