Avila J L, Casanova M A
Antimicrob Agents Chemother. 1982 Sep;22(3):380-5. doi: 10.1128/AAC.22.3.380.
When assayed on promastigotes of 10 American Leishmania isolates (including Leishmania brasiliensis and mexicana species), 4-aminopyrazolopyrimidine (AAP) was severalfold more active than allopurinol as a leishmanistatic drug. There were some intraspecific and interspecific differences among the isolates in their susceptibility to the inhibitory effects of APP and allopurinol. APP-2'-deoxyriboside did not affect the 10 isolates tested. This was surprising, because allopurinol riboside has previously been shown to be more active than allopurinol. In all of the American Leishmania isolates tested, the metabolism of [14C]6-APP resulted in a high level of HPP-ribose-5'-P and lower levels of APP-ribose-5'-P, APP-ribose-5'-PP, and APP-ribose-5'-PPP. MP, LR, LBY, and JAP isolates strongly converted APP into APP derivatives, thus perhaps explaining their greater susceptibility to the inhibitory effects of APP. With the 10 American Leishmania isolates tested, several purines reversed the inhibitory effects of allopurinol, but only adenine countered the inhibitory effects of APP. This suggests biochemical differences in the mechanisms of action of allopurinol and APP. Finally, and contrary to previous claims, the reversal by purines of the allopurinol-induced growth inhibition was not a Leishmania species-specific effect.
在对10株美洲利什曼原虫分离株（包括巴西利什曼原虫和墨西哥利什曼原虫）的前鞭毛体进行检测时，4-氨基吡唑并嘧啶（AAP）作为一种抗利什曼原虫药物，其活性比别嘌呤醇高几倍。这些分离株在对AAP和别嘌呤醇抑制作用的敏感性方面存在种内和种间差异。AAP-2'-脱氧核糖苷对所检测的10株分离株没有影响。这很令人惊讶，因为之前已证明别嘌呤醇核糖苷比别嘌呤醇更具活性。在所有检测的美洲利什曼原虫分离株中，[14C]6-AAP的代谢产生了高水平的HPP-核糖-5'-P以及较低水平的AAP-核糖-5'-P、AAP-核糖-5'-PP和AAP-核糖-5'-PPP。MP、LR、LBY和JAP分离株能强烈地将AAP转化为AAP衍生物，这或许可以解释它们对AAP抑制作用更敏感的原因。在所检测的10株美洲利什曼原虫分离株中，几种嘌呤可逆转别嘌呤醇的抑制作用，但只有腺嘌呤能对抗AAP的抑制作用。这表明别嘌呤醇和AAP的作用机制存在生化差异。最后，与之前的说法相反，嘌呤对别嘌呤醇诱导的生长抑制的逆转并非利什曼原虫物种特异性效应。
