Wang C C, Verham R, Cheng H W, Rice A, Wang A L
Biochem Pharmacol. 1984 Apr 15;33(8):1323-9. doi: 10.1016/0006-2952(84)90187-4.
Tritrichomonas foetus and Trichomonas vaginalis are both incapable of de novo purine nucleotide synthesis. Previous studies indicated that T. foetus relies mainly on the salvage of hypoxanthine and subsequent conversion of IMP to AMP and GMP, whereas T. vaginalis depends on direct conversions of exogenous adenosine to AMP and guanosine to GMP without much interconversion between the two nucleotides. These two different types of purine salvage suggest the possibility of differential sensitivities between the two species of trichomonad flagellates toward different purine antimetabolites. Mycophenolic acid, hadacidin, 8-azaguanine, and formycin B inhibited the growth of T. foetus but had no effect on T. vaginalis. Mycophenolic acid acted by blocking conversion of IMP to GMP, hadacidin inhibited conversion of IMP to AMP, and 8-azaguanine was incorporated into the T. foetus nucleotide pool, likely via hypoxanthine phosphoribosyl transferase. Formycin B was converted to 5'-monophosphate in T. foetus and inhibited the conversion of IMP to AMP. Its precise mechanism of action on T. foetus remains, however, to be elucidated. Alanosine, whose ribonucleotide derivative is a potent inhibitor of adenylosuccinate synthetase, had no effect on the growth or hypoxanthine incorporation in T. foetus, which may be due to the lack of conversion of alanosine to the ribonucleotide because of the absence of de novo purine nucleotide synthesis in parasites. Four adenosine analogs, adenine arabinoside, tubercidin, sangivamycin, and toyocamycin, were found inhibitory to the growth of T. vaginalis but showed little effect on T. foetus growth. Further investigations suggested that these four compounds acted on T. vaginalis by blocking incorporation of adenosine into the adenine nucleotide pool.
胎儿三毛滴虫和阴道毛滴虫都不能从头合成嘌呤核苷酸。先前的研究表明，胎儿三毛滴虫主要依赖次黄嘌呤的补救利用以及随后将肌苷酸（IMP）转化为腺苷酸（AMP）和鸟苷酸（GMP），而阴道毛滴虫则依赖于将外源性腺苷直接转化为AMP以及将鸟苷直接转化为GMP，两种核苷酸之间的相互转化很少。这两种不同类型的嘌呤补救利用表明，这两种毛滴虫对不同嘌呤抗代谢物的敏感性可能存在差异。霉酚酸、杀稻瘟菌素、8-氮鸟嘌呤和间型霉素B抑制了胎儿三毛滴虫的生长，但对阴道毛滴虫没有影响。霉酚酸通过阻断IMP向GMP的转化起作用，杀稻瘟菌素抑制IMP向AMP的转化，8-氮鸟嘌呤可能通过次黄嘌呤磷酸核糖转移酶掺入胎儿三毛滴虫的核苷酸池中。间型霉素B在胎儿三毛滴虫中转化为5'-单磷酸，并抑制IMP向AMP的转化。然而，其对胎儿三毛滴虫的确切作用机制仍有待阐明。丙氨酸，其核糖核苷酸衍生物是腺苷酸琥珀酸合成酶的有效抑制剂，对胎儿三毛滴虫的生长或次黄嘌呤掺入没有影响，这可能是由于寄生虫中缺乏从头嘌呤核苷酸合成，导致丙氨酸无法转化为核糖核苷酸。发现四种腺苷类似物，即阿糖腺苷、杀结核菌素、桑吉瓦霉素和丰加霉素，对阴道毛滴虫的生长有抑制作用，但对胎儿三毛滴虫的生长影响很小。进一步的研究表明，这四种化合物通过阻断腺苷掺入腺嘌呤核苷酸池来作用于阴道毛滴虫。
