Riscoe M K, Ferro A J, Fitchen J H
Medical Research Service, Portland Veterans Administration Medical Center, Oregon 97207.
Antimicrob Agents Chemother. 1988 Dec;32(12):1904-6. doi: 10.1128/AAC.32.12.1904.
Since drug resistance and toxicity limit the use of available antiprotozoal agents, it is important that new drugs be developed as soon as possible. In this study, the method by which several protozoa degrade 5'-methylthioadenosine (MTA) was shown to differ from MTA catabolism in human cells. To exploit this metabolic difference, two analogs of methylthioribose (MTR), an MTA catabolite, were synthesized and found to be cytocidal to Plasmodium falciparum, Giardia lamblia, and Ochromonas malhamensis in vitro. In contrast, these analogs had no effect on cultured mammalian cells. Analogs of MTR represent a potential new class of antiprotozoal drugs.
由于耐药性和毒性限制了现有抗寄生虫药物的使用，尽快开发新药很重要。在本研究中，几种原生动物降解5'-甲硫基腺苷（MTA）的方法被证明与人类细胞中的MTA分解代谢不同。为了利用这种代谢差异，合成了MTA分解代谢产物甲硫基核糖（MTR）的两种类似物，发现它们在体外对恶性疟原虫、蓝氏贾第鞭毛虫和马尔姆赭滴虫具有细胞毒性。相比之下，这些类似物对培养的哺乳动物细胞没有影响。MTR类似物代表了一类潜在的新型抗寄生虫药物。
