Mercaptopyridine-N-oxide, an NADH-fumarate reductase inhibitor, blocks Trypanosoma cruzi growth in culture and in infected myoblasts.
Mercaptopyridine-N-oxide, an NADH-fumarate reductase inhibitor, blocks Trypanosoma cruzi growth in culture and in infected myoblasts.
复制标题
巯基吡啶-N-氧化物是一种 NADH-富马酸还原酶抑制剂，可阻断培养物和感染的成肌细胞中克氏锥虫的生长。
DOI：
10.1111/j.1574-6968.1999.tb13623.x
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发表时间：
1999
影响因子：
2.1
通讯作者：
Docampo,R
中科院分区：
文献类型：
--
作者：
Turrens,JF;Newton,CL;Zhong,L;Hernandez,FR;Whitfield,J;Docampo,R
在哺乳动物细胞中没有发现NADH-延胡索酸还原酶，但它存在于几种寄生原生动物中，包括引起恰加斯病的寄生虫克氏锥虫（Trypanosoma cruzi）。本研究表明，药物2-巯基吡啶-N-氧化物（MPNO）抑制从T. cruzi（ID 50 = 35 µ M）。当加入完整细胞中时，MPNO抑制T.培养物中的cruziepimastigotes（ID 50 = 0.08 μ M）以及哺乳动物成肌细胞拜特的感染。cruzitripomastigotes（ID 50 = 20 µ M）。在2.4 μ M的浓度下，MPNO还抑制培养的哺乳动物成肌细胞中无鞭毛体（细胞内分裂形式）的生长。在培养基中补充5 mM琥珀酸（富马酸还原酶的产物）可以部分防止MPNO对上鞭毛体生长的抑制。此外，MPNO抑制琥珀酸的积累，在培养的epimastigotes，通过高效液相色谱法测定。虽然MPNO可能有其他细胞内的目标，除了延胡索酸还原酶，这些结果支持的假设，抑制延胡索酸还原酶的化合物可能是潜在的化疗药物对恰加斯病。
The enzyme NADH-fumarate reductase is not found in mammalian cells but it is present in several parasitic protozoa includingTrypanosoma cruzi, the parasite that causes Chagas' disease. This study shows that the drug 2-mercaptopyridine-N-oxide (MPNO) inhibits NADH-fumarate reductase purified fromT. cruzi(ID50=35 µM). When added to intact cells, MPNO inhibited the growth ofT. cruziepimastigotes in culture (ID50=0.08 µM) as well as the infection of mammalian myoblasts byT. cruzitrypomastigotes (ID50=20 µM). At a concentration of 2.4 µM, MPNO also inhibited the growth of amastigotes (intracellular dividing forms) in cultured mammalian myoblasts. Supplementation of culture media with 5 mM succinate, the product of fumarate reductase, partially protected against the inhibition of the growth of epimastigotes by MPNO. Moreover, MPNO inhibited the accumulation of succinate in cultures of epimastigotes, as measured by high performance liquid chromatography. Although MPNO may have other intracellular targets in addition to fumarate reductase, these results support the hypothesis that compounds which inhibit the enzyme fumarate reductase may be potential chemotherapeutic agents against ChagasȲ disease.