Buchholz Kathrin, Comini Marcelo A, Wissenbach Dirk, Schirmer R Heiner, Krauth-Siegel R Luise, Gromer Stephan
Biochemie-Zentrum der Universität Heidelberg, INF 504, D-69120 Heidelberg, Germany.
Mol Biochem Parasitol. 2008 Jul;160(1):65-9. doi: 10.1016/j.molbiopara.2008.03.006. Epub 2008 Mar 21.
Methylene blue (MB) is known to have trypanocidal activity. We tested the interactions of MB with a number of trypanosomatid-specific molecules of the antioxidant metabolism. At pH 7, trypanothione and other (di)thiols were oxidized to disulfides by the phenothiazine drug. MB inhibited Trypanosoma cruzi trypanothione reductase (TR) (K(i)=1.9 microM), and served as a significant subversive substrate of this enzyme (K(M)=30 microM, k(cat)=4.9s(-1)). With lipoamide dehydrogenase, the second thiol-generating flavoenzyme of T. cruzi, the catalytic efficiency for MB reduction was found to be almost 10(6)M(-1)s(-1). When the system MB-enzyme-molecular oxygen acts as a NAD(P)H-driven redox cycler, a reactive oxygen species, H(2)O(2) or superoxide, is produced in each cycle. Since MB is an affordable, available, and accessible drug it might be tested--alone or in drug combinations--against trypanosomatid-caused diseases of animal and man.
亚甲蓝（MB）已知具有杀锥虫活性。我们测试了MB与抗氧化代谢中一些锥虫特异性分子的相互作用。在pH 7时，锥虫硫醇和其他（二）硫醇被吩噻嗪药物氧化为二硫化物。MB抑制克氏锥虫锥虫硫醇还原酶（TR）（K（i）=1.9 microM），并作为该酶的重要颠覆性底物（K（M）=30 microM，k（cat）=4.9s（-1））。对于克氏锥虫的第二种产生硫醇的黄素酶硫辛酰胺脱氢酶，发现其还原MB的催化效率几乎为10（6）M（-1）s（-1）。当MB - 酶 - 分子氧系统作为NAD（P）H驱动的氧化还原循环器时，每个循环中会产生活性氧物种，H（2）O（2）或超氧化物。由于MB是一种价格低廉、可获得且易于获取的药物，因此可以单独或与其他药物联合测试其对动物和人类由锥虫引起的疾病的疗效。
