González-Garza M T, Matlin S A, Mata-Cárdenas B D, Said-Fernández S
Unidad de Investigación Biomédica del Noreste, Instituto Mexicano del Seguro Social, Monterrey, N. L.
Arch Med Res. 1993 Summer;24(2):183-7.
Gossypol, a natural racemic mixture with action on NADP- and NAD-oxidoreductases from diverse species, has been proposed as a possible antiamebic medication considering several of its pharmacological properties. In this study it was found that malic enzyme and alcohol dehydrogenase from Entamoeba histolytica are strongly inhibited by (+/-)-gossypol, and both (+)- and (-)- enantiomers. The inhibition was of the noncompetitive type among their respective substrates in all cases. The (+/-), (+)-, (-)-gossypol half-maximal inhibitory concentrations (IC50) for the malic enzyme were 3.71, 13.37 and 1.03 microM, and against the alcohol dehydrogenase 79.64, 124.43 and 42.56 microM, respectively. Therefore, the (-) enantiomer resulted 3.6 and 13.0 times more potent than the racemic mixture and (+)-gossypol, respectively, to inhibit the malic enzyme, and 1.9 times and 2.9 times more potent than the racemic mixture and (+)-gossypol, respectively, against the alcohol dehydrogenase. Accordingly, one possible mechanism of the antiamebic effect of gossypol could be the inhibition of vital NADP-dependent enzymes as those analyzed in this study.
棉酚是一种天然的外消旋混合物，对来自不同物种的NADP和NAD氧化还原酶有作用，鉴于其多种药理特性，已被提议作为一种可能的抗阿米巴药物。在本研究中发现，溶组织内阿米巴的苹果酸酶和乙醇脱氢酶受到（±）-棉酚以及（+）-和（-）-对映体的强烈抑制。在所有情况下，其抑制作用在各自底物之间均为非竞争性类型。（±）-、（+）-、（-）-棉酚对苹果酸酶的半数最大抑制浓度（IC50）分别为3.71、13.37和1.03微摩尔，对乙醇脱氢酶的IC50分别为79.64、124.43和42.56微摩尔。因此，（-）对映体抑制苹果酸酶的效力分别比外消旋混合物和（+）-棉酚高3.6倍和13.0倍，对乙醇脱氢酶的效力分别比外消旋混合物和（+）-棉酚高1.9倍和2.9倍。因此，棉酚抗阿米巴作用的一种可能机制可能是抑制本研究中分析的重要的NADP依赖性酶。
