Antonelli Anthony C, Zhang Yu, Golub Lorne M, Johnson Francis, Simon Sanford R
Department of Pathology .
J Enzyme Inhib Med Chem. 2014 Oct;29(5):663-9. doi: 10.3109/14756366.2013.837901. Epub 2013 Oct 9.
Curcumin (diferuloylmethane), the active ingredient in the eastern spice turmeric (Curcuma longa), has been shown to inhibit the activities of numerous enzymes and signaling molecules involved in cancer, bacterial and viral infections and inflammatory diseases. We have investigated the inhibitory activities of curcumin and chemically modified curcumin (CMC) derivatives toward lethal factor (LF), the proteolytic component of anthrax toxin produced by the bacterium Bacillus anthracis. Curcumin (Compound 1) appears to inhibit the catalytic activity of LF through a mixture of inhibitory mechanisms, without significant compromise to the binding of oligopeptide substrates, and one CMC derivative in particular, Compound 3 (4-phenylaminocarbonylbis-demethoxycurcumin), is capable of inhibiting LF with potency comparable with the parent compound, while also showing improved solubility and stability. The quantitative reduction in catalytic activity achieved by the different CMC derivatives appears to be a function of the proportion of the multiple mechanisms through which they inhibit the enzyme.
姜黄素（二阿魏酰甲烷）是东方香料姜黄（姜黄属植物）中的活性成分，已被证明能抑制多种参与癌症、细菌和病毒感染以及炎症性疾病的酶和信号分子的活性。我们研究了姜黄素和化学修饰的姜黄素（CMC）衍生物对致死因子（LF）的抑制活性，致死因子是炭疽杆菌产生的炭疽毒素的蛋白水解成分。姜黄素（化合物1）似乎通过多种抑制机制的组合来抑制LF的催化活性，而对寡肽底物的结合没有显著影响，特别是一种CMC衍生物，化合物3（4-苯基氨基羰基双脱甲氧基姜黄素），能够以与母体化合物相当的效力抑制LF，同时还表现出改善的溶解性和稳定性。不同CMC衍生物实现的催化活性的定量降低似乎是它们抑制该酶的多种机制比例的函数。
