Tan Xue Fei, Kim Dae Wook, Song Yeong Hun, Kim Jeong Yoon, Yuk Heung Joo, Wang Yan, Curtis-Long Marcus J, Park Ki Hun
a Division of Applied Life Science (BK21 Plus) , IALS, Gyeongsang National University , Jinju , Republic of Korea and.
b Department of Chemistry and Chemical Biology , Cornell University , Ithaca , NY , USA.
J Enzyme Inhib Med Chem. 2016;31(sup1):16-22. doi: 10.3109/14756366.2015.1118683. Epub 2016 Aug 25.
Campylotropis hirtella is used as a food supplement in the subtropical region of China. In an intensive hunt for human neutrophil elastase inhibitors, we isolated eight flavonoids from C. hirtella three of which (1-3) emerged to be elastase inhibitors. Geranylated flavonoids (1-3) displayed significant inhibitory activity with ICs between 8.5 and 30.8 μM. The most striking example was geranylated isofavanone 3 that inhibited elastase significantly (IC=30.8 μM) but its parent compound (dalbergioidin) and isoflavone analog (5) were inactive (IC>200 μM). Compounds (1-3) displayed different kinetic mechanisms (noncompetitive, competitive, and mixed type, respectively) that were dependent upon the parent skeleton. The competitive inhibitor, isoflavan-3-ol-4-one 2 manifested an inhibition of isomerization profile for elastase with kinetic parameters K=0.0386 MS, K=0.0244 μMS and K = 16.3427 μM. The specific identification of metabolites was accomplished by LC-DAD-ESI/MS that was also used to analyze abundance of active components (1-3) within the plant.
毛杭子梢在中国亚热带地区被用作食品补充剂。在对人中性粒细胞弹性蛋白酶抑制剂的深入搜寻中，我们从毛杭子梢中分离出了8种黄酮类化合物，其中3种（1 - 3）是弹性蛋白酶抑制剂。香叶基化黄酮类化合物（1 - 3）表现出显著的抑制活性，IC₅₀在8.5至30.8 μM之间。最显著的例子是香叶基化异黄烷酮3，它对弹性蛋白酶有显著抑制作用（IC₅₀ = 30.8 μM），但其母体化合物（黄檀素）和异黄酮类似物（5）无活性（IC₅₀ > 200 μM）。化合物（1 - 3）表现出不同的动力学机制（分别为非竞争性、竞争性和混合型），这取决于母体骨架。竞争性抑制剂异黄烷 - 3 - 醇 - 4 - 酮2对弹性蛋白酶的异构化过程有抑制作用，动力学参数为Kₘ = 0.0386 μM·s⁻¹，Kᵢ = 0.0244 μM·s⁻¹和Kₒ = 16.3427 μM。代谢物的具体鉴定通过LC - DAD - ESI/MS完成，该方法也用于分析植物中活性成分（1 - 3）的含量。
