Division of Applied Life Science (BK21 Program), IALS, Gyeongsang National University, Jinju 660-701, Republic of Korea.
Food Chem Toxicol. 2011 Aug;49(8):1849-56. doi: 10.1016/j.fct.2011.04.038. Epub 2011 May 6.
Neuraminidase is a proven target in anti-viral drug development. It also appears to be important for infection by certain pathogenic bacteria and has been implicated in biofilm formation. Based on activity-guided fractionation, the acetone extract of Amorpha fruticosa roots gave four flavanones 1-4 and three rotenoids 5-7 which were identified as amoradicin (1), amorisin (2), isoamoritin (3), amoricin (4), amorphigeni (5), dalbinol (6), and 6-ketodehydroamorphigenin (7), respectively. All isolated inhibitors showed strong neuraminidase inhibition with IC₅₀s between 0.12 and 22.03 μM. In particular, amorisin 2 exhibited 120 nM IC(₅₀, which is 30-fold more potent than the positive control, quercetin. In addition, this is the first report detailing rotenoids (IC₅₀ = 8.34-16.74 μM) exhibiting neuraminidase inhibition. Kinetic analysis revealed that all inhibitors were noncompetitive. The most active neuraminidase inhibitors (2, 3, 5, 6) were proven to be present in the native root in high quantities by HPLC. Finally, at concentrations where no toxicity was observed, 3 and 6 inhibited Pseudomonas aeruginosa biofilm production. 29.7% and 21.0% inhibition respectively was observed at 25 μΜ.
神经氨酸酶是抗病毒药物开发的既定靶点。它似乎对某些致病性细菌的感染也很重要，并与生物膜形成有关。基于活性导向的分离，紫穗槐根的丙酮提取物得到了四个黄烷酮 1-4 和三个鱼藤酮 5-7，分别鉴定为美洲槐素（1）、美洲槐定（2）、异美迪定（3）、美迪定（4）、美迪辛（5）、dalbinol（6）和 6-去氢美迪辛（7）。所有分离得到的抑制剂均表现出强烈的神经氨酸酶抑制活性，IC₅₀ 在 0.12 和 22.03 μM 之间。特别是美洲槐定 2 的 IC₅₀ 为 120 nM，比阳性对照槲皮素强 30 倍。此外，这是首次详细报道鱼藤酮（IC₅₀ = 8.34-16.74 μM）具有神经氨酸酶抑制作用。动力学分析表明，所有抑制剂均为非竞争性。通过 HPLC 证明，最有效的神经氨酸酶抑制剂（2、3、5、6）在天然根中以高浓度存在。最后，在没有观察到毒性的浓度下，3 和 6 抑制铜绿假单胞菌生物膜的产生。在 25 μM 时，分别观察到 29.7%和 21.0%的抑制作用。
