Division of Applied Life Science (BK21 plus), IALS, Graduate School of Gyeongsang National University, Jinju 660-701, Republic of Korea.
Bioorg Med Chem. 2013 Nov 1;21(21):6398-404. doi: 10.1016/j.bmc.2013.08.049. Epub 2013 Sep 3.
Bacterial neuraminidase (NA) is one of the key enzymes involved in pathogenesis of inflammation during infection. The organic extract of the roots of Flemingia philippinensis showed high bacterial NA inhibitory activity with an IC50 of around 5μg/mL. Activity-guided separation of the methanol extract yielded nine prenylated isoflavones together with the novel species isoflavone (2) which was given the name flemingsin. Isolated prenylated isoflavones (1-9) were evaluated for NA inhibition and their IC50 values were determined to range between 0.30 and 56.8μM. The most potent inhibitor 4 (IC50=300nM, Ki=130nM) features a catechol motif in the B-ring and a furan in the A-ring. Structure-activity analysis also showed a 4-hydroxyl group within the B-ring was essential for NA inhibitory activity, because isoflavone (9) having protected 4-hydroxyl group was much less potent than its hydroxylated counterpart. All neuraminidase compounds screened were found to be reversible noncompetitive inhibitors. Furthermore, the most active NA inhibitors (1-9) were proven to be present in the native roots in high quantities by HPLC and LC-DAD-ESI/MS.
细菌神经氨酸酶（NA）是感染过程中炎症发病机制中涉及的关键酶之一。 Flemingia philippinensis 根的有机提取物表现出高的细菌 NA 抑制活性，IC50 约为 5μg/mL。采用活性导向分离甲醇提取物得到了九个异戊烯基异黄酮，以及新型异黄酮（2），被命名为 Flemingsin。分离的异戊烯基异黄酮（1-9）被评估为 NA 抑制活性，其 IC50 值在 0.30 至 56.8μM 之间。最有效的抑制剂 4（IC50=300nM，Ki=130nM）在 B 环中具有儿茶酚基序，在 A 环中具有呋喃基。结构-活性分析还表明，B 环内的 4-羟基是 NA 抑制活性所必需的，因为具有保护 4-羟基的异黄酮（9）比其羟基化对应物的活性要低得多。筛选出的所有神经氨酸酶化合物均被发现为可逆的非竞争性抑制剂。此外，通过 HPLC 和 LC-DAD-ESI/MS 证明，最有效的 NA 抑制剂（1-9）在天然根中以高浓度存在。
