Anti-HCV bioactivity of pseudoguaianolides from Parthenium hispitum
Anti-HCV bioactivity of pseudoguaianolides from Parthenium hispitum
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DOI：
10.1021/np060567e
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发表时间：
2007-04-01
影响因子：
5.1
通讯作者：
Eldridge, Gary R.
中科院分区：
文献类型：
--
作者：
Hu, Jin-Feng;Patel, Rupal;Eldridge, Gary R.
通过高通量天然产物化学方法，从硬毛豆中分离得到5个新的(1-5)和4个已知的(6-9)C-14-氧代1α-羟基-11(13)-伪愈创-6β，12-内酯，它们对丙型肝炎病毒的复制有很强的抑制作用。用半制备高效液相色谱系统对这些化合物进行了纯化。对于质量受限的样品，主要利用毛细管规模的核磁共振探针进行结构的小型化、阐明和去复制。化合物2-4在含有荧光素酶报告的亚基因组丙型肝炎病毒复制子系统中具有体外抗丙型肝炎病毒的活性，在2mM浓度下对丙型肝炎病毒的抑制率达90%以上。
Five new (1-5) and four known (6-9) C-14-oxygenated 1 alpha-hydroxy-11(13)-pseudoguaien-6 beta,12-olides with potent inhibition of hepatitis C virus (HCV) replication were obtained from Parthenium hispitum via high-throughput natural product chemistry methods. A semipreparative HPLC system was used to purify these compounds. The miniaturization of the structure elucidation and dereplication for the mass-limited samples were performed primarily utilizing a capillary-scale NMR probe. Compounds 2-4 were found to possess in vitro anti-HCV activity in the subgenomic HCV replicon system containing luciferase reporter with significant inhibition above 90% at 2 mu M concentration.