雷公藤中醌甲基三萜对 SARS-CoV 3CLpro 的抑制作用。
SARS-CoV 3CLpro inhibitory effects of quinone-methide triterpenes from Tripterygium regelii.
机构信息
Eco-Friendly Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, Republic of Korea.
出版信息
Bioorg Med Chem Lett. 2010 Mar 15;20(6):1873-6. doi: 10.1016/j.bmcl.2010.01.152. Epub 2010 Feb 4.
Quinone-methide triterpenes, celastrol (1), pristimerin (2), tingenone (3), and iguesterin (4) were isolated from Triterygium regelii and dihydrocelastrol (5) was synthesized by hydrogenation under palladium catalyst. Isolated quinone-methide triterpenes (1-4) and 5 were evaluated for SARS-CoV 3CL(pro) inhibitory activities and showed potent inhibitory activities with IC(50) values of 10.3, 5.5, 9.9, and 2.6 microM, respectively, whereas the corresponding 5 having phenol moiety was observed in low activity (IC(50)=21.7 microM). As a result, quinone-methide moiety in A-ring and more hydrophobic E-ring assist to exhibit potent activity. Also, all quinone-methide triterpenes 1-4 have proven to be competitive by the kinetic analysis.
从雷公藤中分离得到醌甲基三萜化合物 celastrol（1）、pristimerin（2）、tingenone（3）和 iguesterin（4），并在钯催化剂下氢化合成了二氢 celastrol（5）。对分离得到的醌甲基三萜化合物（1-4）和 5 进行了 SARS-CoV 3CL(pro)抑制活性评价，结果显示它们具有很强的抑制活性，IC50 值分别为 10.3、5.5、9.9 和 2.6 μM，而具有酚结构的相应化合物 5 的活性较低（IC50=21.7 μM）。因此，A 环中的醌甲基部分和更疏水的 E 环有助于表现出较强的活性。此外，动力学分析表明，所有醌甲基三萜化合物 1-4 均为竞争性抑制剂。
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