Division of Applied Life Science (BK21 program), IALS, Gyeongsang National University, Jinju 660-701, Republic of Korea.
Bioorg Med Chem. 2013 Jun 1;21(11):3051-7. doi: 10.1016/j.bmc.2013.03.027. Epub 2013 Mar 29.
SARS-CoV papain-like protease (PLpro) is an important antiviral target due to its key roles in SARS virus replication. The MeOH extracts of the fruits of the Paulownia tree yielded many small molecules capable of targeting PLpro. Five of these compounds were new geranylated flavonoids, tomentin A, tomentin B, tomentin C, tomentin D, tomentin E (1-5). Structure analysis of new compounds (1-5) by NMR showed that they all contain a 3,4-dihydro-2H-pyran moiety. This chemotype is very rare and is derived from cyclization of a geranyl group with a phenol functionality. Most compounds (1-12) inhibited PLpro in a dose dependent manner with IC50's raging between 5.0 and 14.4 μM. All new compounds having the dihydro-2H-pyran group showed better inhibition than their parent compounds (1 vs 11, 2 vs 9, 4 vs 12, 5 vs 6). In kinetic studies, 1-12 emerged to be reversible, mixed inhibitors.
严重急性呼吸综合征冠状病毒木瓜蛋白酶样蛋白酶（PLpro）是一种重要的抗病毒靶点，因为它在严重急性呼吸综合征病毒复制中起着关键作用。泡桐树果实的甲醇提取物产生了许多能够靶向 PLpro 的小分子。其中 5 种为新型香叶基化黄酮类化合物，绒毛桐素 A、绒毛桐素 B、绒毛桐素 C、绒毛桐素 D、绒毛桐素 E（1-5）。通过 NMR 对新化合物（1-5）的结构分析表明，它们都含有 3,4-二氢-2H-吡喃部分。这种化学型非常罕见，是香叶基与酚官能团环化而来的。大多数化合物（1-12）以剂量依赖的方式抑制 PLpro，IC50 范围在 5.0 到 14.4 μM 之间。所有具有二氢-2H-吡喃基团的新化合物的抑制作用均优于其母体化合物（1 对 11，2 对 9，4 对 12，5 对 6）。在动力学研究中，1-12 表现为可逆的混合抑制剂。
