School of Biological Science and Technology, University of Jinan, Jinan, 250022, China.
Arch Pharm Res. 2022 May;45(5):328-339. doi: 10.1007/s12272-022-01383-5. Epub 2022 Apr 27.
One new clerodane-type furanoditerpenoid tinosinoid A (1) and nine new nor-clerodane analogs tinosinoids B-J (2-10) have been isolated from the stems of Tinospora sinensis. The structures of the new compounds with absolute configurations have been elucidated by spectroscopic means, including MS, NMR and ECD techniques, as well as chemical correlation. Compound 1 is a rare sulfur-containing clerodane diterpenoid incorporating a 2-mercaptoethanol unit via a thioether bond, while compounds 4/5 and 9 represent two pairs of unusual equilibrium regioisomers through an interesting intramolecular transesterification. Our bioassays established that 1 and 8 displayed moderate antiproliferative effects against two human tumor cell lines, and 9 and 10 showed significant α-glucosidase inhibitory activities. A kinetics study revealed that compound 10 was a noncompetitive α-glucosidase inhibitor, and its possible binding mode to the enzyme was further probed by molecular docking experiments.
从三叶崖爬藤的茎中分离得到了一个新的 clerodane 型呋喃型倍半萜 tinosinoid A（1）和九个新的 nor-clerodane 类似物 tinosinoids B-J（2-10）。通过包括 MS、NMR 和 ECD 技术以及化学相关在内的光谱方法阐明了具有绝对构型的新化合物的结构。化合物 1 是一种罕见的含硫 clerodane 二萜，通过硫醚键结合了 2-巯基乙醇单元，而化合物 4/5 和 9 则代表了两对通过有趣的分子内酯交换形成的不寻常的平衡区域异构体。我们的生物测定表明，1 和 8 对两种人肿瘤细胞系表现出中等的抗增殖作用，而 9 和 10 对 α-葡萄糖苷酶表现出显著的抑制活性。动力学研究表明，化合物 10 是一种非竞争性的 α-葡萄糖苷酶抑制剂，通过分子对接实验进一步探讨了其与酶的可能结合模式。
