Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles (ICSN), CNRS, Labex LERMIT, 1, Avenue de la Terrasse, 91198 Gif sur Yvette Cedex, France.
J Nat Prod. 2012 Dec 28;75(12):2183-7. doi: 10.1021/np300637t. Epub 2012 Dec 7.
A chemical study of the Vietnamese plant species Trigonostemon howii led to the isolation of a new tigliane-type diterpenoid, trigowiin A (1), along with several known coumarins and phenylpropanoids. The planar structure and the relative configuration of compound 1 were elucidated based on spectroscopic analysis, including 1D- and 2D-NMR experiments, mass spectrometry, and comparison with literature data. Trigowiin A (1) exhibited moderate antiviral activity in a virus-cell-based assay for Chikungunya virus (CHIKV). Since the structure of compound 1 is closely related to those of well-known tigliane diterpenoids such as prostratin (2), phorbol (3), 12-O-tetradecanoylphorbol 13-acetate (TPA) (4), and 4α-TPA (5), the antiviral activity of the latter compounds was also evaluated against CHIKV, as well as in virus-cell-based assays of two additional members of the genus Alphavirus (Sindbis virus, SINV, and Semliki forest virus, SFV). Whereas prostratin inhibited CHIKV replication with a moderate EC(50) of 2.6 μM and a selectivity index (SI) approximating 30, compound 4 proved to be an extremely potent inhibitor, with an EC(50) of ∼3 nM and a SI near 2000. Interestingly, no or very little activity was observed on the replication of SINV and SFV.
对越南植物物种 Trigonostemon howii 的化学研究导致分离出一种新的丁香烷型二萜，即 trigowiin A（1），以及几种已知的香豆素和苯丙素。根据光谱分析，包括 1D 和 2D-NMR 实验、质谱和与文献数据的比较，确定了化合物 1 的平面结构和相对构型。trigowiin A（1）在基于病毒细胞的寨卡病毒（CHIKV）测定中表现出中等的抗病毒活性。由于化合物 1 的结构与已知的丁香烷二萜如 prostratin（2）、佛波醇（3）、12-O-十四烷酰佛波醇 13-乙酸酯（TPA）（4）和 4α-TPA（5）密切相关，因此还评估了后两种化合物对 CHIKV 的抗病毒活性，以及在 Sindbis 病毒（SINV）和 Semliki 森林病毒（SFV）两种属的另外两种成员的基于病毒细胞的测定中。虽然 prostratin 以接近 30 的选择性指数（SI）和中等的 EC（50）为 2.6 μM 抑制 CHIKV 复制，但化合物 4 被证明是一种极其有效的抑制剂，EC（50）约为 3 nM，SI 接近 2000。有趣的是，对 SINV 和 SFV 的复制没有或很少有活性。
