Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, Yunnan, P.R. China.
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, Yunnan, P.R. China.
Bioorg Chem. 2021 Oct;115:105178. doi: 10.1016/j.bioorg.2021.105178. Epub 2021 Jul 20.
Four undescribed ent-kaurane diterpenoids, wilkaunoids A - D (1-4), and three undescribed abietane diterpenoids, wilabinoids A - C (13-15), along with thirteen known ones (5-12 and 16-20), were isolated from Tripterygium wilfordii. Their structures were elucidated by extensive spectroscopic methods, electroniccirculardichroism calculation, and X-ray diffraction analysis. Compounds 1 and 2 were a pair of C-19 epimers of ent-kaurane diterpenoids, featuring a rare 19,20-epoxy-19,20-dimethoxy-kaurane fragment. Compound 3 possessed a rare naturally occurring 1,3-dioxacyclohexane moiety. Compounds 13 and 15 represented the first example of abietane diterpenoids with an isovalerate substitution from the genus of Tripterygium. The possible biosynthetic pathways of 1-3 were postulated. The effect of 1-20 on nitric oxide production was examined in lipopolysaccharide-stimulated RAW 264.7 cells. Abietane diterpenoid quinones 7-13 (IC: 1.9-10.2 μM) exhibited the significant activity to inhibit nitric oxide production versus positive control (NG-monomethyl-l-arginine acetate salt, IC = 24.9 μM). The structure activity relationship of 7-13 in inhibiting nitric oxide production was then discussed. The most potent 7 and 8 were found to significantly suppress the expression of cyclooxygenase-2 and inducible nitric oxide synthase proteins, showing a good anti-inflammatory potential. The findings provided some valuable insights for the discovery and structural modification of abietane diterpenoids towards anti-inflammatory lead compounds.
从雷公藤中分离得到了四个未描述的-ent-贝壳杉烷二萜，威尔考努oids A-D（1-4），和三个未描述的枞烷二萜，威尔阿宾oids A-C（13-15），以及十三个已知的化合物（5-12 和 16-20）。通过广泛的光谱方法、电子圆二色性计算和 X 射线衍射分析确定了它们的结构。化合物 1 和 2 是一对-ent-贝壳杉烷二萜的 C-19 差向异构体，具有罕见的 19,20-环氧-19,20-二甲氧基贝壳杉片段。化合物 3 具有罕见的天然存在的 1,3-二氧杂环己烷部分。化合物 13 和 15 代表了从雷公藤属中分离得到的第一个枞烷二萜类化合物，具有异戊酸取代基。提出了 1-3 的可能生物合成途径。在脂多糖刺激的 RAW 264.7 细胞中，检查了 1-20 对一氧化氮产生的影响。枞烷二萜醌 7-13（IC：1.9-10.2 μM）对抑制一氧化氮产生具有显著的活性，优于阳性对照（NG-单甲基-L-精氨酸醋酸盐，IC=24.9 μM）。然后讨论了 7-13 抑制一氧化氮产生的构效关系。发现最有效的 7 和 8 能够显著抑制环氧化酶-2 和诱导型一氧化氮合酶蛋白的表达，显示出良好的抗炎潜力。这些发现为枞烷二萜类化合物的抗炎先导化合物的发现和结构修饰提供了一些有价值的见解。
