Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, Yunnan 650091, People's Republic of China.
Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education and Yunnan Province, School of Chemical Science and Technology, Yunnan University, Kunming, Yunnan 650091, People's Republic of China.
Bioorg Chem. 2020 Dec;105:104363. doi: 10.1016/j.bioorg.2020.104363. Epub 2020 Oct 10.
Twenty-four new limonoids, toonaolides A-X (1-24), characterized with an α,β-unsaturated-γ-lactone A-ring were isolated from the twigs of Toona ciliata. Their structures and absolute configurations were elucidated by spectroscopic data, X-ray diffraction crystallography, and quantum chemistry calculations. Most of the isolated compounds (except 9, 18, and 24 which possessed the maleimide ring) featured the rare 21-hydroxybutenolide or 23-hydroxybutenolide moieties. In particular, compound 1 has an unprecedented limonoid architecture with 6/6 cis-fused A/B ring system and 2 has an unusual tetrahydrofuran ring B skeleton, featuring a 7/5/6/5 ring system. The biological evaluation showed that compounds 9, 11, 12, 14, and 18 exhibited significantly anti-NLRP3 inflammasome activity with IC values ranging from 3.2 to 9.7 μM. Analysis of IL-1β and caspase-1 expression revealed that compounds 11 and 12 are selective inhibitors of NLRP3 inflammasome, which could ameliorate cell pyroptosis by blocking NLRP3 inflammasome activation.
从香椿的嫩枝中分离得到了 24 种新的柠檬苦素类化合物，包括 1-24，其特征在于具有α，β-不饱和-γ-内酯 A 环。通过光谱数据、X 射线衍射晶体学和量子化学计算阐明了它们的结构和绝对构型。大多数分离得到的化合物（除了 9、18 和 24 具有马来酰亚胺环）都具有罕见的 21-羟基丁烯内酯或 23-羟基丁烯内酯部分。特别是，化合物 1 具有前所未有的柠檬苦素结构，具有 6/6 顺式稠合的 A/B 环系统和 2 具有不寻常的四氢呋喃环 B 骨架，具有 7/5/6/5 环系统。生物评价表明，化合物 9、11、12、14 和 18 表现出显著的抗 NLRP3 炎性小体活性，IC 值范围为 3.2 至 9.7μM。IL-1β 和 caspase-1 表达分析表明，化合物 11 和 12 是 NLRP3 炎性小体的选择性抑制剂，可通过阻断 NLRP3 炎性小体激活来改善细胞焦亡。
