香椿 A-I，香椿 M. Roem. 中具有 NLRP3 炎性体抑制活性的柠檬苦素。
Toonaones A-I, limonoids with NLRP3 inflammasome inhibitory activity from Toona ciliata M. Roem.
机构信息
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, 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, China.
出版信息
Phytochemistry. 2021 Apr;184:112661. doi: 10.1016/j.phytochem.2021.112661. Epub 2021 Jan 14.
Nine undescribed limonoids, 18(13 → 14)-abeo-15β,21-dihydroxy-24,25,26,27-tetranor-3,7-dioxoapotirucalla-1,9(11),13(17),20(22)-tetraen-23,21-olide (Toonaone A), 21-hydroxy-24,25,26,27-tetranor-3,7,15-trioxoapotirucalla-1,9(11),20(22)-trien-23,21-olide (Toonaone B), 7α,21-dihydroxy-12α-isobutyryl-24,25,26,27-tetranor-3,15-dioxoapotirucalla-1,20(22)-dien-23,21-olide (Toonaone C), 7,8-seco-7-methyl ester-11β-acetoxy-14β,15β-epoxy-21-hydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,8(30),20(22)-trien-23,21-olide (Toonaone D), 7,8-seco-7-methyl ester-11β-acetoxy-14β,15β-epoxy-23-hydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,8(30),20(22)-trien-21,23-olide (Toonaone E), 7,8-seco-7-methyl ester-11β-acetoxy-14β,15β-epoxy-6β,21-dihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,8(30),20(22)-trien-23,21-olide (Toonaone F), 7,8-seco-7-methyl ester-14β,15β-epoxy-8α,21-dihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,20(22)-dien-23,21-olide (Toonaone G), 7,8-seco-7-methyl ester-14β,15β-epoxy-6β,8α,21-trihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,20(22)-dien-23,21-olide (Toonaone H), 7,8-seco-7-methyl ester-14β,15β-epoxy-6β,8α,21-trihydroxy-24,25,26,27-tetranor-3-oxoapotirucalla-1,20(22)-dien-21,23-diimide (Toonaone I), and five known analogues were isolated from the twigs of Toona ciliata M. Roem. (Meliaceae). Toonaone A possesses the first rare 18(13 → 14)-abeo-limonoid skeleton reported from the genus Toona. Their structures were elucidated using spectroscopic data analyses and quantum chemistry calculations. Biological evaluation showed that toonaone C, toonaone D, toonaone G, toonaciliatavarin F, and toonaciliatavarin G exhibited significant anti-NLRP3 inflammasome activity with IC values ranging from 3.74 to 18.7 μM. GMDMD, IL-1β, and caspase-1 analyses suggested that toonaone D inhibited NLRP3 inflammasome activation and blocked macrophage pyroptosis.
从楝科香椿属植物香椿（Toona ciliata M. Roem.）的嫩枝中分离得到 9 个新的柠檬苦素类化合物，分别鉴定为 18(13 → 14)-abeo-15β,21-二羟基-24,25,26,27-四去甲-3,7-二氧代阿波卡-1,9(11),13(17),20(22)-四烯-23,21-内酯（香椿酮 A）、21-羟基-24,25,26,27-四去甲-3,7,15-三氧代阿波卡-1,9(11),20(22)-三烯-23,21-内酯（香椿酮 B）、7α,21-二羟基-12α-异丁酰基-24,25,26,27-四去甲-3,15-二氧代阿波卡-1,20(22)-二烯-23,21-内酯（香椿酮 C）、7,8-裂环-7-甲酯基-11β-乙酰氧基-14β,15β-环氧-21-羟基-24,25,26,27-四去甲-3-氧代阿波卡-1,8(30),20(22)-三烯-23,21-内酯（香椿酮 D）、7,8-裂环-7-甲酯基-11β-乙酰氧基-14β,15β-环氧-23-羟基-24,25,26,27-四去甲-3-氧代阿波卡-1,8(30),20(22)-三烯-21,23-内酯（香椿酮 E）、7,8-裂环-7-甲酯基-11β-乙酰氧基-14β,15β-环氧-6β,21-二羟基-24,25,26,27-四去甲-3-氧代阿波卡-1,8(30),20(22)-三烯-23,21-内酯（香椿酮 F）、7,8-裂环-7-甲酯基-14β,15β-环氧-8α,21-二羟基-24,25,26,27-四去甲-3-氧代阿波卡-1,20(22)-二烯-23,21-内酯（香椿酮 G）、7,8-裂环-7-甲酯基-14β,15β-环氧-6β,8α,21-三羟基-24,25,26,27-四去甲-3-氧代阿波卡-1,20(22)-二烯-23,21-内酯（香椿酮 H）、7,8-裂环-7-甲酯基-14β,15β-环氧-6β,8α,21-三羟基-24,25,26,27-四去甲-3-氧代阿波卡-1,20(22)-二烯-21,23-二酰亚胺（香椿酮 I），以及 5 个已知的类似物。香椿酮 A 具有从香椿属植物中首次报道的罕见 18(13 → 14)-abeo-柠檬苦素骨架。通过光谱数据分析和量子化学计算确定了它们的结构。生物活性评价表明，香椿酮 C、香椿酮 D、香椿酮 G、香椿酮 F 和香椿酮 G 对 NLRP3 炎性小体具有显著的抑制作用，IC 值范围为 3.74-18.7 μM。GMDMD、IL-1β 和 caspase-1 分析表明，香椿酮 D 抑制 NLRP3 炎性小体激活并阻断巨噬细胞焦亡。
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