Pseudoamaolides A-O, anti-inflammatory triterpene spiroketal lactones from seeds of Pseudolarix amabilis

IF 4.5 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Bioorganic Chemistry Pub Date : 2022-12-01 DOI:10.1016/j.bioorg.2022.106180

Yuxun Zhu, Shangyi Wang, Zhaoxin Zhang, Huanping Zhang, Lisha Chai, Guosheng Liu, Chengshuo Yang, Haijing Zhang, Lianqiu Wu, Yong Li

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Abstract

Fifteen new triterpenoids (1–15), along with twenty known ones (16–35), were isolated from Pseudolarix amabilis. The triterpenoid structures include multiple skeleton types, such as 2,3-seco-cycloartane, 3,4-seco-cycloartane, 3,4:9,10-diseco-cycloartane, and 3,4:8,9:9,10-triseco-cycloartane, as elucidated by extensive spectroscopy (1D NMR, 2D NMR, HRESIMS, and IR) and single-crystal X-ray diffraction. The anti-inflammatory activities of compounds 1–35 were evaluated. Compounds 3, 11, 16, 24, 25, and 26 suppressed the transcription of the NF-κB-dependent reporter gene in LPS-induced 293T/NF-κB-Luc cells with IC₅₀ values of 0.12, 0.10, 0.30, 0.09, 0.49, and 0.35 μM, respectively. In addition, compound 16 showed anti-inflammatory activity against xylene-induced ear swelling in vivo with an inhibition rate of 44.7 % (30 mg/kg). Compound 16 significantly improved the disease activity index (DAI) of ulcerative colitis at a dose of 400 mg/kg in a dextran sodium sulfate (DSS)-induced mouse model of experimental ulcerative colitis (P < 0.01).

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伪马芦内酯A-O，抗炎的三萜螺旋酮内酯

从阿马利假螺旋藻中分离到了15个新的三萜(1 ~ 15)和20个已知的三萜(16 ~ 35)。通过广泛的光谱分析(1D NMR、2D NMR、hresms和IR)和单晶x射线衍射证实，三萜结构包括2,3-二叔环ar烷、3,4-二叔环ar烷、3,4:9,10-二叔环ar烷和3,4:8,9:9,10-三叔环ar烷等多种骨架类型。评价了化合物1 ~ 35的抗炎活性。化合物3、11、16、24、25和26在lps诱导的293T/NF-κB-Luc细胞中抑制NF-κ b依赖性报告基因的转录，IC50值分别为0.12、0.10、0.30、0.09、0.49和0.35 μM。此外，化合物16对二甲苯诱导的耳肿胀具有抗炎活性，抑制率为44.7% (30 mg/kg)。在葡聚糖硫酸钠(DSS)诱导的实验性溃疡性结肠炎小鼠模型中，400 mg/kg剂量的化合物16可显著改善溃疡性结肠炎的疾病活动指数(DAI)。0.01)。

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来源期刊

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.