来自Alternaria物种的烯基的结构阐明和生物活动
Anna Kiefer1, Marcel Arnholdt1, Viktoria Grimm1
1Molecular Biotechnology & Systems Biology, RPTU, Paul-Ehrlich-Straße 23, D-67663, Kaiserslautern, Germany.
Mycotoxin research
|June 23, 2023
概括
研究人员发现了新的真菌化合物,可以调节KEAP1-Nrf2/ARE通路,这是氧化应激的关键调节者. 一些化合物显示出对抗炎症疾病和癌症的治疗开发潜力.
科学领域:
- 生物化学 生物化学
- 自然产品化学 自然产品化学
- 细胞生物学 细胞生物学
背景情况:
- KEAP1-Nrf2/ARE通路对于细胞防御氧化应激至关重要.
- 这种途径的失调与炎症性疾病和癌症有关.
- 针对这种途径为与氧化应激相关的病理提供了治疗潜力.
研究的目的:
- 为了确定调节Nrf2/ARE通路的新型真菌二次代谢物.
- 评估这些化合物的生物活性,包括细胞毒性和对氧化应激标志物的影响.
主要方法:
- 使用NMR光谱学和质谱学对真菌代谢物的隔离和结构阐明.
- 在BEAS-2B细胞中使用光酶记者对Nrf2/ARE依赖基因表达的测定.
- 单独化合物的细胞毒性 (LC50值) 和氧化作用的评估.
主要成果:
- 从一种Alternaria物种中分离出了三种新的烯基和变毒素-I (ATX-I).
- 化合物1和ATX-I表现出显著的细胞毒性,并诱导了ARE-依赖的光酶表达.
- 化合物1和ATX-I上调了血红素酶-1,而化合物3调节了sod3mRNA水平.
结论:
- 来自*Alternaria*物种的新型烯基可以调节KEAP1-Nrf2/ARE通路.
- 化合物1和ATX-I显示出该途径的强烈激活和氧化作用.
- 化合物3表现出明显的活性,表明氧化应激反应的差异调节.
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