在C24位点修改的莫格罗尔衍生物的合成和抗炎活性
Jing-Ru Song1, Yu-Lu Wei1, Xiao-Hua Jiang1
1Guangxi Key Laboratory of Plant Functional Phytochemicals and Sustainable Utilization, Guangxi Institute of Botany, Guangxi Zhuang Autonomous Region and Chinese Academy of Sciences, Guilin, China.
莫格罗尔衍生物,特别是带有醇基因的B5化合物,通过抑制氧化和关键炎症介质,显示出增强的抗炎作用. 这表明开发新的抗炎药物是一个有前途的战略.
科学领域:
- 自然产品化学 自然产品化学
- 药用化学 医学化学
- 药理学 药理学是指药理学的学科.
背景情况:
- 莫格罗尔是莫格罗西德的聚糖体,具有固有的抗炎性质.
- 开发新的抗炎药物对于管理炎症性疾病至关重要.
研究的目的:
- 设计和合成新的mogrol衍生物.
- 评估这些衍生物在RAW264.7细胞中对脂聚糖 (LPS) 诱导的炎症的抗炎潜力.
主要方法:
- 合成了42种摩格罗尔衍生物,在C24位点进行了修改.
- 通过测量氧化 (NO) 生产来选抗炎活性.
- 评估抑制炎症媒介 (TNF-α,IL-6) 和蛋白质表达 (TLR4,p-p65,iNOS) 的情况.
- 分子对接模拟以预测与iNOS的结合相互作用.
主要成果:
- 大多数合成衍生品与莫格罗尔相比,在不表现出细胞毒性的情况下,表现出比莫格罗尔更好的NO生产抑制.
- 化合物B5,具有醇部分,显著抑制了TNF-α和IL-6分泌.
- 化合物B5有效抑制了TLR4,p-p65和iNOS蛋白的表达.
- 分子对接显示了B5与iNOS (-12.1 kcal/mol) 通过疏水和π-π相互作用具有强烈的结合亲和力.
结论:
- 莫格罗尔衍生物B5是一种强大的抗炎药物.
- 将一个内醇骨架混合到mogrol结构上是开发新型抗炎化合物的可行策略.
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