通过SRC设计,合成 (±) -Millpuline A,并通过SRC对肺细胞保护作用进行生物评估
Heng Zhang1, Xiao Guo1, Di Zhou1
1School of Traditional Chinese Materia Medica Key Laboratory of Innovative Traditional Chinese Medicine for Major Chronic Diseases of Liaoning province Key Laboratory for TCM Material Basis Study and Innovative Drug Development of Shenyang City, Shenyang Pharmaceutical University, Shenyang, 110016, P.R. China.
ChemMedChem
|September 13, 2023
概括
研究人员开发了一种新的可见光反应来合成黄类药物,揭示了 (±) -millpuline A.
科学领域:
- 有机化学 有机化学
- 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:
- (±) - 密尔普林A的总合成面临挑战,包括低产量和未定义的生物活性.
- 基于黄类化合物的化合物因其潜在的治疗性质而引起人们的兴趣.
研究的目的:
- 开发一种可见光诱导的新型分子间 [2+2] 光环添加反应,用于类化合物合成.
- 为了合成和评估 (±) -millpuline A的生物活性衍生物.
- 为了阐明作用机制,并确定 (±) -millpuline A的肺部保护作用的分子点.
主要方法:
- 可见光诱导的分子间 [2+2] 光环添加反应.
- 20种黄类衍生物的合成和生物活性评估.
- 在MLE-12细胞中预测目标和实验验证.
- RT-Q-PCR和HTRF测试用于研究SRC活动.
主要成果:
- 建立了类素的新型合成途径,产生了20种衍生物.
- (±) -millpuline A和化合物B13a已经证明了对NNK的肺细胞保护作用.
- 循环butan部分的立体配置对于保护作用至关重要.
- SRC被确定为目标,其中 (±) -millpuline A抑制了SRC活动的转录.
结论:
- 这项研究提供了一种高效的合成复杂黄酸盐的方法.
- (±) -millpuline A通过调节SRC活性,对NNK诱导的肺损伤表现出保护作用.
- 这项工作为开发新的基于黄类药物的治疗方法和理解其机制奠定了基础.
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