哈尔佩罗伊德A-F,来自Harrisonia perforata的复杂聚烯酸黄醇,通过准ABC载体功能来逆转多药性耐药性
Pei-Pei An1,2, Ying Li3, Jin-Hai Yu3
1State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, China.
The Journal of organic chemistry
|February 9, 2026
概括
六种新的花葡萄衍生物 (PPAP) 被从Harrisonia perforata中分离出来. 化合物3通过抑制ABCB1和ABCG2载体,增强了帕克利塔塞尔的疗效.
科学领域:
- 自然产品化学 自然产品化学
- 药理学 药理学是指药理学的学科.
- 药用化学 医学化学
背景情况:
- 黄醇衍生物 (PPAP) 已知具有多种生物活性.
- 穿孔 (Harrisonia perforata) 是一种具有潜在药用应用的植物物种.
研究的目的:
- 为了隔离和描述来自Harrisonia perforata的新型PPAP.
- 为了研究隔离化合物的抗癌辅助潜力.
主要方法:
- 基于LC/MS-MS的基于特征的分子网络 (FBMN) 用于化合物隔离.
- 综合光谱分析 (NMR,MS) 用于结构阐明.
- 在体外细胞毒性测定和药物相互作用研究.
- 分子对接模拟以了解结合机制.
主要成果:
- 确定了6种新的PPAP (1-6) 具有乙替代剂.
- 综合体1展示了一个独特的5/5/6/5环架构.
- 化合物5和6的特点是佐原核和基拉尼尔衍生的环醇单元.
- 化合物3没有表现出细胞毒性,但对HCT-15细胞的帕克利塔塞尔活性增强了42.8倍.
- 化合物3抑制了ABCB1和ABCG2转运器的功能,而没有改变它们的表达.
- 分子对接证实了化合物3与ABCB1和ABCG2的稳定结合.
结论:
- 在Harrisonia perforata.中发现了新的PPAP.
- 化合物3通过抑制药物流量载体,显示出作为抗癌辅助剂的潜力.
- 对化合物3的治疗应用进行进一步的研究是有必要的.
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