荧光23-羟基白桦酸探针的合成、生物学评价及其细胞定位研究。
Synthesis, Biological Evaluation of Fluorescent 23-Hydroxybetulinic Acid Probes, and Their Cellular Localization Studies.
作者信息
Yao Hong, Wei Guoxiang, Liu Yanpeng, Yao Hequan, Zhu Zheying, Ye Wencai, Wu Xiaoming, Xu Jinyi, Xu Shengtao
机构信息
Department of Medicinal Chemistry and State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
Division of Molecular Therapeutics & Formulation, School of Pharmacy, The University of Nottingham, University Park Campus, Nottingham NG7 2RD, U.K.
出版信息
ACS Med Chem Lett. 2018 Sep 25;9(10):1030-1034. doi: 10.1021/acsmedchemlett.8b00321. eCollection 2018 Oct 11.
23-Hydroxybetulinic acid (23-HBA) is a complex lupane triterpenoid, which has attracted increasing attention as an anticancer agent. However, its detailed mechanism of anticancer action remains elusive so far. To reveal its anticancer mode of action, a series of fluorescent 23-HBA derivatives conjugated with coumarin dyes were designed, synthesized, and evaluated for their antiproliferative activities. Subcellular localization and uptake profile studies of representative fluorescent 23-HBA probe were performed in B16F10 cells, and the results suggested that probe was rapidly taken up into B10F10 cells in a dose-dependent manner and mitochondrion was the main site of its accumulation. Further mode of action studies implied that the mitochondrial pathway was involved in 23-HBA-mediated apoptosis. Together, our results provided new clues for revealing the molecular mechanism of natural product 23-HBA for its further development into an antitumor agent.
23-羟基桦木酸（23-HBA）是一种复杂的羽扇烷三萜类化合物，作为一种抗癌剂已引起越来越多的关注。然而，其详细的抗癌作用机制迄今仍不清楚。为了揭示其抗癌作用方式，设计、合成了一系列与香豆素染料共轭的荧光23-HBA衍生物，并对其抗增殖活性进行了评估。在B16F10细胞中对代表性荧光23-HBA探针进行了亚细胞定位和摄取情况研究，结果表明探针以剂量依赖的方式迅速被B10F10细胞摄取，线粒体是其主要蓄积部位。进一步的作用方式研究表明，线粒体途径参与了23-HBA介导的细胞凋亡。总之，我们的结果为揭示天然产物23-HBA的分子机制提供了新线索，以便将其进一步开发成一种抗肿瘤药物。
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