6种黄槿倍半萜类成分的衍生化改造和体外抗肿瘤活性研究  

Modify and in vitro antitumor activity evaluation of six sesquiterpenoid components derivatives from Hibiscus tiliaceus

作　　者：王灿红 孙照翠 马国需[2] 魏建和[1,2] 陈德力[1] WANG Can-hong;SUN Zhao-cui;MA Guo-xu;WEI Jian-he;CHEN De-li(Hainan Provincial Key Laboratory of Resources Conservation and Development of Southern Medicine,Hainan Branch Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences&Peking Union Medical College,Haikou 570311,China;Institute of Medicinal Plant Development,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100193,China)

机构地区：[1]中国医学科学院,北京协和医学院药用植物研究所海南分所,海南省南药资源保护与开发重点实验室,海南海口570311 [2]中国医学科学院,北京协和医学院药用植物研究所,北京100193

出　　处：《现代药物与临床》2022年第3期445-452,共8页Drugs & Clinic

基　　金：海南省自然科学基金面上项目(219MS101);中国医学科学院医学与健康科技创新工程(重大协同创新项目)(2021-I2M-1-032)。

摘　　要：目的 对黄槿中6种天然倍半萜类成分进行衍生化改造,并对所得衍生物进行体外抗肿瘤活性评价,分析其构效关系。方法 选取各种芳胺对黄槿中发现的6种倍半萜成分进行席夫碱修饰,采用噻唑蓝(MTT)法考察合成的目标化合物对HeLa、HepG2和MCG-803细胞的体外抗增殖活性。结果 衍生改造了19个不同的倍半萜类衍生物,结合1H-NMR、13C-NMR、HR-MS确定其结构,其中17个衍生物首次得到。部分衍生物表现出良好的抗肿瘤活性,苄胺基团对此类骨架化合物的结构修饰能够较好地提高其抗肿瘤活性。结论 部分衍生物表现出良好的抗肿瘤活性,特别对HepG2细胞活性有较大的提高,化合物12、22、23具有进一步研究价值。Objective To modify derivatives of 6 natural sesquiterpenoids from Hibiscus tiliaceus Linn., evaluate their in vitro antitumor activities, and reveal the structure-activity relationship. Methods A series of amines from H. tiliaceus were used to synthesize the gossypol Schiff base of the 6 sesquiterpenoids. Their antitumor activities in vitro were evaluated for HeLa, HepG2, and MCG-803 by MTT assay. Results Nineteen derivatives were synthesized, seventeen of which was reported for the first time, and their structures were characterized by 1 H-NMR, 13 C-NMR, and HR-MS. MTT assay showed some sesquiterpenoid derivatives exhibited good antitumor activity against HeLa, HepG2, and MCG-803 cell, and benzylamine modification could enhance antitumor activity of these sesquiterpenoid skeletons. Conclusion Some derivatives show promising antitumor activities, especially for the HepG2 cell lines, and compound 12, 22, and 23 are worth further studying.

关 键 词：黄槿 倍半萜 衍生化 抗肿瘤 构效关系 

分 类 号：R284.2[医药卫生—中药学] R966[医药卫生—中医学]