去氢枞酸异丙醇胺衍生物的合成及其细胞毒性评价  

Synthesis and Cytotoxicity Evaluation of Dehydroabietic Acid Derivatives Bearing Isopropanolamine Moieties

作　　者：许爱狄 吴亚菊 周小群 苏时娟 许传鑫 杨菲菲 李芳耀[1] Xu Aidi;Wu Yaju;Zhou Xiaoqun;Su Shijuan;Xu Chuanxin;Yang Feifei;Li Fangyao(Guangxi Key Laboratory of Drug Discovery and Optimization,Guangxi Engineering Research Center for Pharmaceutical Molecular Screening and Druggability Evaluation,Key Laboratory of Medical Biotechnology and Translational Medicine,School of Pharmacy,Guilin Medical University,Guilin,541199)

机构地区：[1]广西药物分子发现与成药性优化重点实验室,广西药物分子筛选与成药性评价工程研究中心,广西高校医药生物技术与转化医学重点实验室,桂林医学院药学院,桂林541199

出　　处：《化学通报》2024年第6期739-748,671,共11页Chemistry

基　　金：广西自然科学基金项目(2023GXNSFAA026277);桂林市科学研究与技术开发计划项目(20210227-1);广西林产化学与工程重点实验室开放课题(GXFK2202);广西药物分子发现与成药性优化重点实验室课题(GKLPMDDO-2023-B03);广西高等学校千名中青年骨干教师培育计划项目;桂林医学院硕士研究生科研项目(GYYK2023017);国家级大学生创新创业训练计划项目(202210601033,202310601037)资助。

摘　　要：为了寻找高效的抗肿瘤活性化合物,设计合成了一系列去氢枞酸异丙醇胺类化合物,利用IR、NMR和MS对其结构进行表征。采用噻唑蓝(MTT)法评价了目标化合物对四种不同肿瘤细胞(人膀胱移行癌细胞(T24)、人肝癌细胞(HepG2)、人卵巢癌细胞(SK-OV-3)、人肺癌细胞(A549))和人正常肝细胞(LO2)的抗增殖活性。结果表明,部分化合物对肿瘤细胞的抑制作用优于阳性对照顺铂。其中,化合物3d对四种细胞株表现出最好的抗增殖效果,IC_(50)值分为8.10±0.28、8.65±0.10、13.21±0.35和8.24±0.42μmol/L。初步机理研究表明,化合物3d使A549细胞周期阻滞在G1/G0期,并诱导A549细胞凋亡,且呈浓度依赖性。With the expectation to search for effective anti-tumor agents,a serious of novel dehydroabietic acid derivatives containing isopropanolamine fragments were designed and synthesized,and their structures were characterized by IR,NMR,and MS.In addition,the antiproliferative activities against four different human cancer cell lines,T24(human bladder transitional cancer cells),HepG2(human liver cancer cells),SK-OV-3(human ovarian cancer cells),A549(human lung cancer cells)and human normal liver cell LO2 were evaluated using methyl thiazolyl tetrazolium(MTT)assay.The results demonstrated that some derivatives have a better inhibitory effect on tumor cells than the positive control cisplatin.Noticeably,compound 3d exhibited excellent anti-proliferation against the four cell lines with IC50 of 8.10±0.28μmol·L^(-1)(T24),8.65±0.10μmol·L^(-1)(HepG2),13.21±0.35μmol·L^(-1)(SK-OV-3)and 8.24±0.42μmol·L^(-1)(A549).The preliminary mechanism studies indicated that compound 3d block the cell cycle of A549 cancer cells in the G1/G0 phase and induces apoptosis in a concentration dependent manne.

关 键 词：去氢枞酸 异丙醇胺 抗肿瘤 细胞周期 细胞凋亡 

分 类 号：R914.5[医药卫生—药物化学]