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
许爱狄 1吴亚菊 1周小群 1苏时娟 1许传鑫 1杨菲菲 1李芳耀1
作者信息
- 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
- 折叠
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,IC50值分为8.10±0.28、8.65±0.10、13.21±0.35和8.24±0.42 μmol/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.
Abstract
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 1R,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 L02 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±0.28 μmol L-1(T24),8.65±0.10 µmol L-1(HepG2),13.21±0.35μmol·L-1(SK-OV-3)and 8.24±0.42 µmol 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Key words
Dehydroabietic acid/Isopropanolamine/Antitumor/Cell cycle/Apoptosis引用本文复制引用
基金项目
广西自然科学基金(2023GXNSFAA026277)
桂林市科学研究与技术开发计划(20210227-1)
广西林产化学与工程重点实验室开放基金(GXFK2202)
广西药物分子发现与成药性优化重点实验室项目(GKLPMDDO-2023-B03)
广西壮族自治区高等学校千名中青年骨干教师培育计划()
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(202210601033)
国家级大学生创新创业训练计划(202310601037)
出版年
2024
NETL
NSTL
万方数据