芳苄叉基熊果酸硝酸酯类的合成及体外抗肿瘤活性评价  

Synthesis,Anti-tumor Activity in Vitro of Arylidene Ursolic Acid Nitrates

作　　者：朱祖昌 周慧娴 张特 何宝恩 胡庆忠 王涛[1] ZHU Zu-chang;ZHOU Hui-xian;ZHANG Te;HE Bao-en;HU Qing-zhong;WANG Tao(School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangzhou 510006,China;Technology Department,Shanghai SynTheAll Pharmaceutical Co.,Ltd.,Shanghai 200131,China;Purification Research and Development Center,Zhuhai United Laboratories Co.,Ltd.,Zhuhai 519040,China)

机构地区：[1]广州中医药大学中药学院,广州510006 [2]上海合全药业有限公司技术部,上海200131 [3]珠海联邦制药有限公司纯化研发中心,广东珠海519040

出　　处：《中国药学杂志》2022年第22期1895-1900,共6页Chinese Pharmaceutical Journal

基　　金：广州中医药大学“双一流”与高水平大学学科协同创新团队项目资助(2021xk87)。

摘　　要：目的为提高熊果酸的抗肿瘤活性及开发抗肿瘤新药,以熊果酸为先导物开展结构修饰和体外抗肿瘤活性评价。方法在熊果酸C2、C3和C28位进行结构修饰获得其芳苄叉基硝酸酯类衍生物,并运用四甲基偶氮唑蓝(MTT)法测定衍生物对5种人源肿瘤细胞(肝癌HepG-2细胞、乳腺癌MCF-7细胞、肺癌A549细胞、结肠癌HT-29细胞和宫颈癌Hela细胞)的体外抗肿瘤活性。结果对6个新型芳苄叉基熊果酸硝酸酯类衍生物的结构进行了红外、核磁共振光谱及质谱确证;MTT结果显示衍生物6c对MCF-7细胞的最大半数抑制浓度为(14.48±0.44)μmol·L^(-1),优于阳性药物顺铂[IC_(50)=(23.06±0.12)μmol·L^(-1)]。结论衍生物6c具有较强的抑制乳腺癌细胞增殖能力,值得深入研究。OBJECTIVE To carry out structure modification of ursolic acid and in vitro anti-tumor activity evaluation to improve the anti-tumor activity of ursolic acid and develop new anti-tumor drugs.METHODS Structural modification at positions C2,C3 and C28 of ursolic acid was performed to obtain arylidene ursolic acid drivatives.The inhibitory effects of arylidene ursolic acid drivatives on the proliferation of five human tumor cell lines(HepG2,MCF-7,A549,HT-29 and Hela)in vitro were detected by MTT assay.RESULTS The structures of six novel arylidene ursolic acid nitrates were confirmed by IR,^(1)H-NMR,^(13)C-NMR,and HR MS.The MTT assay results showed that the IC_(50)of derivative 6 c on MCF-7 cells was(14.48±0.44)μmol·L^(-1),6 c showed higher anti-proliferative activity than cisplatin[IC_(50)=(23.06±0.12)μmol·L^(-1)].CONCLUSION Derivative 6 c has strong anti-proliferation ability on MCF-7 tumor cells and is worthy of further investigation.

关 键 词：芳苄叉基熊果酸硝酸酯 MCF-7细胞 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]