文献类型：期刊文献

中文题名：N-杂环异海松酰基磺酰胺的制备及其抗肿瘤活性

英文题名：Synthesis and antitumor activity of isopimaric N-hetero-cyclic sulfonamides derivatives

作者：卢言菊[1,2] 赵振东[1,2] 毕良武[1,2] 陈玉湘[1,2] 王婧[1,2] 徐士超[1,2]

第一作者：卢言菊

通信作者：Chen, Yuxiang

机构：[1]中国林业科学研究院林产化学工业研究所生物质化学利用国家工程实验室国家林业局林产化学工程重点开放性实验室江苏省生物质能源与材料重点实验室南京林业大学林业资源高效加工利用协同创新中心,江苏南京210042;[2]中国林业科学研究院林业新技术研究所,北京100091

年份：2021

卷号：38

期号：3

起止页码：578-584

中文期刊名：精细化工

外文期刊名：Fine Chemicals

收录：CSTPCD;;EI(收录号：20211410179194);Scopus;北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：国家自然科学基金(31700504);江苏省生物质能源与材料重点实验室基本科研业务费基金(JSBEM-201808)。

语种：中文

中文关键词：异海松酸;杂环磺酰胺;合成;表征;抗肿瘤活性;医药原料

外文关键词：isopimaric acid;heterocyclic sulfonamide;synthesis;characterization;antitumor activity;drug materials

分类号：TQ463

摘要：为了寻求以天然资源为原料的抗肿瘤药物,以异海松酸为原料,设计并合成了6个N-[4-(异海松酰胺基)苯基]-杂环磺酰胺类化合物(Ⅴa~Ⅴf),采用FTIR、^(1)HNMR、^(13)CNMR和MS对其结构进行了表征。生物活性测试结果表明,部分化合物对人体宫颈癌细胞(Hela)、乳腺癌细胞(MDA-MB-231)、前列腺癌细胞(PC-3)和肝癌细胞(Hep G-2)具有良好的抑制活性。在浓度为100μmol/L时,N-[4-(异海松酰胺基)苯基]-2-氯-5-吡啶磺酰胺(Ⅴd)和N-[4-(异海松酰胺基)苯基]-3-溴-2-氯吡啶-5-磺酰胺(Ⅴe)对4种人体肿瘤细胞都具有良好的抑制活性,对上述人体肿瘤细胞的增殖抑制率均大于95%和94%;N-[4-(异海松酰胺基)苯基]-3-氯喹啉磺酰胺(Ⅴc)对上述肿瘤细胞的增殖具有较好的抑制活性。化合物Ⅴd和Ⅴe对4种肿瘤细胞的半抑制浓度(IC50)均低于临床上应用较广的抗癌剂5-氟尿嘧啶(5-FU),其抑制活性优于阳性对照,且对人体正常细胞——人脐静脉内皮细胞(HUVEC)的毒性低于对肿瘤细胞的毒性,有一定的临床应用前景。
In order to find new anti-tumor drugs from natural resources,six novel N-[4-(isopimaramid)phenyl]-heterocychie sulfonamide compounds(Ⅴa~Ⅴf)were designed and synthesized from isopimric acid.These compounds were characterized by FTIR,^(1)HNMR,^(13)CNMR and MS.The results showed that some compounds had good inhibitory activities against cervical cancer cells(Hela),breast cancer cells(MDA-MB-231),prostate cancer cells(PC-3)and hepatocarcinoma cells(Hep G-2).At 100μmol/L,N-[4-(isopimaramid)phenyl]-2-chloropyridine-5-sulfonamide(Ⅴd)and N-[4-(isopimaramid)phenyl]-3-bromo-2-chloropyridine-5-sulfonamide(Ⅴe)exhibited favourable inhibitory activity against the above human tumor cells,and the corresponding inhibition rates of proliferation of the above human tumor cells were all more than 95%and 94%.N-[4-(isopimaramid)phenyl]-3-chloroquinoline-sulfonamide(Ⅴc)had good inhibitory activity on the above four human tumor cells.The median inhibitory concentration(IC50)values of compoundsⅤd andⅤe were lower than that of 5-fluorouracil(5-FU)which was widely used in clinic.The toxicity to human umbilical vein endothelial cells(HUVEC)was lower than that to tumor cells,indicating that compoundsⅤd andⅤe have a certain clinical application prospects.