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2019 , Vol. 39 >Issue 12: 3532 - 3541

DOI: https://doi.org/10.6023/cjoc201905029

研究论文

新型异甜菊醇衍生物的合成、表征及生物活性研究

  • 郭永泰 ,
  • 侯熙彦 ,
  • 郑昌吉 ,
  • 赵春晖 ,
  • 金宇婷 ,
  • 高雪琴 ,
  • 王倩 ,
  • 孙蕾 ,
  • 赵龙铉 ,
  • 朴花
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  • a 辽宁师范大学化学化工学院 辽宁大连 116029;
    b 大连民族大学生命科学学院 辽宁大连 116600;
    c 延边大学药学院 吉林延吉 133002;
    e 辽宁师范大学 生物技术与分子药物研发辽宁省重点实验室 辽宁大连 116029;
    e 大连医科大学基础医学院 辽宁大连 116044

收稿日期: 2019-05-13

  修回日期: 2019-06-26

  网络出版日期: 2019-08-01

基金资助

国家自然科学基金（No.21101067）资助项目.

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Synthesis, Characteristics and Bioactivities of Novel Isosteviol Derivatives

  • Guo Yongtai ,
  • Hou Xiyan ,
  • Zheng Changji ,
  • Zhao Chunhui ,
  • Jin Yuting ,
  • Gao Xueqin ,
  • Wang Qian ,
  • Sun Lei ,
  • Zhao Longxuan ,
  • Piao Hua
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  • a School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian, Liaoning 116029;
    b College of Life Science, Dalian Nationalities University, Dalian, Liaoning 116600;
    c College of Pharmacy, Yanbian University, Yanji, Jilin 133002;
    d Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, Liaoning Normal University, Dalian, Liaoning 116029;
    e Department of Physiology, College of Basic Medical Sciences, Dalian Medical University, Dalian, Liaoning 116044

Received date: 2019-05-13

  Revised date: 2019-06-26

  Online published: 2019-08-01

Supported by

Project supported by the National Natural Science Foundation of China (No. 21101067).

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摘要

以异甜菊醇为先导化合物，通过连接片段分别在C-16和C-19位引入吗啉和哌嗪结构，并对D环进行结构改造，设计合成了15种未见文献报道的异甜菊醇衍生物，并观察其对人皮肤鳞癌细胞（Colo-16）和人肺腺癌细胞（A549）抑制作用.生物活性结果显示，有4种化合物对人皮肤鳞状癌细胞（Colo-16）的抑制活性明显优于阳性对照物5-氟尿嘧啶.同时观察其对大肠杆菌（E.coli 1924）、金黄色葡萄球菌（S.aureus 4220）、变形链球菌（S.mutans 3289）、耐甲氧西林金黄色葡萄球菌（MRSA 3167）和耐喹诺酮金黄色葡萄球菌（QRSA 3505）的抑制作用，结果显示，有6种化合物对S.mutans 3289的最小抑菌浓度（MIC）为8 μg/mL，与阳性对照物氯霉素相当；16β-O-[5-氧亚基-5-（4-甲基-1-哌嗪基）-戊酰基]-19-贝叶酸乙酯（IS-12b）对MRSA 3167的最小抑菌浓度（MIC）为8 μg/mL，与阳性对照物氯霉素相当.

关键词： 异甜菊醇; 细胞毒活性; 抑菌活性

本文引用格式

郭永泰 , 侯熙彦 , 郑昌吉 , 赵春晖 , 金宇婷 , 高雪琴 , 王倩 , 孙蕾 , 赵龙铉 , 朴花 . 新型异甜菊醇衍生物的合成、表征及生物活性研究[J]. 有机化学, 2019 , 39(12) : 3532 -3541 . DOI: 10.6023/cjoc201905029

Abstract

Fifteen novel isosteviol derivatives were designed and synthesized by introducing morpholine and piperazine moieties into C-16 and C-19 position through connecting fragments, and the D-ring structure was modified. The inhibitory effects on Colo-16 and A549 were observed, the results showed that the inhibitory activities of 4 compounds on Colo-16 were significantly better than the positive control of 5-fluorouracil. The inhibitory effects on E. coli 1924, S. aureus 4220, S. mutans 3289, MRSA 3167 and QRSA 3505 were also observed, the results showed that the minimum inhibitory concentration (MIC) of 6 compounds on S. mutans 3289 was 8 μg/mL, which was comparable to the positive control chloramphenicol. The MIC of 16β-O-(5-oxo-5-(4-methyl-1-piperazinyl)-valeryl)]-19-beyeran acid ethyl ester (IS-12b) on MRSA 3167 was 8 μg/mL, which was comparable to the positive control chloramphenicol.

Key words： isosteviol; cytotoxic activity; antibacterial activity

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