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2022 , Vol. 42 >Issue 9: 2906 - 2913

DOI: https://doi.org/10.6023/cjoc202204025

研究论文

愈创木薁衍生物的设计合成及其抗氧化、抗炎活性研究

  • 李蕾 ,
  • 朱聪聪 ,
  • 朱全刚 ,
  • 陈中建 ,
  • 高希珂
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  • a 上海师范大学化学与材料科学学院 上海 200234
    b 中国科学院上海有机化学研究所 中国科学院有机功能分子合成与组装化学重点实验室 上海 200032
    c 上海市皮肤病医院 上海 200443
    d 上海中药外用制剂创新工程技术研究中心 上海 200443

收稿日期: 2022-04-11

  修回日期: 2022-05-19

  网络出版日期: 2022-06-09

基金资助

国家自然科学基金(22075310); 上海市科学技术委员会(19XD1424700); 上海市科学技术委员会(20DZ2255200)

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Design, Synthesis and Bioactivity Evaluation of Guaiazulene Derivatives with Antioxidant and Anti-inflammatory Activities

  • Lei Li ,
  • Congcong Zhu ,
  • Quangang Zhu ,
  • Zhongjian Chen ,
  • Xike Gao
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  • a College of Chemistry and Materials Science, Shanghai Normal University, Shanghai 200234
    b Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional Molecules, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032
    c Shanghai Skin Disease Hospital, Shanghai 200443
    d Shanghai Engineering Research Center for Topical Chinese Medicine, Shanghai 200443
* Corresponding authors. E-mail: ;
;

Received date: 2022-04-11

  Revised date: 2022-05-19

  Online published: 2022-06-09

Supported by

National Natural Science Foundation of China(22075310); Science and Technology Commission of Shanghai Municipality(19XD1424700); Science and Technology Commission of Shanghai Municipality(20DZ2255200)

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摘要

动植物来源的愈创木薁(GA)具有抗菌、抗氧化、抗炎、抗过敏和低毒等特点, 其水溶性衍生物愈创木薁磺酸钠(GAS-Na)同样具有抗炎、促进上皮细胞生长和促进伤口愈合的作用. 然而, 商品化活性分子GA和GAS-Na对光、热等稳定性较差. 为了探索具有更高活性和稳定性的愈创木薁类生物功能分子, 合成了2,2'-二愈创木薁(BGA)和[2,2'-二愈创木薁]-1,1'-二磺酸钠(BGAS-Na), 并以GA和GAS-Na为对照, 评价了四个化合物的抗氧化能力, 研究了其对脂多糖(LPS)诱导小鼠巨噬细胞RAW 264.7的NO释放及细胞存活率的影响. 结果表明, BGA和BGAS-Na具有良好的抗氧化能力, 且稳定性较GA和GAS-Na有所提升; BGAS-Na在抗炎活性测试中具有最优的NO抑制率(IC50值为5.64 μg/mL), 优于商品化分子GAS-Na, 且该抑制作用具有浓度依赖性. 此外, 四种化合物均不影响巨噬细胞的生长, 具有较低的细胞毒性. 因此, BGAS-Na有望成为具有发展潜力的抗炎药物.

关键词： 愈创木薁; 愈创木薁磺酸钠; 抗氧化; 抗炎; 细胞毒性; 巨噬细胞

本文引用格式

李蕾 , 朱聪聪 , 朱全刚 , 陈中建 , 高希珂 . 愈创木薁衍生物的设计合成及其抗氧化、抗炎活性研究[J]. 有机化学, 2022 , 42(9) : 2906 -2913 . DOI: 10.6023/cjoc202204025

Abstract

Animal and plant-derived guaiazulene (GA) has the characteristics of antimicrobial, antioxidant, anti-inflammatory, anti-allergic and low toxicity. Sodium guaiazulene sulfonate (GAS-Na), a water-soluble derivative of GA, also has the effects of anti-inflammatory, promoting epithelial cell growth and wound healing. However, the commercial active molecules GA and GAS-Na have poor stability to light and heat. Therefore, in order to explore the guaiazulene biomedical functional molecules with higher activity and stability, 2,2'-biguaiazulene (BGA) and (2,2'-biguaiazulene)-1,1'-disulfonic acid sodium (BGAS-Na) were synthesized. Compared with GA and GAS-Na, the antioxidant activities of BGA and BGAS-Na were evaluated, and their biological effects on NO release and cell viability of LPS-induced RAW 264.7 macrophages were studied. The results showed that BGA and BGAS-Na had better antioxidant capacity and improved stability compared with GA and GAS-Na; BGAS-Na had the best NO inhibition rate in the anti-inflammatory activity test (the IC50 value was 5.64 μg/ mL), which was better than that of the commercial molecule GAS-Na, and the inhibitory effect was dose-dependent. In addition, the four compounds did not affect the growth of macrophages and had low cytotoxicity. Therefore, BGAS-Na is expected to become a potential anti-inflammatory drug.

Key words： guaiazulene; sodium guaiazulene sulfonate; antioxidant; anti-inflammatory; cytotoxicity; macrophages

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