愈创木薁衍生物的设计合成及其抗氧化、抗炎活性研究  

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

作　　者：李蕾 朱聪聪 朱全刚 陈中建 高希珂[2] Lei Li;Congcong Zhu;Quangang Zhu;Zhongjian Chen;Xike Gao(College of Chemistry and Materials Science,Shanghai Normal University,Shanghai 200234;Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional Molecules,Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences,Shanghai 200032;Shanghai Skin Disease Hospital,Shanghai 200443;Shanghai Engineering Research Center for Topical Chinese Medicine,Shanghai 200443)

机构地区：[1]上海师范大学化学与材料科学学院,上海200234 [2]中国科学院上海有机化学研究所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 [3]上海市皮肤病医院,上海200443 [4]上海中药外用制剂创新工程技术研究中心,上海200443

出　　处：《有机化学》2022年第9期2906-2913,共8页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.22075310);上海市科学技术委员会(Nos.19XD1424700,20DZ2255200)资助项目。

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(IC_(50)值为5.64μg/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.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 IC_(50) 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.

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 

分 类 号：TQ460.1[化学工程—制药化工]