天然黄酮Mannich碱衍生物的合成及生物活性研究

doi:10.3969/j.issn.0253-2417.2016.01.005

林产化学与工业 ›› 2016, Vol. 36 ›› Issue (1): 35-41.doi: 10.3969/j.issn.0253-2417.2016.01.005

天然黄酮Mannich碱衍生物的合成及生物活性研究

刘重阳¹, 阮文山^1,2, 王盛淳¹, 汪秋安¹

1. 湖南大学化学化工学院, 湖南长沙 410082;
2. 胡志明市工业大学化工系, 越南胡志明 999100

收稿日期:2015-03-30 出版日期:2016-02-25 发布日期:2016-03-18
通讯作者: 汪秋安(1962-),男,教授,博士生导师,主要从事天然产物化学和有机合成研究;E-mail:WangQA@hnu.edu.cn。 E-mail:WangQA@hnu.edu.cn
作者简介:刘重阳(1988-),男,湖北黄冈人,硕士生,从事天然产物化学合成与改性研究
基金资助:
"十二五"国家科技支撑计划资助(2012BAD31B02);国家自然科学基金资助项目(J1210040)

Synthesis and Bioactivity of Natural Flavones Mannich Base Derivatives

LIU Chong-yang¹, NGUYEN Vanson^1,2, WANG Sheng-chun¹, WANG Qiu-an¹

1. College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China;
2. Faculty of Chemical Engineering, Industry University of Hochiminh City, Hochiminh 999100, Vietnam

Received:2015-03-30 Online:2016-02-25 Published:2016-03-18

摘要/Abstract

摘要： 以柚皮苷和橙皮苷为原料,经碘/吡啶脱氢,O-甲基化和糖苷水解等反应,分别合成了2种天然黄酮芹菜素-5,4'-二甲醚(1)和木犀草素-5,3',4'-三甲醚(2)。然后以1和2为底物,分别与甲醛、二级胺在酸性醇溶剂中发生微波协助的Mannich反应,对黄酮8-位进行胺甲基化修饰,合成了15个新型黄酮Mannich碱衍生物3~17。所合成的化合物经¹H NMR、¹³C NMR和MS等进行了结构确证, 并采用细胞计数Kit-8(CCK-8)法测试了化合物1~17对子宫颈癌Hela细胞的体外抑制活性。结果表明,化合物1、2、7、9、10、12和17对Hela细胞增殖具有明显的抑制活性,其中化合物10、12和17的半数抑制浓度(IC₅₀)分别为16.13、29.04和9.14 μmol/L,活性高于阳性对照药物顺铂(IC₅₀为41.25 μmol/L)。

关键词: 黄酮类, Mannich碱衍生物, 合成, 生物活性

Abstract: Two naturally occurring flavones, apigenin-5, 4'-dimethy ether(1) and lutedin-5, 3', 4'-trimethyl ether(2), were synthesized through I₂/Py dehydrogenation, O-methylation and glycoside hydrolysis reaction, using naringin and hesperidin as raw materials.Based on Mannich reaction of flavones 1 or 2 with various secondary amines and formaldehyde in acidic alcohol solvent with microwave assisted, fifteen novel flavones Mannich base derivatives 1-17 were synthesized.The structures of all synthesized compounds were confirmed by ¹H NMR, ¹³C NMR and MS techniques.Furthermore, all compounds were tested for anti-proliferative activities on human cervical carcinoma Hela cells using cell counting Kit-8(CCK-8).The results showed that compounds 1, 2, 7, 9, 10, 12 and 17 exhibited distinct anti-proliferative activities against Hela cells.Among them, compounds 10, 12 and 17 displayed higher activities with inhibitory concentration 50%(IC₅₀) of 16.13, 29.04 and 9.14 μmol/L than the positive control cis-platin(IC₅₀=41.25 μmol/L).

Key words: flavones, Mannich base derivatives, synthesis, bioactivity

中图分类号:

TQ35

刘重阳, 阮文山, 王盛淳, 汪秋安. 天然黄酮Mannich碱衍生物的合成及生物活性研究[J]. 林产化学与工业, 2016, 36(1): 35-41.

LIU Chong-yang, NGUYEN Vanson, WANG Sheng-chun, WANG Qiu-an. Synthesis and Bioactivity of Natural Flavones Mannich Base Derivatives[J]. Chemistry and Industry of Forest Products, 2016, 36(1): 35-41.

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天然黄酮Mannich碱衍生物的合成及生物活性研究

Synthesis and Bioactivity of Natural Flavones Mannich Base Derivatives

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