(1E,4E)-1,5双(2,3-二甲氧基苯基)戊-1,4-二烯-3-酮类似物的合成及其体外抗胃癌活性的研究

成佳美, 王佩华, 朱敏, 赵敏, 吴建章, 汪佳兵

中国药学杂志 ›› 2018, Vol. 53 ›› Issue (23) : 1978-1983.

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中国药学杂志
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中国药学杂志 ›› 2018, Vol. 53 ›› Issue (23) : 1978-1983. DOI: 10.11669/cpj.2018.23.002
论著

(1E,4E)-1,5双(2,3-二甲氧基苯基)戊-1,4-二烯-3-酮类似物的合成及其体外抗胃癌活性的研究

  • 成佳美1, 王佩华1, 朱敏1, 赵敏1, 吴建章1*, 汪佳兵1,2*
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Synthesis of (1E,4E)-1,5-bis(2,3-dimethoxyphenyl)penta-1,4-dien-3-one Analogs and Its Anti-gastric Cancer Activity In Vitro

  • CHENG Jia-mei1, WANG Pei-hua1, ZHU-Min1, ZHAO-Min1, WU Jian-zhang1*, WANG Jia-bing1,2*
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摘要

目的 寻找不对称单羰基姜黄素类似物高效经济的合成方法,并设计合成一系列B19类似物及初步探讨其体外抗胃癌活性。方法 通过药物化学拼合原理,设计出一系列含2,3-二甲氧基苯基的不对称B19类似物,并得到用L-脯氨酸催化一步合成中间体(E)-2-(2,3-二甲氧基亚苄基)环戊酮的方法。目标产物经四甲基偶氮唑蓝(MTT)法筛选,并用集落克隆实验进一步验证其体外抗胃癌活性。结果 合成得到10个结构全新的目标化合物,用LC-MS和1H-NMR表征其结构。其中6e对胃癌细胞SGC-7901和BGC-823的生长活性抑制最高,IC50分别为9.80和13.50 μmol·L-1。结论 L-脯氨酸可作为高效经济合成不对称单羰基姜黄素类似物的催化剂。活性化合物6e具有较好的体外抗胃癌活性,其毒性及对肿瘤细胞生长抑制机制有待进一步研究。

Abstract

OBJECTIVE To explore the efficient and economical synthesis method of asymmetric monocarbonyl curcumin analogues(AMCACs), design and sgnthesize a series of B19(1E,4E)-1,5-bis(2,3-dimethoxyphenyl)penta-1,4-dien-3-one analogs to investigate their anti-gastric cancer activities in vitro.METHODS A series of asymmetric B19 analogues containing 2,3-dimethoxyphenyl were designed via the combination principle of medicinal chemistry, and obtained a method for synthesizing intermediate (E)-2-(2,3- dimethoxybenzylidene)cyclopentanone by one step catalyzed by L-proline. The targeted compounds were screened by MTT assay, and colony cloning experiments were used to further verify its anti-gastric cancer activity in vitro.RESULTS Ten novel target compounds were synthesized, and the structures were confirmed by LC-MS and 1H-NMR spectral analysis. Among them, compound 6e had the highest inhibitory activity on the growth of gastric cancer cells SGC-7901 and BGC-823, whose IC50 were 9.80 and 13.50 μmol·L-1, respectively.CONCLUSION L-proline could be used as a catalyst to synthesize asymmetric monocarbonyl curcumin analogues efficiently and economically. Compound 6e could effectively inhibit the growth of gastric cancer cells in vitro, and its toxicity and inhibition mechanism of tumor cell growth need to be further studied.

关键词

不对称单羰基姜黄素类似物 / (1E,4E)-1,5双(2,3-二甲氧基苯基)戊-1,4-二烯-3-酮 / 抗胃癌活性

Key words

asymmetric monocarbonyl curcumin analogues / (1E,4E)-1,5-bis(2,3-dimethoxyphenyl)penta-1,4-dien-3-one / anti-gastric cancer activity

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成佳美, 王佩华, 朱敏, 赵敏, 吴建章, 汪佳兵. (1E,4E)-1,5双(2,3-二甲氧基苯基)戊-1,4-二烯-3-酮类似物的合成及其体外抗胃癌活性的研究[J]. 中国药学杂志, 2018, 53(23): 1978-1983 https://doi.org/10.11669/cpj.2018.23.002
CHENG Jia-mei, WANG Pei-hua, ZHU-Min, ZHAO-Min, WU Jian-zhang, WANG Jia-bing. Synthesis of (1E,4E)-1,5-bis(2,3-dimethoxyphenyl)penta-1,4-dien-3-one Analogs and Its Anti-gastric Cancer Activity In Vitro[J]. Chinese Pharmaceutical Journal, 2018, 53(23): 1978-1983 https://doi.org/10.11669/cpj.2018.23.002
中图分类号： R965   

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基金

浙江省自然科学基金项目资助(LY17H160059);大学生创新创业训练项目资助(20170343004);温州医科大学本专科学生科研立项资助(wxy2017101038);浙江省大学生科技创新活动计划资助(2018R413038)

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