Study on the Synthesis of Benzophenanthridine Analogues via the Cyclization Reaction of Aryl-enamine Ester and Their Cytotoxicity

doi:10.6023/cjoc201811004

Chin. J. Org. Chem. ›› 2019, Vol. 39 ›› Issue (7): 1962-1969.DOI: 10.6023/cjoc201811004 Previous Articles Next Articles

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基于芳基烯胺酯的环化反应合成苯并菲啶类似物及其细胞毒活性研究

王增博, 田成, 刘晴晴, 张玮, 潘成学, 苏桂发

广西师范大学化学与药学学院药用资源化学与药物分子工程国家重点实验室桂林 541004

收稿日期:2018-11-04 修回日期:2019-01-18 发布日期:2019-04-08
通讯作者: 潘成学, 苏桂发 E-mail:chengxuepan@163.com;gfysglgx@163.com
基金资助:
国家自然科学基金（No.21462008）、广西自然科学基金（Nos.2015GXNSFDA139009，2017GXNSFDA198045）和教育部创新团队基金（No.IRT_16R15）资助项目.

Study on the Synthesis of Benzophenanthridine Analogues via the Cyclization Reaction of Aryl-enamine Ester and Their Cytotoxicity

Wang Zengbo, Tian Cheng, Liu Qingqing, Zhang Wei, Pan Chengxue, Su Guifa

State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources;School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004

Received:2018-11-04 Revised:2019-01-18 Published:2019-04-08
Contact: 10.6023/cjoc201811004 E-mail:chengxuepan@163.com;gfysglgx@163.com
Supported by:
Project supported by the National Natural Science Foundation of China (No. 21462008), the Natural Science Foundation of Guangxi Province (Nos. 2015GXNSFDA139009, 2017GXNSFDA198045), and the Ministry of Education of China (No. IRT_16R15).

1. Study on the Synthesis of Benzophenanthridine Analogues via the Cyclization Reaction of Aryl-enamine Ester and Their Cytotoxicity.PDF(3272KB)

Abstract

Study on the synthesis and bioactivity of benzophenanthridine alkaloids or its analogues had been the interests of many reserach groups who dedicated to organic synthsis or medicinal chemistry, due to their broad spectrum of biological activities such as antitumor, antiviral, antiinflammatory, antibacterial and so on. In this paper, twenty three novel analogue of benzophenanthridines were synthesized starting from isochroman-3-one and aromatic amines in 3~4 steps via the cyclization reaction of aryl-enamine ester as the key transformation. The structures of the targeted compounds were characterized and comfirmed by ¹H NMR, ¹³C NMR and HRMS. In vitro cytotoxic activity against a panel of human tumor cell lines (MGC-803, HepG2, NCI-H460, SKOV3, T-24) and nomal cell HL-7702 was also evaluated via methyl thiazolyl tetrazolium (MTT) assay. The result indicated that only a very few of the targeted compounds exhibted moderate cytotoxic activity against the tested cell lines. Among them 2,3-dimethoxy-isochrysen[4,3-c]quinoline (4j) and 2-chloro-isochromone[4,3-c]quinoline (5f) displayed moderate antiproliferative activity against human tumor cell lines on T-24 and NCI-H460 with IC₅₀ values of 15.8 and 16.7 μmol/L, respectively.

Key words: benzophenanthridine, cyclization reaction, analogue of natural product, cytotoxicity

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Wang Zengbo, Tian Cheng, Liu Qingqing, Zhang Wei, Pan Chengxue, Su Guifa. Study on the Synthesis of Benzophenanthridine Analogues via the Cyclization Reaction of Aryl-enamine Ester and Their Cytotoxicity[J]. Chin. J. Org. Chem., 2019, 39(7): 1962-1969.

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基于芳基烯胺酯的环化反应合成苯并菲啶类似物及其细胞毒活性研究

Study on the Synthesis of Benzophenanthridine Analogues via the Cyclization Reaction of Aryl-enamine Ester and Their Cytotoxicity

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