Citation: 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]. Chinese Journal of Organic Chemistry, ;2019, 39(7): 1962-1969. doi: 10.6023/cjoc201811004 shu

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

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

Corresponding author: Pan Chengxue, chengxuepan@163.com Su Guifa, gfysglgx@163.com

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Received Date: 4 November 2018
Revised Date: 18 January 2019
Available Online: 2 July 2019
Fund Project: the National Natural Science Foundation of China 21462008the Natural Science Foundation of Guangxi Province 2017GXNSFDA198045the Ministry of Education of China IRT_16R15Project 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)the Natural Science Foundation of Guangxi Province 2015GXNSFDA139009

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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.
- benzophenanthridine,
- cyclization reaction,
- analogue of natural product,
- cytotoxicity
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