摘要/Abstract

苯并菲啶生物碱具有抗肿瘤、抗病毒、抗炎及抗菌等广泛生物活性，因此其类似物的合成与活性研究引起了许多有机合成及药物化学研究者的兴趣.以3-异色酮及芳胺等为原料，以烯胺酯的环化反应为关键步骤，经3～4步反应合成了23个未见文献报道的苯并菲啶类似物，目标化合物结构经¹H NMR，¹³C NMR和HRMS表征和确认.采用噻唑蓝（MTT）法测试了目标化合物对人肿瘤细胞MGC-803，HepG2，NCI-H460，SKOV3，T-24和人正常细胞HL-7702的体外细胞毒活性.发现只有很少量化合物对受试肿瘤细胞显示中等强度的增殖抑制活性，其中2，3-二甲氧基-6（1H）-异色并[4，3-c]喹啉（4j）对人膀胱癌细胞T-24和2-氯异色酮并[4，3-c]喹啉（5f）对人肺癌细胞NCI-H460的IC₅₀值分别为15.8和16.7 μmol/L.
关键词: 苯并菲啶生物碱, 环化反应, 天然产物类似物, 细胞毒活性
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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