Tricyclic alkaloid-like compounds were synthesised in a few steps, via the bridging Ritter reaction. The compounds were evaluated for their antiproliferative activity against the MCF-7 and the aggressive MDA-MB-231 breast cancer cells. The anti-cancer activities of 2c were found to be selective towards the aggressive and more challenging to treat triple negative (MDA-MB-231) cell line while exhibiting no antiproliferative activities towards the MCF-7 cells at the highest concentration tested (50 μM). The IC₅₀ of compound 2c was determined to be 7.9 μM for the MDA-MB-231 cell line. Furthermore, 2c arrested cell cycle at the G₂/M phase and induced apoptosis in a dose-dependent manner. Besides in-house anti-cancer screening, compound 3 was selected for anti-cancer screening by the National Cancer Institute and was found to have broad anti-cancer activity with selectivity against particular leukaemia, colon, melanoma, and breast cancer cell lines. Cytotoxicities of compounds 2c and 3 were also tested against noncancerous mammalian cells (VERO cell line), and found to be selective towards cancerous cells. The facile synthetic route, unique chemical structures and the biological data make these alkaloid-like compounds worthwhile lead compounds for further anti-cancer drug development.

中文翻译：

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类生物碱化合物的抗增殖活性

三桥生物碱样化合物是通过桥接Ritter反应在几个步骤中合成的。评价化合物对MCF-7和侵袭性MDA-MB-231乳腺癌细胞的抗增殖活性。发现2c的抗癌活性对侵袭性具有选择性，对治疗三阴性（MDA-MB-231）细胞系更具挑战性，而在测试的最高浓度（50μM）下对MCF-7细胞则无抗增殖活性）。对于MDA-MB-231细胞系，化合物2c的IC ₅₀确定为7.9μM。此外，2c在G ₂处阻滞了细胞周期/ M期和诱导细胞凋亡的剂量依赖性。除了进行内部抗癌筛选外，化合物3还被美国国家癌症研究所（National Cancer Institute）筛选用于抗癌筛选，并发现它具有广泛的抗癌活性，并且对特定的白血病，结肠癌，黑素瘤和乳腺癌细胞系具有选择性。还测试了化合物2c和3对非癌性哺乳动物细胞（VERO细胞系）的细胞毒性，发现对癌细胞具有选择性。简便的合成路线，独特的化学结构和生物学数据使这些生物碱样化合物值得进一步开发抗癌药物中的先导化合物。