A series of novel β-carbolines with a flexible amino side chain at positions 1 and 3, respectively, were designed, synthesized and evaluated as potential antitumor agents. The results revealed that most of the compounds exhibited a broad spectrum of antiproliferative activity with IC50 value lower than 20 μM against human tumor cell lines. Among them, compound 2f was the most potent antiproliferative agent with IC50 value below 5.0 μM against human tumor cell lines. Subsequent studies on the in vivo antitumor efficacy of the representative compound 2f demonstrated its ability to hinder tumor progression and significantly diminish tumor mass in a mouse model of colorectal cancer. Further investigation on mechanisms of action showed that compound 2f induced autophagy via the ATG5/ATG7 pathway in HCT116 cells. These compounds may contribute to the development of therapeutic agents for colorectal cancer.

中文翻译：

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通过靶向自噬在结直肠癌中设计、合成和生物学评价新型 β-咔啉作为抗肿瘤药物


设计、合成了一系列在第 1 位和第 3 位分别具有柔性氨基侧链的新型 β-咔啉，并作为潜在的抗肿瘤药物进行了评价。结果表明，大多数化合物表现出广谱的抗增殖活性，对人肿瘤细胞系的 IC50 值低于 20 μM。其中，化合物 2f 是最有效的抗增殖剂，对人肿瘤细胞系的 IC50 值低于 5.0 μM。随后对代表性化合物 2f 的体内抗肿瘤功效的研究表明，它能够在结直肠癌小鼠模型中阻止肿瘤进展并显着减少肿瘤质量。对作用机制的进一步研究表明，化合物 2f 通过 ATG5/ATG7 通路诱导 HCT116 细胞自噬。这些化合物可能有助于结直肠癌治疗剂的开发。