Lysosomes have become a hot topic in tumor therapy; targeting the lysosome is therefore a promising strategy in cancer therapy. Based on our previous lysosome-targeted bio-imaging agent, homospermine-benzo[cd]indol-2(1H)-one conjugate (HBC), we further developed three novel series of polyamine- benzo[cd]indol-2(1H)-one conjugates. Among them, compound 15f showed potent inhibitory activity in hepatocellular carcinoma migration both in vitro and in vivo. Our study results showed that compound 15f entered the cancer cells via the polyamine transporter localized in the lysosomes and caused autophagy and apoptosis. The mechanism of action revealed that the crosstalk between autophagy and apoptosis induced by 15f was mutually reinforcing patterns. Besides, 15f also targeted lysosomes and exhibited stronger green fluorescence than HBC, which indicated its potential as an imaging agent. To summarize, compound 15f could be used as a valuable dual-functional lead compound for future development against liver-cancer metastasis and lysosome imaging.

中文翻译：

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Benzo[cd]indol-2(1H)-ones 衍生物作为溶酶体靶向抗转移剂的设计、合成和生物学评价。

溶酶体已成为肿瘤治疗的热门话题；因此，靶向溶酶体是癌症治疗中一种很有前景的策略。基于我们之前的溶酶体靶向生物成像剂 homospermine-benzo[cd]indol-2(1H)-one 共轭物 (HBC)，我们进一步开发了三个新系列的多胺-苯并 [cd]indol-2(1H) -一共轭。其中，化合物15f在体外和体内均显示出有效的肝细胞癌迁移抑制活性。我们的研究结果表明，化合物15f通过位于溶酶体中的多胺转运蛋白进入癌细胞并引起自噬和细胞凋亡。作用机制表明，15f 诱导的自噬和细胞凋亡之间的串扰是相辅相成的模式。此外，15f 还靶向溶酶体并表现出比 HBC 更强的绿色荧光，这表明其作为显像剂的潜力。总而言之，化合物 15f 可用作有价值的双功能先导化合物，用于未来针对肝癌转移和溶酶体成像的开发。