Indolo[3,2-d][1]benzazepines (paullones), indolo[3,2-d][2]benzazepines, and indolo[2,3-d][2]benzazepines (latonduines) are isomeric scaffolds of current medicinal interest. Herein, we prepared a small library of novel indolo[3,2-d][2]benzazepine-derived ligands HL¹–HL⁴ and copper(II) complexes 1–4. All compounds were characterized by spectroscopic methods (¹H and ¹³C NMR, UV–vis, IR) and electrospray ionization (ESI) mass spectrometry, while complexes 2 and 3, in addition, by X-ray crystallography. Their purity was confirmed by HPLC coupled with high-resolution ESI mass spectrometry and/or elemental analysis. The stability of compounds in aqueous solutions in the presence of DMSO was confirmed by ¹H NMR and UV–vis spectroscopy measurements. The compounds revealed high antiproliferative activity in vitro in the breast cancer cell line MDA-MB-231 and hepatocellular carcinoma cell line LM3 in the low micromolar to nanomolar concentration range. Important structure–activity relationships were deduced from the comparison of anticancer activities of HL¹–HL⁴ and 1–4 with those of structurally similar paullone-derived (HL⁵–HL⁷ and 5–7) and latonduine-derived scaffolds (HL⁸–HL¹¹ and 8–11). The high anticancer activity of the lead drug candidate 4 was linked to reactive oxygen species and endoplasmic reticulum stress induction, which were confirmed by fluorescent microscopy and Western blot analysis.

中文翻译：

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吲哚苯并氮杂衍生配体及其铜 (II) 配合物的构效关系的阐明：关键结构成分的作用和对作用机制的深入了解

Indolo[3,2- d ][1]benzazepines (paullones)、indolo[3,2 - d ][2]benzazepines 和 indolo[2,3- d ][2]benzazepines (latonduines) 是目前药用兴趣。在此，我们制备了一个小型的新型吲哚[3,2 - d ][2]苯并氮杂衍生配体HL ¹ – HL ⁴和铜 (II) 配合物1 – 4库。所有化合物均通过光谱方法（¹ H 和¹³ C NMR、UV-vis、IR）和电喷雾电离 (ESI) 质谱法进行表征，而配合物2和3，此外，通过 X 射线晶体学。它们的纯度通过 HPLC 结合高分辨率 ESI 质谱和/或元素分析来确认。^通过1 H NMR 和 UV-vis 光谱测量证实了化合物在 DMSO 存在下在水溶液中的稳定性。这些化合物在低微摩尔至纳摩尔浓度范围内对乳腺癌细胞系 MDA-MB-231 和肝细胞癌细胞系 LM3 显示出高体外抗增殖活性。从HL ¹ – HL ⁴和1 – 4的抗癌活性与结构相似的 paullone 衍生 ( HL⁵ – HL ⁷和5 – 7 ) 和 latonduine 衍生的支架 ( HL ⁸ – HL ¹¹和8 – 11 )。先导候选药物4的高抗癌活性与活性氧和内质网应激诱导有关，荧光显微镜和蛋白质印迹分析证实了这一点。