Hydrazone copper(II) complexes suppressed lung adenocarcinoma by activating multiple anticancer pathway

IF 4.5 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioorganic Chemistry Pub Date : 2024-11-26 DOI:10.1016/j.bioorg.2024.107994

Aili Li , Weiping Pan , ZhenLei Zhang , Feng Yang , Yi Gou , Ye Zhang , Libing Ma

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Abstract

Activating multiple anti-cancer pathways has great potential for tumor treatment. Herein, we synthesized two binuclear Cu(II) hydrazone complexes ([Cu₂(HL1)₂Cl₂] 1 and [Cu₂(HL1)₂Br₂] 2) and two mononuclear hydrazone-Cu(II) complexes ([Cu(HL2)Cl]·CH₃OH 3 and [Cu(HL2)(H₂O)Br]·2H₂O 4), to evaluate their anti-lung cancer activities. MTT assays revealed that the Cu(II) complexes demonstrate superior anticancer activity compared to cisplatin. Among them, complex 3 exhibited selective toxicity towards A549 cancer cells in comparison to normal cells and demonstrated hemolytic activity comparable to cisplatin. The low toxicity and effective antitumor capabilities of complex 3 have been confirmed in xenograft experiments using A549 tumor-bearing mice. Interestingly, complex 3 eradicates lung tumor cells both in vivo and in vitro by initiating multiple anticancer pathways, including cuproptosis. Our research extends the study of hydrazone copper complexes and provides strategies for the treatment of lung cancer.

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腙铜（II）配合物通过激活多种抗癌途径抑制肺腺癌

激活多种抗癌途径在肿瘤治疗中具有巨大潜力。在此，我们合成了两种双核铜(II)腙配合物（[Cu2(HL1)2Cl2] 1 和 [Cu2(HL1)2Br2] 2）和两种单核腙-铜(II)配合物（[Cu(HL2)Cl]-CH3OH 3 和 [Cu(HL2)(H2O)Br]-2H2O 4），以评估它们的抗肺癌活性。MTT 分析表明，与顺铂相比，Cu(II) 复合物具有更强的抗癌活性。其中，与正常细胞相比，复合物 3 对 A549 癌细胞具有选择性毒性，其溶血活性与顺铂相当。利用 A549 肿瘤小鼠进行的异种移植实验证实了复合物 3 的低毒性和有效抗肿瘤能力。有趣的是，复合物 3 通过启动多种抗癌途径（包括杯突酶），在体内和体外都能消灭肺肿瘤细胞。我们的研究拓展了对腙铜复合物的研究，并为肺癌的治疗提供了策略。

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来源期刊

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.