Aili Li , Weiping Pan , ZhenLei Zhang , Feng Yang , Yi Gou , Ye Zhang , Libing Ma
{"title":"腙铜（II）配合物通过激活多种抗癌途径抑制肺腺癌","authors":"Aili Li , Weiping Pan , ZhenLei Zhang , Feng Yang , Yi Gou , Ye Zhang , Libing Ma","doi":"10.1016/j.bioorg.2024.107994","DOIUrl":null,"url":null,"abstract":"<div><div>Activating multiple anti-cancer pathways has great potential for tumor treatment. Herein, we synthesized two binuclear Cu(II) hydrazone complexes ([Cu<sub>2</sub>(HL1)<sub>2</sub>Cl<sub>2</sub>] 1 and [Cu<sub>2</sub>(HL1)<sub>2</sub>Br<sub>2</sub>] 2) and two mononuclear hydrazone-Cu(II) complexes ([Cu(HL2)Cl]·CH<sub>3</sub>OH 3 and [Cu(HL2)(H<sub>2</sub>O)Br]·2H<sub>2</sub>O 4), to evaluate their anti-lung cancer activities. MTT assays revealed that the Cu(II) complexes demonstrate superior anticancer activity compared to <em>cis</em>platin. Among them, complex 3 exhibited selective toxicity towards A549 cancer cells in comparison to normal cells and demonstrated hemolytic activity comparable to <em>cis</em>platin. 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 <em>in vivo</em> and <em>in vitro</em> 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.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"154 ","pages":"Article 107994"},"PeriodicalIF":4.5000,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Hydrazone copper(II) complexes suppressed lung adenocarcinoma by activating multiple anticancer pathway\",\"authors\":\"Aili Li , Weiping Pan , ZhenLei Zhang , Feng Yang , Yi Gou , Ye Zhang , Libing Ma\",\"doi\":\"10.1016/j.bioorg.2024.107994\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Activating multiple anti-cancer pathways has great potential for tumor treatment. Herein, we synthesized two binuclear Cu(II) hydrazone complexes ([Cu<sub>2</sub>(HL1)<sub>2</sub>Cl<sub>2</sub>] 1 and [Cu<sub>2</sub>(HL1)<sub>2</sub>Br<sub>2</sub>] 2) and two mononuclear hydrazone-Cu(II) complexes ([Cu(HL2)Cl]·CH<sub>3</sub>OH 3 and [Cu(HL2)(H<sub>2</sub>O)Br]·2H<sub>2</sub>O 4), to evaluate their anti-lung cancer activities. MTT assays revealed that the Cu(II) complexes demonstrate superior anticancer activity compared to <em>cis</em>platin. Among them, complex 3 exhibited selective toxicity towards A549 cancer cells in comparison to normal cells and demonstrated hemolytic activity comparable to <em>cis</em>platin. 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 <em>in vivo</em> and <em>in vitro</em> 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.</div></div>\",\"PeriodicalId\":257,\"journal\":{\"name\":\"Bioorganic Chemistry\",\"volume\":\"154 \",\"pages\":\"Article 107994\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-11-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Bioorganic Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S004520682400899X\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S004520682400899X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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.
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.
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