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

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.