Authors
Ning Tian, Haoyu Ju, Yu Liu, Jinmei Huang, Zhenggang Luan, Qifeng Hou, Qing Chen, Bin Zhang, Jin Huang, Ming-Hua Zeng
Published in
Angewandte Chemie (International ed. in English). Pages e5756541. Jul 03, 2026. Epub Jul 03, 2026.
Abstract
Novel synthetic methods offer significant potential to accelerate drug development, yet there remains a largely unexplored area for efficiently synthesizing metal-based anticancer agents. Herein, we report a novel solvothermal domino reaction of pyridine-2-methylamine (and its 4-OCH3-substituted derivative), benzaldehyde, and CuCl2∙2H2O, which simultaneously achieves ligand synthesis and coordination assembly in one pot and facilely affords innovative dinuclear dicoordinate copper(I) complexes (Cu1 and Cu2) with the in situ-formed bulky steric-hindering tetraarylethane ligands featuring the bis-imidazo[1,5-a]pyridine scaffold. The unique geometry of Cu1 and Cu2 confers physiological stability and vacant coordination sites for efficiently catalyzing Fenton-like reactions. Further studies reveal that Cu2 effectively elevates intracellular copper ion levels to induce cuproptosis, concurrently disrupting cellular redox homeostasis to trigger ferroptosis. The concurrent cuproptosis-ferroptosis activation finally elicits significantly enhanced immunogenic cell death (ICD), which facilitates the antitumor activity of Cu2. Moreover, in combination with immune checkpoint inhibitor αPD-1, Cu2 exhibits improved immunotherapy effects. This work introduces the first small-molecule copper complex that achieves immunotherapy potentiation through cuproptosis-ferroptosis-ICD induction and provides a new pathway for accessing innovative metal-based antitumor agents through such a rationally designed domino reaction.
PMID:
42397940
Bibliographic data and abstract were imported from PubMed on 04 Jul 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 6
- Comments 0