Thiosemicarbazone Mixed-Valence Cu(I/II) Complex against Lung Adenocarcinoma Cells through Multiple Pathways Involving Cuproptosis.
J Med Chem
; 67(11): 9091-9103, 2024 Jun 13.
Article
en En
| MEDLINE
| ID: mdl-38778566
ABSTRACT
Induction of cuproptosis and targeting of multiple signaling pathways show promising applications in tumor therapy. In this study, we synthesized two thiosemicarbazone-copper complexes ([CuII(L)Cl] 1 and [CuII2CuI(L)2Cl3] 2, where HL is the (E)-N-methyl-2-(phenyl(pyridin-2-yl)methylene ligand), to assess their antilung cancer activities. Both copper complexes showed better anticancer activity than cisplatin and exhibited hemolysis comparable to that of cisplatin. In vivo experiments showed that complex 2 retarded the A549 cell growth in a mouse xenograft model with low systemic toxicity. Primarily, complex 2 kills lung cancer cells in vitro and in vivo by triggering multiple pathways, including cuproptosis. Complex 2 is the first mixed-valent Cu(I/II) complex to induce cellular events consistent with cuproptosis in cancer cells, which may stimulate the development of mixed-valent copper complexes and provide effective cancer therapy.
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1
Bases de datos:
MEDLINE
Asunto principal:
Tiosemicarbazonas
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Cobre
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Complejos de Coordinación
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Neoplasias Pulmonares
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Antineoplásicos
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2024
Tipo del documento:
Article