New copper() complexes selective for prostate cancer cells

A new family of eighteen Cu( i ) complexes of the general formula [Cu(PP)(LL)][BF 4 ], where PP is a phosphane ligand and LL represents an N,O-heteroaromatic bidentate ligand, has been synthesized and fully characterized by classical analytical and spectroscopic methods. Five complexes of this serie...

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Published in:Dalton transactions : an international journal of inorganic chemistry 2020-09, Vol.49 (35), p.12273-12286
Main Authors: Machado, João Franco, Sequeira, Diogo, Marques, Fernanda, Piedade, M. Fátima M, Villa de Brito, Maria J, Helena Garcia, M, Fernandes, Alexandra R, Morais, Tânia S
Format: Article
Language:English
Subjects:
Apoptosis
Cell death
Coordination compounds
Copper
Copper compounds
Crystallography
Cytotoxicity
Ethane
Ligands
Necrosis
Prostate cancer
Single crystals
Toxicity
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Summary:A new family of eighteen Cu( i ) complexes of the general formula [Cu(PP)(LL)][BF 4 ], where PP is a phosphane ligand and LL represents an N,O-heteroaromatic bidentate ligand, has been synthesized and fully characterized by classical analytical and spectroscopic methods. Five complexes of this series were also characterized by single crystal X-ray diffraction studies. The cytotoxicity of all compounds was evaluated in breast (MCF7) and prostate (LNCap) human cancer cells and in a normal prostate cell line (RWPE). In general, all compounds showed higher cytotoxicity for the prostate cancer cells than for the breast cells, with IC 50 values in the range 0.2-2 μM after 24 h of treatment. The most cytotoxic compound, [Cu(dppe)(2-ap)][BF 4 ] ( 16 ), where dppe = 1,2-bis(diphenylphosphano) ethane and 2-ap = 2-acetylpyridine, showed a high level of cellular internalization, generation of intracellular ROS and activation of the cell death mechanism via apoptosis/necrosis. Owing to its high cytotoxic activity for LNCap cells, being 70-fold higher than that for normal prostate cells (RWPE), complex ( 16 ) was found to be the most promising for further research in prostate cancer models. Synthesis of a new family of Cu( i )-phosphane complexes with N,O-heteroaromatic ligands leads to the complexes showing impressive cytotoxicity against LNCap human prostate cancer cells allied to high selectivity than against RWPE non-tumoral prostate cells.
ISSN:1477-9226
1477-9234
DOI:10.1039/d0dt02157a