Synthesis and mass spectroscopy kinetics of a novel ternary copper(II) complex with cytotoxic activity against cancer cells.
The X-ray structure of the [Cu(I-hip)(phen)2](+).(I-hip-).(H2O)7 complex (1) (where I-hipH is referred to o-iodohippuric acid and phen is 1,10-phenanthroline) and its binary synthetic intermediate [Cu(I-hip)2(H2O)3].(H2O)2 (2) have been solved and characterized by different techniques. This ternary [Cu(I-hip)(phen)2]+.(I-hip-).7H2O complex generates the copper(I) complex [Cu(phen)2]+ in aqueous solution without the addition of any external reductant, possibly by an intramolecular red-ox process in the presence of oxygen; the ESI-HRMS spectra (electrospray ionization-high resolution mass spectroscopy) detect these species and 24h after the solution, [Cu(phen)2]+ is the main product. The complex 1 is capable of cleaving DNA. To evaluate the biological properties, we carried out: cell culture, cell proliferation assays, cell cycle analysis, and electrophoresis (SDS-PAGE) and immunoblotting. Complex 1 induced apoptosis of A549 cells at low nanomolar and induced marked decreases of cancer cells at concentrations that did not change adipocyte survival. These data indicate that the parent complex is a potential anticancer drug.
Barceló-Oliver
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Departament de Química, Grup de Química Bioinorgànica i Bioorgànica, IUNICS, Universitat de les Illes Balears, Campus UIB, Carretera Valldemossa km. 7.5, Palma de Mallorca E-07122, Spain.
García-Raso
A
A
Terrón
A
A
Molins
E
E
Prieto
M J
MJ
Moreno
V
V
Martínez
J
J
Lladó
V
V
López
I
I
Gutiérrez
A
A
Escribá
P V
PV
D041721:3T3-L1 Cells; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006801:Humans; D007465:Iodohippuric Acid / Q000737:chemistry; D007700:Kinetics; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010618:Phenanthrolines / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D009942:Organometallic Compounds; D010618:Phenanthrolines; D007465:Iodohippuric Acid; D003300:Copper; C025205:1,10-phenanthroline