Isatin-Schiff base copper(II) complexes and their influence on cellular viability.
Some copper(II) complexes with isatin (isa) or imine ligands derived from isatin were prepared, characterized by analytical and spectroscopic techniques, and had their biological activity toward proliferation of two different cell types verified. These complexes exhibit keto-enolic equilibria in aqueous solution, very dependent of pH, although isolated in the solid state in one defined form, and this type of equilibrium was previously verified to be crucial for their catalytic activity in the oxidation of carbohydrates, through intermediary generation of reactive oxygen species. Herein, biological studies carried out with tumor cells of different origin such as human neuroblastoma (SH-SY5Y) and promonocytic (U937) cells showed that these compounds exert different toxicity. In particular, while compounds [Cu(isaen)(H(2)O)]ClO(4).2H(2)O 2, [Cu(isahist)(H(2)O)](ClO(4))(2)4 and [Cu(isa)(2)]ClO(4)6 are not toxic for both cell lines at the concentrations used in this study, compounds [Cu(isapn)](ClO(4))(2)1, [Cu(isaepy)(2)](ClO(4))(2).2H(2)O 3 and [Cu(isami)(H(2)O)]ClO(4)5 are cytotoxic, with the compound 3 being the most effective. In these compounds, isaen, isahist, isapn, isaepy and isami stand for imine ligands prepared by condensation of ethylenediamine (en), histamine (hist), 1,3-diaminopropane (pn), 2-aminoethylpyridine (epy), and 8-aminoquinoline (ami) with isatin (isa). Cells treated with these compounds were committed to the apoptotic program as evidenced by cytofluorimetric analyses of cell cycle. Moreover, the toxicity of compound 5 was equivalent for both cell lines while the compound 1 was almost not toxic at 24h for SH-SY5Y cells where only an arrest in G1 phase was observed. Compound 3 was more efficient in inducing cell death and also in this case a striking effect on U937 cells (apoptotic cells 68% compared with 11% of SH-SY5Y) was observed. Therefore, the results indicated that their activity seems to be cell type specific.
Cerchiaro
Giselle
G
Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, P.O. Box 26077, CEP 05513-970, São Paulo, SP, Brazil.
Aquilano
Katia
K
Filomeni
Giuseppe
G
Rotilio
Giuseppe
G
Ciriolo
Maria Rosa
MR
Ferreira
Ana Maria Da Costa
AM
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000737:chemistry*; D006801:Humans; D007510:Isatin / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D012545:Schiff Bases / Q000737:chemistry; D020298:U937 Cells
D009942:Organometallic Compounds; D012545:Schiff Bases; D003300:Copper; D007510:Isatin