RESUMO
In this paper, citronellal, vanillin and pyridoxal thiosemicarbazones were modified with polar substituents, namely ethylmorpholine and glucose, to increase their polarity and compare the effects of these moieties on their biological activity. Altogether, nine ligands were synthesized and for each of them also their copper(II) and nickel(II) complexes were prepared and used for the biological tests. Eventually, assays on proliferation inhibition were conducted using leukemic cell line U937, already used as a model for previous citronellal thiosemicarbazone tests. Biological tests were also performed on solid tumor cell line HT29. From the first screenings, two of the metal complexes showed remarkable interesting properties, and, therefore, were also tested for histosensitivity.
Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Tiossemicarbazonas/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Cobre/química , Humanos , Ligantes , Estrutura Molecular , Níquel/química , Tiossemicarbazonas/síntese química , Tiossemicarbazonas/químicaRESUMO
A series of quinoline-2-carboxaldehyde thiosemicarbazones and their copper(II) and nickel(II) complexes were synthesized and characterized. In all complexes the ligands are in the E configuration with respect to the imino bond and behave as terdentate. The copper(II) complexes form square planar derivatives with one molecule of terdentate ligand and chloride ion. A further non-coordinated chloride ion compensates the overall charge. Nickel(II) ions form instead octahedral complexes with two ligands for each metal ion, independently from the stoichiometric metal:ligand ratio used in the synthesis. Ligands and complexes were tested for their antiproliferative properties on histiocytic lymphoma cell line U937. Copper(II) derivatives are systematically more active than the ligands and the nickel complexes. All copper derivatives result in inhibiting topoisomerase IIa in vitro. Computational methods were used to propose a model to explain the different extent of inhibition presented by these compounds. The positive charge of the dissociated form of the copper complexes may play a key role in their action.
Assuntos
Aldeídos/química , Cobre/química , DNA Topoisomerases Tipo II/metabolismo , Níquel/química , Compostos Organometálicos/farmacologia , Quinolinas/química , Tiossemicarbazonas/química , Inibidores da Topoisomerase II/farmacologia , Sequência de Aminoácidos , Linhagem Celular Tumoral , DNA Topoisomerases Tipo II/química , Humanos , Simulação de Acoplamento Molecular , Dados de Sequência Molecular , Compostos Organometálicos/síntese química , Ligação Proteica , Inibidores da Topoisomerase II/síntese químicaRESUMO
This paper reports the syntheses and characterization of ethylmorpholine substituted citronellal thiosemicarbazone copper(II) and nickel(II) metal complexes. The compounds were characterized through elemental analyses and spectroscopic (IR, UV-Vis, NMR, MS) methods. The X-ray analysis of the two complexes shows that both Ni and Cu derivatives present a square planar coordination, where the coordinating homologous donor atoms bind in trans to each other. The compounds were tested for their biological activity after determination of their octanol-saline partition coefficients, followed by their radical scavenging properties. Eventually the complexes were tested for their proliferation inhibition on human histiocytic lymphoma U937 cell line. The GI(50) values resulted to be 2.3microM for the copper derivative and 12.3microM for the nickel derivative.
