RESUMO
In this work the synthesis and characterization of new gold(III) complexes with quinoline ligands are described. These complexes contain different steric and electronic properties of the donor atom at 8-position of the quinoline in order to modulate their stability and their biological activity. Their redox potential, stability in organic and aqueous solvents, and their biological activity in a panel of six different human tumor cell lines are also presented. In addition, interaction studies of the complexes with model biological molecules (pBR322 and L-acetyl-N-cysteine) were carried out, suggesting that their main target are proteins. From these studies, we have found that the gold(III) complex with an N-tosyl-8-aminoquinoline ligand is the most active complex in all the tumor cell lines, including the cisplatin resistant T-47D and WiDr cell lines. Moreover, this complex showed to be the most stable compound in DMSO and saline solution, even after several hours.
Assuntos
Antineoplásicos , Proliferação de Células/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Compostos Organoáuricos , Quinolinas , Células A549 , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Técnicas Eletroquímicas , Células HeLa , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Compostos Organoáuricos/síntese química , Compostos Organoáuricos/química , Compostos Organoáuricos/farmacologia , Quinolinas/síntese química , Quinolinas/química , Quinolinas/farmacologiaRESUMO
In this article, we report on the synthesis and the chemical and biological characterization of novel gold(III) complexes based on hydroxyl- or amino-quinoline ligands that are evaluated as prospective anticancer agents. To gain further insight into their reactivity and possible mode of action, their interactions with model proteins and standard nucleic acid molecules were investigated.
Assuntos
Antineoplásicos/síntese química , DNA/química , Complexo IV da Cadeia de Transporte de Elétrons/química , Compostos Organoáuricos/síntese química , Quinolinas/química , Sequência de Aminoácidos , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Humanos , Ligantes , Dados de Sequência Molecular , Compostos Organoáuricos/química , Compostos Organoáuricos/farmacologia , Compostos Organoáuricos/toxicidade , Ligação ProteicaRESUMO
The asymmetric synthesis of tricyclic compounds by the desymmetrization of cyclohexadienones is presented. The reaction tolerated a large variety of substituents at different positions of the cyclohexadienone, and heterocyclic rings of different sizes were accessible. Density functional theory calculations showed that the reaction proceeds through an asynchronous [4+2] cycloaddition.
Assuntos
Cicloexenos/química , Cristalografia por Raios X , EstereoisomerismoRESUMO
In this communication, we present the synthesis of new platinum complexes based on hydroxyquinoline ligands. We demonstrate the importance and the role of the halogen substitution as well as the chelation, which are essential structural characteristics for finding good cytotoxicities.
Assuntos
Antineoplásicos/farmacologia , Clioquinol/química , Halogênios/química , Hidroxiquinolinas/química , Compostos Organoplatínicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Ligantes , Modelos Moleculares , Estrutura Molecular , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/química , Relação Estrutura-AtividadeRESUMO
The use of a catalytic amount of platinum complexes (1 mol %) was found to be compatible with different organocatalysts (DABCO or the Jørgensen-Hayashi catalyst) that were used in the functionalization of various activated methylenes. By this method, a series of lactones with C-3 quaternary centers and substitution at C-5 were prepared.