RESUMO
We have synthesized and characterized a panel of new binuclear mixed valence Cu(I,II) complexes containing substituted 2-alkylthio-5-arylmethylene-4H-imidazolin-4-ones with unusual structure. These complexes are shown to be cytotoxic for various cell lines. We have found that these compounds did not intercalate DNA, inhibited number of polymerases (telomerase predominantly), accumulated in the cell nucleus, and caused DNA degradation. Preliminary studies revealed that lead compound inhibited human breast adenocarcinoma growth in mice model.
Assuntos
Antineoplásicos/farmacologia , Cobre/química , Neoplasias Experimentais/tratamento farmacológico , Compostos Organometálicos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Dano ao DNA , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HEK293 , Células Hep G2 , Humanos , Células MCF-7 , Camundongos , Camundongos Endogâmicos C57BL , Modelos Moleculares , Estrutura Molecular , Neoplasias Experimentais/patologia , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Relação Estrutura-AtividadeRESUMO
In a series of studies in SPF and conventional guinea pigs, various adjuvants (larifan, polyoxidonium-PO, natrium thiosulphate-NT, TNF-ß and Ribi adjuvant system-RAS) were evaluated for their ability to enhance immune responses to the live brucellosis vaccine, Brucella abortus strain 82-PS (penicillin-sensitive). Combining adjuvants with S82-PS increased synthesis of antibodies against rough (R) and smooth (S) Brucella antigens. Dynamics and levels of antibodies differed dependent upon the adjuvant. Adjuvants enhanced cell-mediated responses to S82-PS, and phagocytosis by macrophages. Humoral and cellular immune responses stimulated by the adjuvants correlated with increased vaccine protection against experimental challenge. The highest protection was demonstrated by combining TNF-ß or PO with S82-PS. Our data demonstrates the potential of adjuvants to improve immunogenic properties of live brucellosis vaccines.