Cyclopalladated compounds as chemotherapeutic agents: Antitumor activity against a murine melanoma cell line

• Autor(a) principal: Rodrigues, Elaine Guadelupe [UNIFESP]
• Data de Publicação: 2003
• Outros Autores: Silva, Luiz S [UNIFESP], Fausto, D. M., Hayashi, M. S., Dreher, S., Santos, Edson Lucas dos [UNIFESP], Pesquero, Joao Bosco [UNIFESP], Travassos, Luiz Rodolpho [UNIFESP], Caires, ACF
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://repositorio.unifesp.br/handle/11600/27481; http://dx.doi.org/10.1002/ijc.11434
• topic: palladium; palladacycle-biphosphinic complexes; antitumor activity; B16F10 murine melanoma; apoptosis; chemotherapy

Palladacycle compounds obtained from N, N-dimethyl- I phenethylamine (dmpa), phenyl-2-pyridinyl-acetylene and 1-phenyl-3-N, N-dimethylamine-propine, respectively, were complexed to 1, 2 ethanebis (diphenylphosphine) (dppe) ligand to synthesize antitumor cyclopallaclated complexes that were tested in vitro and in vivo against syngeneic B16F10-Nex2 murine melanoma cells of low immunogenicity implanted subcutaneously in mice. Complexes were not toxic to mice injected 3 times i.p. with as much as 60 muM/animal/week. of 3 cyclopallaclated complexes that were inhibitory in vitro at low concentrations (< 1.25 muM), complex 7a was the most active in vivo, delaying tumor growth and prolonging animal survival. in vitro, binucleate complex 7a caused a collapse of respiratory activity with an abrupt decrease of extracellular acidification on short incubation (up to 100 min), followed by DNA degradation after 24 hr. the apoptosis-like reaction to this Pd-complex was not accompanied by increased levels of caspases I and 3. Complex 7a bound to a bacterial plasmid DNA, causing late conformational changes after 24 hr. Two other complexes with different C, N-cycles were also apoptotic and 2 binucleated ones were inactive. These results introduce the palladacycle-dppe complexes as promising antitumor drugs with exquisite structural specificities and for action in vivo and in vitro. (C) 2003 Wiley-Liss, Inc.