Cyclopalladated compounds as chemotherapeutic agents: antitumor activity against a murine melanoma cell line
| Autor: | Luiz R. Travassos, Luiz S. Silva, Acf Caires, D. M. Fausto, M. S. Hayashi, Edson Lucas dos Santos, João Bosco Pesquero, S. Dreher, Elaine G. Rodrigues |
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| Přispěvatelé: | Universidade Federal de São Paulo (UNIFESP), Univ Mogi Cruzes |
| Rok vydání: | 2003 |
| Předmět: |
Male
Cancer Research Melanoma Experimental Antineoplastic Agents Apoptosis chemotherapy Mice Oxygen Consumption In vivo Tumor Cells Cultured Animals antitumor activity B16F10 murine melanoma Caspase palladacycle-biphosphinic complexes biology Immunogenicity apoptosis Biological activity DNA Neoplasm palladium Ligand (biochemistry) Molecular biology In vitro Mice Inbred C57BL Oncology Cell culture Immunology biology.protein Palladium |
| Zdroj: | Repositório Institucional da UNIFESP Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
| ISSN: | 0020-7136 |
| Popis: | 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. Universidade Federal de São Paulo, Unidade Oncol Expt, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, Brazil Univ Mogi Cruzes, CIIB, São Paulo, Brazil Universidade Federal de São Paulo, Dept Biofis, São Paulo, Brazil Universidade Federal de São Paulo, Unidade Oncol Expt, Dept Microbiol Immunol & Parasitol, BR-04023062 São Paulo, Brazil Universidade Federal de São Paulo, Dept Biofis, São Paulo, Brazil Web of Science |
| Databáze: | OpenAIRE |
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