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Cyclopalladated compounds as chemotherapeutic agents: Antitumor activity against a murine melanoma cell line
Author(s) -
Rodrigues Elaine G.,
Silva Luiz S.,
Fausto Daniela M.,
Hayashi Marina S.,
Dreher Simone,
Santos Edson L.,
Pesquero João B.,
Travassos Luiz R.,
Caires Antonio C.F.
Publication year - 2003
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.11434
Subject(s) - in vivo , in vitro , apoptosis , chemistry , pharmacology , cell culture , melanoma , microbiology and biotechnology , stereochemistry , biology , biochemistry , cancer research , genetics
Palladacycle compounds obtained from N, N‐dimethyl‐1‐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 cyclopalladated 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 μM/animal/week. Of 3 cyclopalladated complexes that were inhibitory in vitro at low concentrations (<1.25 μM), 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 1 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. © 2003 Wiley‐Liss, Inc.