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J Inorg Biochem ; 132: 77-91, 2014 Mar.
Article de Anglais | MEDLINE | ID: mdl-24287102

RÉSUMÉ

Four new molybdenocene complexes, Cp2Mo(l-ascorbato), Cp2Mo(6-O-palmitoyl-l-ascorbato), [Cp2Mo(ethyl maltolato)]Cl and Cp2Mo((2S)-2-amino-3-methyl-3-thiolato-butanoato), were synthesized and structurally characterized by standard analytical methods. The cytotoxicity of these complexes was assessed on colon HT-29 and breast MCF-7 cancer cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A higher cytotoxic activity was shown by all the new complexes on the MCF-7 cells over the Cp2MoCl2 complex. The complexes Cp2Mo(l-ascorbato), Cp2Mo(6-O-palmitoyl-l-ascorbato) and [Cp2Mo(ethyl maltolato)]Cl displayed a stronger cytotoxic activity on colon cancer HT-29 cell line, over the molybdenocene dichloride (Cp2MoCl2). In contrast, Cp2Mo((2S)-2-amino-3-methyl-3-thiolato-butanoato) exhibited proliferative properties on this cell line. Ubiquitin (Ub)-molybdenocene interactions were investigated using cyclic voltammetry, fluorescence quenching spectroscopy, circular dichroism (CD) and molecular modeling. The thermodynamic parameters (ΔH and ΔS) obtained using fluorescence quenching spectra and van't Hoff plot indicate the Ub-molybdenocene interactions are mainly hydrophobic. The CD data also support hydrophobic interactions with conformational changes in the Ub protein. Docking studies using molecular modeling revealed the amino acids involved in the Ub-molybdenocene interactions and corroborated the hydrophobic nature of the binding combined with hydrogen bonding.


Sujet(s)
Complexes de coordination , Modèles moléculaires , Composés organométalliques , Ubiquitine/composition chimique , Eau/composition chimique , Antinéoplasiques/synthèse chimique , Antinéoplasiques/composition chimique , Antinéoplasiques/toxicité , Tumeurs du sein/traitement médicamenteux , Lignée cellulaire tumorale , Survie cellulaire/effets des médicaments et des substances chimiques , Dichroïsme circulaire , Tumeurs du côlon/traitement médicamenteux , Complexes de coordination/synthèse chimique , Complexes de coordination/composition chimique , Complexes de coordination/toxicité , Femelle , Humains , Simulation de docking moléculaire , Composés organométalliques/composition chimique , Composés organométalliques/métabolisme , Composés organométalliques/toxicité , Solubilité , Spectrométrie de fluorescence , Ubiquitine/métabolisme , Ubiquitine/pharmacologie , Ubiquitine/toxicité
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