کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1316201 | 1499455 | 2014 | 15 صفحه PDF | دانلود رایگان |
• Ascorbato ligands on molybdenocene increases the anti-proliferative activity
• Ubiquitin-molybdenocene interactions are mainly hydrophobic
• Ubiquitin may serve as a drug reservoir
• CD titration studies confirm the Ub molybdenocene interactions are mainly hydrophobic
• Docking studies corroborate the intermolecular interactions are mainly hydrophobic
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.
Four new molybdenocene derivatives with various degrees of hydrophobic character were synthesized. A higher cytotoxic activity was shown by all the new complexes on the MCF-7 cells over the Cp2MoCl2 complex. The thermodynamic parameters indicate the ubiquitin–molybdenocene interactions are mainly hydrophobic.Figure optionsDownload as PowerPoint slide
Journal: Journal of Inorganic Biochemistry - Volume 132, March 2014, Pages 77–91