Water soluble molybdenocene complexes: synthesis, cytotoxic activity and binding studies to ubiquitin by fluorescence spectroscopy, circular dichroism and molecular modeling.

Abstract

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.

• Authors: Xiomara Narváez-Pita, Carlos Ortega-Zuniga, Claudia Y Acevedo-Morantes, Belinda Pastrana, Jesus Olivero-Verbel, Wilson Maldonado-Rojas, Jaime E Ramírez-Vick, Enrique Meléndez
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 132 Pg. 77-91 (Mar 2014) ISSN: 1873-3344 [Electronic] United States
• PMID: 24287102 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Antineoplastic Agents
• Coordination Complexes
• Organometallic Compounds
• Ubiquitin
• molybdenocene dichloride
• Water

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, toxicity)
• Breast Neoplasms (drug therapy)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Circular Dichroism
• Colonic Neoplasms (drug therapy)
• Coordination Complexes (chemical synthesis, chemistry, toxicity)
• Female
• Humans
• Models, Molecular
• Molecular Docking Simulation
• Organometallic Compounds (chemistry, metabolism, toxicity)
• Solubility
• Spectrometry, Fluorescence
• Ubiquitin (chemistry, metabolism, pharmacology, toxicity)
• Water (chemistry)