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

J Inorg Biochem. 2014 Mar;132:77-91. doi: 10.1016/j.jinorgbio.2013.10.014. Epub 2013 Oct 29.

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.

Keywords: Anti-cancer drug; Docking; HT-29; MCF-7; Molybdenocene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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