New tungstenocenes containing 3-hydroxy-4-pyrone ligands: antiproliferative activity on HT-29 and MCF-7 cell lines and binding to human serum albumin studied by fluorescence spectroscopy and molecular modeling methods

• Published in: Journal of biological inorganic chemistry Vol. 18; no. 2; pp. 195 - 209
• Main Authors: Domínguez-García, Moralba, Ortega-Zúñiga, Carlos, Meléndez, Enrique
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-02-2013
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Binding Sites; Biochemistry; Biomedical and Life Sciences; Cell Proliferation - drug effects; Cell Survival - drug effects; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; HT29 Cells; Humans; Hydrogen Bonding; Hydrophobic and Hydrophilic Interactions; Inhibitory Concentration 50; Life Sciences; MCF-7 Cells; Microbiology; Models, Molecular; Molecular Docking Simulation; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Original Paper; Protein Binding; Serum Albumin; Solubility; Spectrometry, Fluorescence; Tungsten; Tungstenocene dichloride; Anticancer drug; Antitumor agent; HT-29; MCF-7
• ISSN: 0949-8257; 1432-1327
• DOI: 10.1007/s00775-012-0964-2

Three new water-soluble tungstenocene derivatives were synthesized and characterized using 3-hydroxy-4-pyrone ligands, which provide aqueous stability to the complexes. The antiproliferative activities of the complexes on HT-29 colon cancer and MCF-7 breast cancer cell lines were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and showed the new tungstenocene derivatives have higher antiproliferative action than tungstenocene dichloride (Cp
2
WCl
2
, where Cp is cyclopentadienyl). The binding interactions of the tungstenocenes with human serum albumin (HSA) were investigated using fluorescence spectroscopy and molecular modeling methods. Analysis of the fluorescence quenching spectra indicates that the tungstenocene complexes bind HSA by hydrophobic interactions and hydrogen bonding at fatty acid binding site 6 and drug binding site II. Docking studies provided a description of the hydrophobic interactions and hydrogen bonding by which the tungstenocenes become engaged with HSA. It was determined that the binding affinity of the tungstenoecenes for HSA is in the order Cp
2
WCl
2
 < [Cp
2
W(ethyl maltolato)]Cl < [Cp
2
W(maltolato)]Cl < [Cp
2
W(kojato)]Cl, consistent with the hydrophobic interactions and the number of hydrogen bonds involved.
Graphical abstract