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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

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Abstract

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 (Cp2WCl2, 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 Cp2WCl2 < [Cp2W(ethyl maltolato)]Cl < [Cp2W(maltolato)]Cl < [Cp2W(kojato)]Cl, consistent with the hydrophobic interactions and the number of hydrogen bonds involved.

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Acknowledgments

E.M. acknowledges the NIH-MBRS SCORE program at the University of Puerto Rico Mayagüez for financial support via NIH-MBRS-SCORE program grant S06 GM008103-37. We are grateful to Jesús Olivero-Verbel from the University of Cartagena, Colombia, for allowing us to use the program SYBIL and for revising the manuscript.

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Authors and Affiliations

  1. Department of Chemistry, University of Puerto Rico, PO Box 9019, Mayagüez, PR, 00681, USA

    Moralba Domínguez-García, Carlos Ortega-Zúñiga & Enrique Meléndez

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  1. Moralba Domínguez-García
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  2. Carlos Ortega-Zúñiga
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  3. Enrique Meléndez
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Correspondence to Enrique Meléndez.

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Domínguez-García, M., Ortega-Zúñiga, C. & Meléndez, E. 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. J Biol Inorg Chem 18, 195–209 (2013). https://doi.org/10.1007/s00775-012-0964-2

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  • DOI: https://doi.org/10.1007/s00775-012-0964-2

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