title: 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.
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 (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.
authors.affiliation: Department of Chemistry, University of Puerto Rico, PO Box 9019, Mayagüez, PR, 00681, USA.
authors.forename: Moralba
authors.initials: M
authors.lastname: Domínguez-García
authors.affiliation: Department of Chemistry, University of Puerto Rico, PO Box 9019, Mayagüez, PR, 00681, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Ortega-Zúñiga
authors.affiliation: Department of Chemistry, University of Puerto Rico, PO Box 9019, Mayagüez, PR, 00681, USA. enrique.melendez@upr.edu.
authors.forename: Enrique
authors.initials: E
authors.lastname: Meléndez
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D012709:Serum Albumin; D012995:Solubility; D013050:Spectrometry, Fluorescence; D014414:Tungsten
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D009942:Organometallic Compounds; D012709:Serum Albumin; C406884:titanocene; D014414:Tungsten