title: 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.affiliation: Department of Chemistry, University of Puerto Rico, P.O. Box 9000, Mayaguez 00681, Puerto Rico.
authors.forename: Xiomara
authors.initials: X
authors.lastname: Narváez-Pita
authors.affiliation: Department of Chemistry, University of Puerto Rico, P.O. Box 9000, Mayaguez 00681, Puerto Rico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Ortega-Zuniga
authors.affiliation: Engineering Science & Materials Department, University of Puerto Rico, P.O. Box 9000, Mayaguez 00681, Puerto Rico.
authors.forename: Claudia Y
authors.initials: CY
authors.lastname: Acevedo-Morantes
authors.affiliation: Department of Chemistry, University of Puerto Rico, P.O. Box 9000, Mayaguez 00681, Puerto Rico.
authors.forename: Belinda
authors.initials: B
authors.lastname: Pastrana
authors.affiliation: University of Cartagena, Environmental and Computational Chemistry Group, Campus of Zaragocilla, School of Pharmaceutical Sciences, Cartagena, Colombia.
authors.forename: Jesus
authors.initials: J
authors.lastname: Olivero-Verbel
authors.affiliation: University of Cartagena, Environmental and Computational Chemistry Group, Campus of Zaragocilla, School of Pharmaceutical Sciences, Cartagena, Colombia.
authors.forename: Wilson
authors.initials: W
authors.lastname: Maldonado-Rojas
authors.affiliation: Engineering Science & Materials Department, University of Puerto Rico, P.O. Box 9000, Mayaguez 00681, Puerto Rico.
authors.forename: Jaime E
authors.initials: JE
authors.lastname: Ramírez-Vick
authors.affiliation: Department of Chemistry, University of Puerto Rico, P.O. Box 9000, Mayaguez 00681, Puerto Rico. Electronic address: enrique.melendez@upr.edu.
authors.forename: Enrique
authors.initials: E
authors.lastname: Meléndez
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D003110:Colonic Neoplasms / Q000188:drug therapy; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D005260:Female; D006801:Humans; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009942:Organometallic Compounds / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D012995:Solubility; D013050:Spectrometry, Fluorescence; D025801:Ubiquitin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D014867:Water / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D009942:Organometallic Compounds; D025801:Ubiquitin; C471975:molybdenocene dichloride; D014867:Water
keywords: Anti-cancer drug; Docking; HT-29; MCF-7; Molybdenocene