title: The Mechanism of the Interactions of Pironetin Analog/Combretastatin A-4 Hybrids with Tubulin.
abstract: We here report an investigation of the interactions with tubulin of two types of molecules of a hybrid structural type consisting in a combretastatin A-4 moiety and a simplified pironetin fragment. The cytotoxicities of the molecules on two reference tumoral cell lines were measured. In addition, the effects of the compounds on the cell cycle and on microtubule assembly were observed. The dynamics of microtubule polymerization was investigated by means of immunofluorescence assays. It was thus established that at least some of the compounds under study exert their cytotoxic action by means of interaction with tubulin.
authors.affiliation: Departamento de Química Inorgánica y Orgánica, Universidad Jaume I, Castellón, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Torijano-Gutiérrez
authors.affiliation: Departamento de Química Inorgánica y Orgánica, Universidad Jaume I, Castellón, Spain.
authors.forename: Concepción
authors.initials: C
authors.lastname: Vilanova
authors.affiliation: Departamento de Química Inorgánica y Orgánica, Universidad Jaume I, Castellón, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Díaz-Oltra
authors.affiliation: Departamento de Química Inorgánica y Orgánica, Universidad Jaume I, Castellón, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Murga
authors.affiliation: Departamento de Química Inorgánica y Orgánica, Universidad Jaume I, Castellón, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Falomir
authors.affiliation: Departamento de Química Inorgánica y Orgánica, Universidad Jaume I, Castellón, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Carda
authors.affiliation: CIB, CSIC, Madrid, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Redondo-Horcajo
authors.affiliation: CIB, CSIC, Madrid, Spain.
authors.forename: José Fernando
authors.initials: JF
authors.lastname: Díaz
authors.affiliation: CIB, CSIC, Madrid, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Barasoain
authors.affiliation: Departamento de Química Orgánica, Universidad Valencia, Burjassot, Spain.
authors.forename: Juan Alberto
authors.initials: JA
authors.lastname: Marco
mesh_terms: D001665:Binding Sites; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D019073:HT29 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D058105:Polymerization; D011485:Protein Binding; D011487:Protein Conformation; D011753:Pyrones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013267:Stilbenes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D050257:Tubulin Modulators / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D010446:Peptide Fragments; D011753:Pyrones; D013267:Stilbenes; D014404:Tubulin; D050257:Tubulin Modulators; C088446:pironetin; C058728:fosbretabulin
keywords: Combretastatin A-4 derivatives; Cytotoxic compounds; Hybrid molecules; Microtubules; Pironetin