The Mechanism of the Interactions of Pironetin Analog/Combretastatin A‐4 Hybrids with Tubulin

descriptionPublicationkeyboard_double_arrow_right Article 17 Jun 2015 English Publisher:WileyJournal:Archiv der Pharmazie, volume 348, pages 541-547 (issn: 0365-6233, eissn: 1521-4184,

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Authors: Torijano-Gutiérrez, Sandra; Vilanova, Concepción; Díaz-Oltra, Santiago; Murga, Juan; Falomir, Eva; Carda, Miguel; Redondo-Horcajo, Mariano; +3 Authors

doi: 10.1002/ardp.201500106

pmid: 26085125

handle: 10261/251448

The Mechanism of the Interactions of Pironetin Analog/Combretastatin A‐4 Hybrids with Tubulin

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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.

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Keywords

Cell Survival, Protein Conformation, Microtubules, Polymerization, Inhibitory Concentration 50, Structure-Activity Relationship, Combretastatin A-4 derivatives, Cytotoxic compounds, Hybrid molecules, Microtubules, Pironetin, Tubulin, Cytotoxic compounds, Stilbenes, Combretastatin A-4 derivatives, Humans, Pironetin, Binding Sites, Dose-Response Relationship, Drug, Cell Cycle, Hybrid molecules, Peptide Fragments, Tubulin Modulators, Pyrones, Drug Design, HT29 Cells, Protein Binding

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