title: Docking study of ligands into the colchicine binding site of tubulin.
abstract: Cancer is a major cause of mortality in developed countries, following only cardiovascular diseases. Death of cancerous cells can be achieved by stopping mitosis and the antimitotic class of drugs formed by the spindle poisons can be used for this purpose. Their role is to disorganize the mitotic spindle by targeting its main constituent, the microtubules, themselves made of heterodimers of alpha and beta-tubulin. They disrupt the dynamics of the microtubules either by stabilizing them, as do paclitaxel or epothilones, or destabilizing them, as do colchicine. The binding site of colchicine seems to lie between the two units of the tubulin dimer. Here, we report on the characterization of this site by the docking of a series of reference compounds, and the subsequent docking of ligands prepared in our laboratory.
authors.affiliation: Laboratoire de Chimie Thérapeutique, Faculté des Sciences Pharmaceutiques et Biologiques, 59006 Lille Cedex, France.
authors.forename: Amaury
authors.initials: A
authors.lastname: Farce
authors.forename: Cedric
authors.initials: C
authors.lastname: Loge
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gallet
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lebegue
authors.forename: Pascal
authors.initials: P
authors.lastname: Carato
authors.forename: Philippe
authors.initials: P
authors.lastname: Chavatte
authors.forename: Pascal
authors.initials: P
authors.lastname: Berthelot
authors.forename: Daniel
authors.initials: D
authors.lastname: Lesieur
mesh_terms: D000818:Animals; D050256:Antimitotic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D003078:Colchicine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D008024:Ligands; D051379:Mice; D015394:Molecular Structure; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D021281:Quantitative Structure-Activity Relationship; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry / Q000187:drug effects*
chemical_list: D050256:Antimitotic Agents; D008024:Ligands; D014404:Tubulin; D003078:Colchicine