title: [4-(imidazol-1-yl)thiazol-2-yl]phenylamines. A novel class of highly potent colchicine site binding tubulin inhibitors: synthesis and cytotoxic activity on selected human cancer cell lines.
abstract: Synthesis and cytotoxic activity in the submicromolar range of a series of [4-(imidazol-1-yl)thiazol-2-yl]phenylamines are described. Cell cycle dependent cytotoxicity on RKO human colon carcinoma cells with inducible expression of p27(kip1) and the influence on microtubule formation were investigated. Considering the significant correlation between the IC(50) values of tubulin polymerization inhibition, [(3)H]colchicine competition, and cytotoxicity of the investigated compounds, tubulin is the main cellular target. The inhibition of microtubule formation was shown to be mediated by interference with the colchicine binding site of tubulin. In depth analysis of the investigated compounds allowed the identification of modifications that altered the pharmacological profile of the compounds from a mitosis-inducing phenotype to a G1 cell cycle arresting phenotype.
authors.affiliation: Department of Pharmaceutical Chemistry I, University of Regensburg, D-93040 Regensburg, Germany. siavosh.mahboobi@chemie.uni-regensburg.de
authors.forename: Siavosh
authors.initials: S
authors.lastname: Mahboobi
authors.forename: Andreas
authors.initials: A
authors.lastname: Sellmer
authors.forename: Heymo
authors.initials: H
authors.lastname: Höcher
authors.forename: Emerich
authors.initials: E
authors.lastname: Eichhorn
authors.forename: Thomas
authors.initials: T
authors.lastname: Bär
authors.forename: Mathias
authors.initials: M
authors.lastname: Schmidt
authors.forename: Thomas
authors.initials: T
authors.lastname: Maier
authors.forename: Josef F
authors.initials: JF
authors.lastname: Stadlwieser
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Beckers
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003078:Colchicine / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000814:Aniline Compounds; D013844:Thiazoles; D014404:Tubulin; D050257:Tubulin Modulators; D003078:Colchicine