title: Synthesis and biological evaluation of new tetrahydro-beta-carbolines as inhibitors of the mitotic kinesin Eg5.
abstract: The mitotic kinesin Eg5 (or KSP) is a crucial player in the development and function of the mitotic spindle. Inhibition of this protein leads to cell cycle arrest and apoptosis without interfering with other microtubule-dependent processes. Therefore, it is a potential target in cancer therapy. Here, we report the synthesis and biological evaluation of a small library of molecules based on the structure of the known Eg5 inhibitor HR22C16. One of these derivatives (compound trans-24) proved to be a potent and specific Eg5 inhibitor.
authors.affiliation: University of Leipzig, Institute for Organic Chemistry, Johannisallee 29, 04103 Leipzig, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Sunder-Plassmann
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Sarli
authors.forename: Michael
authors.initials: M
authors.lastname: Gartner
authors.forename: Mathias
authors.initials: M
authors.lastname: Utz
authors.forename: Jeanette
authors.initials: J
authors.lastname: Seiler
authors.forename: Stefan
authors.initials: S
authors.lastname: Huemmer
authors.forename: Thomas U
authors.initials: TU
authors.lastname: Mayer
authors.forename: Thomas
authors.initials: T
authors.lastname: Surrey
authors.forename: Athanassios
authors.initials: A
authors.lastname: Giannis
mesh_terms: D000818:Animals; D002243:Carbolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000235:genetics; D008938:Mitosis / Q000187:drug effects*; D015394:Molecular Structure; D009498:Neurotoxins / Q000138:chemical synthesis / Q000494:pharmacology; D010636:Phenols / Q000737:chemistry; D029867:Xenopus Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D002243:Carbolines; C483533:HR22C16; D007211:Indoles; C088335:KIF11 protein, Xenopus; D009498:Neurotoxins; D010636:Phenols; D029867:Xenopus Proteins; C009804:tryptoline; D016547:Kinesins