Synthesis and biological evaluation of new tetrahydro-beta-carbolines as inhibitors of the mitotic kinesin Eg5.
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.
Sunder-Plassmann
Nils
N
University of Leipzig, Institute for Organic Chemistry, Johannisallee 29, 04103 Leipzig, Germany.
Sarli
Vasiliki
V
Gartner
Michael
M
Utz
Mathias
M
Seiler
Jeanette
J
Huemmer
Stefan
S
Mayer
Thomas U
TU
Surrey
Thomas
T
Giannis
Athanassios
A
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
D002243:Carbolines; C483533:HR22C16; D007211:Indoles; C088335:KIF11 protein, Xenopus; D009498:Neurotoxins; D010636:Phenols; D029867:Xenopus Proteins; C009804:tryptoline; D016547:Kinesins