Kinesin spindle protein (KSP) inhibitors with 2,3-fused indole scaffolds.
Mitotic kinesin spindle protein (KSP) is involved in the assembly of the bipolar spindle during cell division. On the basis of a common 2,3-fused indole substructure within the complex frameworks of terpendole E and other KSP inhibitors, the carbazoles with a bulky alkyl group were identified as a novel KSP inhibitory scaffold. Additionally, among several naturally occurring cell growth inhibitors with 2,3-fused indole structures, beta-carboline alkaloids, harman and harmine, showed moderate inhibition of KSP.
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. soishi@pharm.kyoto-u.ac.jp
Shinya
S
Oishi
Toshiaki
T
Watanabe
Jun-Ichi
J
Sawada
Akira
A
Asai
Hiroaki
H
Ohno
Nobutaka
N
Fujii
D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002227:Carbazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D000470:Alkaloids; D002227:Carbazoles; C470243:KIF11 protein, human; D016547:Kinesins