title: Structure-activity relationships of carboline and carbazole derivatives as a novel class of ATP-competitive kinesin spindle protein inhibitors.
abstract: The kinesin spindle protein (KSP) is a mitotic kinesin involved in the establishment of a functional bipolar mitotic spindle during cell division. It is considered to be an attractive target for cancer chemotherapy with reduced side effects. Based on natural product scaffold-derived fused indole-based inhibitors and known biphenyl-type KSP inhibitors, various carboline and carbazole derivatives were synthesized and biologically evaluated. β-Carboline and lactam-fused carbazole derivatives exhibited remarkably potent KSP inhibitory activity and mitotic arrest in prometaphase with formation of an irregular monopolar spindle. The planar tri- and tetracyclic analogs inhibited KSP ATPase in an ATP-competitive manner just like biphenyl-type inhibitors.
authors: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors: Tomoki
authors: T
authors: Takeuchi
authors: Shinya
authors: S
authors: Oishi
authors: Toshiaki
authors: T
authors: Watanabe
authors: Hiroaki
authors: H
authors: Ohno
authors: Jun-ichi
authors: J
authors: Sawada
authors: Kenji
authors: K
authors: Matsuno
authors: Akira
authors: A
authors: Asai
authors: Naoya
authors: N
authors: Asada
authors: Kazuo
authors: K
authors: Kitaura
authors: Nobutaka
authors: N
authors: Fujii