Kinesin spindle protein (KSP) inhibitors with 2,3-fused indole scaffolds

J Med Chem. 2010 Jul 8;53(13):5054-8. doi: 10.1021/jm100476d.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemical synthesis
  • Alkaloids / chemistry
  • Alkaloids / pharmacology
  • Carbazoles / chemical synthesis
  • Carbazoles / chemistry*
  • Carbazoles / pharmacology*
  • Cell Proliferation / drug effects
  • HeLa Cells
  • Humans
  • Inhibitory Concentration 50
  • Kinesins / antagonists & inhibitors*
  • Kinesins / metabolism
  • Mitosis / drug effects
  • Spindle Apparatus / drug effects
  • Spindle Apparatus / metabolism
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Carbazoles
  • KIF11 protein, human
  • Kinesins