Identification of novel and improved antimitotic agents derived from noscapine

J Med Chem. 2005 Nov 17;48(23):7096-8. doi: 10.1021/jm050674q.

Abstract

Analogues of the natural product noscapine were synthesized and their potential as antitumor agents evaluated. The discovery of a novel regioselective O-demethylation facilitated the synthesis of the potent aniline 6, which arrests mammalian cells in the G2/M phase of the cell cycle at 0.1 microM and also affects tubulin polymerization. Aniline 6 is orally bioavailable and is 250-fold more potent than noscapine in reducing cell proliferation in rapidly dividing cells.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / pharmacology
  • Biopolymers
  • Cell Line
  • Drug Screening Assays, Antitumor
  • G2 Phase / drug effects
  • HeLa Cells
  • Humans
  • Mice
  • Microtubules / drug effects
  • Noscapine / analogs & derivatives*
  • Noscapine / chemical synthesis*
  • Noscapine / pharmacokinetics
  • Noscapine / pharmacology
  • Stereoisomerism
  • Tubulin / chemistry
  • Tubulin Modulators / chemical synthesis
  • Tubulin Modulators / chemistry

Substances

  • Antineoplastic Agents
  • Biopolymers
  • Tubulin
  • Tubulin Modulators
  • Noscapine