Tubulin binding, protein-bound conformation in solution, and antimitotic cellular profiling of noscapine and its derivatives

J Med Chem. 2012 Mar 8;55(5):1920-5. doi: 10.1021/jm200848t. Epub 2012 Feb 27.

Abstract

Noscapine and its 7-hydroxy and 7-amino derivatives were characterized for their binding to tubulin. A solution NMR structure of these compounds bound to tubulin shows that noscapine and its 7-aniline derivative do not compete for the same binding site nor does its small molecule crystal structure match its tubulin-bound conformation. These compounds were also tested for their antiproliferative effects on a panel hepatocellular carcinoma cell lines.

MeSH terms

  • Aniline Compounds / chemical synthesis*
  • Aniline Compounds / pharmacology
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Binding Sites
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Crystallography, X-Ray
  • Drug Screening Assays, Antitumor
  • Fluorescence
  • Humans
  • Magnetic Resonance Spectroscopy
  • Molecular Conformation
  • Noscapine / analogs & derivatives*
  • Noscapine / chemical synthesis*
  • Noscapine / pharmacology
  • Protein Binding
  • Solutions
  • Structure-Activity Relationship
  • Tubulin / chemistry*
  • Tubulin Modulators / chemical synthesis*
  • Tubulin Modulators / pharmacology

Substances

  • Aniline Compounds
  • Antineoplastic Agents
  • Solutions
  • Tubulin
  • Tubulin Modulators
  • Noscapine