Synthesis and biological evaluation of a cyclic ether fluorinated noscapine analog

Bioorg Med Chem. 2006 Dec 15;14(24):8352-8. doi: 10.1016/j.bmc.2006.09.012. Epub 2006 Sep 27.

Abstract

We present here a novel semi-synthetic cyclic ether fluorinated noscapine analog (CEFNA) that shows potent antiproliferative and anticancer activity in both hormone-responsive (MCF-7) and hormone non-responsive (MDA-MB-231) breast cancer cells. Interestingly, it is also effective against MCF-7/Adr, an adriamycin-resistant variant of MCF-7 cells. Immunofluorescence experiments showed numerous micronuclei, indicative of apoptotic cell death triggered by this novel analog. Mechanistically, CEFNA exerts a strong antimitotic effect as revealed by cell-cycle studies that show a dose-dependent increase in G2/M population preceding a rising sub-G1 population, suggesting apoptosis.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibiotics, Antineoplastic / adverse effects
  • Antitussive Agents / chemical synthesis*
  • Antitussive Agents / chemistry
  • Antitussive Agents / pharmacology*
  • Apoptosis / drug effects
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Cell Cycle / drug effects
  • Doxorubicin / adverse effects
  • Drug Resistance, Neoplasm
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Noscapine / chemical synthesis*
  • Noscapine / chemistry
  • Noscapine / pharmacology*
  • Spindle Apparatus / drug effects
  • Tumor Cells, Cultured / drug effects

Substances

  • Antibiotics, Antineoplastic
  • Antitussive Agents
  • Doxorubicin
  • Noscapine