Synthesis and biological activity of 7-phenyl-6,9-dihydro-3H-pyrrolo[3,2-f]quinolin-9-ones: a new class of antimitotic agents devoid of aromatase activity

J Med Chem. 2006 Mar 23;49(6):1910-5. doi: 10.1021/jm0510676.

Abstract

The newly synthesized 7-phenyl-3H-pyrrolo[3,2-f]quinolinones 16-26 and previously 27 and 28 were assayed for their in vitro antiproliferative activity on tumor cell lines, and the lead compound 16 in vivo on a singenic hepatocellular carcinoma in Balb/c mice. Results from FACS, immunofluorescence microscopy analysis, tubulin polymerization assay, and tritiated water release assay for the CYP19 activity confirmed the new compounds as potential anticancer agents acting by tubulin depolymerization, but devoid of aromatase activity unlike their geometric [2,3-h] isomers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimitotic Agents / chemical synthesis*
  • Antimitotic Agents / chemistry
  • Antimitotic Agents / pharmacology
  • Aromatase / metabolism*
  • Biopolymers
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cytoskeleton / drug effects
  • Drug Screening Assays, Antitumor
  • Flow Cytometry
  • Humans
  • Mice
  • Microscopy, Fluorescence
  • Neoplasm Transplantation
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrroles / pharmacology
  • Quinolones / chemical synthesis*
  • Quinolones / chemistry
  • Quinolones / pharmacology
  • Structure-Activity Relationship
  • Transplantation, Isogeneic
  • Tritium
  • Tubulin / chemistry
  • Water / metabolism

Substances

  • 7-phenyl-6,9-dihydro-3H-pyrrolo(3,2-f)quinolin-9-one
  • Antimitotic Agents
  • Biopolymers
  • Pyrroles
  • Quinolones
  • Tubulin
  • Water
  • Tritium
  • Aromatase