Synthesis and biological evaluation of a new furo[2,3-h]quinolin-2(1H)-one

J Med Chem. 2002 Feb 28;45(5):1146-9. doi: 10.1021/jm010993r.

Abstract

A new furoquinolinone derivative, namely 4-hydroxymethyl-1,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one (HOFQ), was synthesized and its biological activity studied. By UVA activation, HOFQ induced strong antiproliferative effects in Ehrlich ascite cells, which lost their ability to transmit the tumor by transplantation. HOFQ exhibited poor genotoxicity and absence of skin phototoxicity. Actually, HOFQ sensitization forms DNA-protein cross-linkages but not interstrands cross-links. Therefore, HOFQ appears to be a new promising drug for PUVA photochemotherapy and photopheresis.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • CHO Cells
  • Carcinoma, Ehrlich Tumor / drug therapy
  • Cricetinae
  • Cross-Linking Reagents / chemical synthesis
  • Cross-Linking Reagents / chemistry
  • Cross-Linking Reagents / pharmacology
  • DNA / chemistry
  • DNA Damage
  • Drug Screening Assays, Antitumor
  • Escherichia coli / genetics
  • Furans / chemical synthesis*
  • Furans / chemistry
  • Furans / pharmacology
  • Guinea Pigs
  • Methoxsalen / pharmacology
  • Mice
  • Mutagenicity Tests
  • Neoplasm Transplantation
  • Quinolones / chemical synthesis*
  • Quinolones / chemistry
  • Quinolones / pharmacology
  • Skin / radiation effects
  • Structure-Activity Relationship
  • Tumor Cells, Cultured
  • Ultraviolet Rays

Substances

  • 4-hydroxymethyl-1,6,8-trimethylfuro(2,3-h)quinolin-2(1H)-one
  • Antineoplastic Agents
  • Cross-Linking Reagents
  • Furans
  • Quinolones
  • DNA
  • Methoxsalen