Design, synthesis and anticancer evaluation of novel tetrahydroquinoline derivatives containing sulfonamide moiety

Eur J Med Chem. 2009 Oct;44(10):4211-7. doi: 10.1016/j.ejmech.2009.05.017. Epub 2009 May 24.

Abstract

Sulfonamides poses many types of biological activities and have recently been reported to show substantial antitumor activity in vitro and/or in vivo. There are a variety of mechanisms for the anticancer activity and the most prominent of these is through the inhibition of carbonic anhydrase isozymes. The present work reports the synthesis of some novel quinoline and pyrimido[4,5-b]quinoline derivatives bearing a substituted or unsubstituted sulfonamide moiety. The design of the structures of these compounds complies with the general pharmacophore of the sulfonamide compounds that act as carbonic anhydrase (CA) inhibitors as this may play a role in their anticancer activity. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against breast cancer cell line (MCF7). Most of the screened compounds showed interesting cytotoxic activities compared to a reference drug.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy
  • Carbonic Anhydrase II / chemistry
  • Carbonic Anhydrase II / metabolism
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Catalytic Domain
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Models, Molecular
  • Protein Binding
  • Quinolines / chemical synthesis
  • Quinolines / chemistry*
  • Quinolines / pharmacology*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacology*

Substances

  • Antineoplastic Agents
  • Carbonic Anhydrase Inhibitors
  • Quinolines
  • Sulfonamides
  • Carbonic Anhydrase II