One-Pot Synthesis of Coumarin-Indomethacin Hybrids as COX-2 Targeting Probes for Cancer Imaging

ChemMedChem. 2021 May 18;16(10):1660-1666. doi: 10.1002/cmdc.202100003. Epub 2021 Mar 9.

Abstract

Facile synthesis of 6- or 7-substituted coumarin-indomathacin hybrids (Coum-IDM) has been developed for specific cyclooxygenase-2 (COX-2) binding along with their intrinsic fluorescent properties. A mild and rapid condensation/dehydrative cyclization of 2-hydroxy benzaldehyde with activated indomethacin was carried out in one step under ultrasound irradiation. Coum-IDM4 was found to be the best of this series as it presented significant binding to COX-2 and exhibited higher fluorescent intensity in cancer cells than in normal cells. Therefore, in the light of drug development tools, this new hybrid system could be a potential targeted probe for COX-2-overexpressed inflammation and cancer-cell tracking.

Keywords: COX-2; cancer targeting; coumarin; cyclooxygenase; indomethacin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Survival / drug effects
  • Coumarins / chemistry
  • Coumarins / pharmacology*
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase 2 Inhibitors / chemical synthesis
  • Cyclooxygenase 2 Inhibitors / chemistry
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry
  • Fluorescent Dyes / pharmacology*
  • Humans
  • Indomethacin / chemistry
  • Indomethacin / pharmacology*
  • Molecular Docking Simulation
  • Molecular Structure
  • Optical Imaging*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Coumarins
  • Cyclooxygenase 2 Inhibitors
  • Fluorescent Dyes
  • coumarin
  • Cyclooxygenase 2
  • Indomethacin