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Synthesis and Antiproliferative Effect of Halogenated Coumarin Derivatives

Tinuccia Dettori1, Giuseppina Sanna1, Andrea Cocco2

  • 1Department of Biomedical Sciences, University of Cagliari, University Campus, 09042 Monserrato, CA, Italy.

Molecules (Basel, Switzerland)
|December 23, 2022
PubMed

Insights

New halogenated coumarin derivatives show antiproliferative effects against thyroid cancer cells. Compounds 2h and 2k induce apoptosis and alter cell cycle, with varying impacts on reactive oxygen species (ROS).

Area of Science:

  • Medicinal Chemistry
  • Cancer Biology
  • Molecular Pharmacology

Background:

  • Halogenated coumarin derivatives are explored for their potential anticancer properties.
  • Thyroid cancer remains a significant health concern, necessitating novel therapeutic strategies.
  • Understanding the molecular mechanisms of antiproliferative agents is crucial for drug development.

Purpose of the Study:

  • To synthesize and evaluate 6- and 6,8-halocoumarin derivatives as potential antiproliferative agents.
  • To investigate the molecular mechanisms underlying the cytotoxic effects of these compounds, including apoptosis, cell cycle, and oxidative stress.
  • To identify specific halocoumarin derivatives with potent activity against thyroid cancer cells.

Main Methods:

  • Synthesis of 6- and 6,8-halocoumarin derivatives.
  • Cytotoxicity assessment using the MTT assay against various tumor and normal cell lines.
  • Apoptosis assays, cell cycle analysis, reactive oxygen species (ROS) measurements, and reduced glutathione analysis to elucidate mechanisms of action.

Main Results:

  • Compounds 6,8-dibromo-2-oxo-2H-chromene-3-carbonitrile (2h) and 6,8-diiodo-2-oxo-2H-chromene-3-carbonitrile (2k) demonstrated the most significant antiproliferative activity against TPC-1 thyroid cancer cells.
  • Both 2h and 2k induced apoptosis in TPC-1 cells.
  • Treatment with 2h and 2k led to a G2/M phase cell cycle arrest and a decrease in the S phase.
  • Diiodocoumarin 2k significantly increased ROS levels, while dibromocoumarin 2h decreased ROS in a dose- and time-dependent manner.

Conclusions:

  • Halogenated coumarin derivatives, particularly 2h and 2k, show promise as antiproliferative agents against thyroid cancer.
  • The antiproliferative effects are mediated through the induction of apoptosis, cell cycle modulation, and alterations in oxidative stress.
  • Further investigation into these compounds may lead to the development of novel thyroid cancer therapeutics.
Keywords:
ROSTPC-1 cellsantiproliferative activityapoptosiscoumarins

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