Related Experiment Video

Updated: Sep 1, 2025

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

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New 4-thiazolidinone-based molecules Les-2769 and Les-3266 as possible PPARγ modulators

Monika Bar1, Bartosz Skóra1, Anna Tabęcka-Łonczyńska1

  • 1Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225 Rzeszow, Poland.

Bioorganic Chemistry
|August 11, 2022
PubMed

Insights

Two novel 4-thiazolidinone derivatives, Les-2769 and Les-3266, show anticancer effects in vitro. Les-3266

Area of Science:

  • Pharmacology
  • Oncology
  • Molecular Biology

Background:

  • Cancer drug resistance necessitates novel therapeutic agents.
  • 4-Thiazolidinones exhibit known in vitro cytotoxicity against cancer cells.
  • Investigating new derivatives for anticancer potential is crucial.

Purpose of the Study:

  • To evaluate the PPARγ-dependent cytotoxicity of Les-2769 and Les-3266.
  • To assess the impact of these compounds on normal fibroblasts (BJ) and squamous cell carcinoma (SCC-15) in vitro.
  • To elucidate the potential mechanism of action involving PPARγ.

Main Methods:

  • In vitro cytotoxicity assays measuring metabolic activity, LDH release, and caspase-3 activity.
  • Co-treatment experiments with PPARγ agonists/antagonists.
  • Gene expression analysis (PPARγ, KI67, NF-κB).
  • Molecular docking simulations.

Main Results:

  • Les-2769 and Les-3266 demonstrated dose-dependent cytotoxicity in SCC-15 and BJ cells.
  • Les-3266's effects were modulated by PPARγ agonists/antagonists, suggesting pathway involvement.
  • Both compounds increased PPARγ mRNA expression, similar to rosiglitazone.
  • Molecular docking supported potential PPARγ agonistic activity for both compounds.

Conclusions:

  • Les-2769 and Les-3266 exhibit in vitro anticancer effects against SCC-15 cells.
  • The mechanism of Les-3266 likely involves the PPARγ receptor pathway.
  • Further investigation into the PPARγ interaction is warranted for therapeutic development.
Keywords:
4-thiazolidinonesAgonistAntagonistAnti-tumor activityCytotoxicityPPARγ

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