Azetidinone-retinoid hybrids: synthesis and differentiative effects

Eur J Med Chem. 2013;70:857-63. doi: 10.1016/j.ejmech.2013.09.057. Epub 2013 Oct 12.

Abstract

As a part of a systematic investigation on the synthesis and biological activities of new β-lactam compounds, we examined β-lactam candidates 1, 2E and 2Z and their ability to induce cell proliferation or differentiation. Azetidinone 1 was chosen for its activity (previously evaluated) as selective HDAC8 inhibitor, whereas β-lactams 2E and 2Z were designed to have a hybrid retinoid-azetidinone structure, de novo synthesized and fully characterized. Biological activities were determined in cellular assays on neuroblastoma cells SH-SY5Y. Azetidinone 1, 2E and 2Z led to a moderate effect in decreasing SH-SY5Y cell proliferation and β-lactams 2E and 2Z induced an early stage differentiation. The present results uncovered a new role of specifically designed β-lactam compounds in epigenetic regulation.

Keywords: Cell differentiation; Epigenetic regulation; HDAC inhibitors; Retinoids; Synthesis; β-Lactams.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Azetidines / chemistry
  • Azetidines / pharmacology*
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Retinoids / chemistry
  • Retinoids / pharmacology*
  • Structure-Activity Relationship

Substances

  • 2-azetidinone
  • Antineoplastic Agents
  • Azetidines
  • Retinoids