Novel all trans-retinoic Acid derivatives: cytotoxicity, inhibition of cell cycle progression and induction of apoptosis in human cancer cell lines

Molecules. 2015 May 7;20(5):8181-97. doi: 10.3390/molecules20058181.

Abstract

Owing to the pharmacological potential of ATRA (all trans-retinoic acid), a series of retinamides and a 1-(retinoyl)-1,3-dicyclohexylurea compound were prepared by reacting ATRA with long chain alkyl or alkenyl fatty amines by using a 4-demethylaminopyridine (DMAP)-catalyzed N,N¢-dicyclohexylcarbodiimide (DCC) coupling. The successful synthesis of the target compounds was demonstrated using a range of spectroscopic techniques. The cytotoxicity of the compounds was measured along with their ability to induce cell cycle arrest and apoptosis in human cancer cell lines MCF-7 (breast cancer) and HepG2 (liver cancer) and normal human cell line HEK293 (embryonic kidney). The results of cytotoxicity and flow cytometry data showed that the compounds had a moderate to strong effect against MCF-7 and HepG2 cells and were less toxic to HEK293 cells. N-oleyl-retinamide was found to be the most potent anticancer agent and was more effective against MCF-7 cells than HepG2 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects*
  • Breast Neoplasms / drug therapy
  • Cell Cycle Checkpoints / drug effects*
  • Cell Line
  • Cell Line, Tumor
  • Female
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms
  • MCF-7 Cells
  • Tretinoin / analogs & derivatives
  • Tretinoin / chemistry
  • Tretinoin / pharmacology*
  • Urea / analogs & derivatives
  • Urea / chemistry
  • Urea / pharmacology

Substances

  • Antineoplastic Agents
  • Tretinoin
  • Urea
  • retinamide
  • 1,3-dicyclohexylurea