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.
Ebtesam Saad Al-Sheddi  1 ,  Mai Mohammad Al-Oqail  2 ,  Quaiser Saquib  3  4 ,  Maqsood Ahmed Siddiqui  5  6 ,  Javed Musarrat  7  8 ,  Abdulaziz Ali Al-Khedhairy  9 ,  Nida Nayyar Farshori  10
Affiliations
  • 1. Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia. [email protected].
  • 2. Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia. [email protected].
  • 3. Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. [email protected].
  • 4. Al-Jeraisy Chair for DNA Research, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. [email protected].
  • 5. Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. [email protected].
  • 6. Al-Jeraisy Chair for DNA Research, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. [email protected].
  • 7. Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. [email protected].
  • 8. Al-Jeraisy Chair for DNA Research, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. [email protected].
  • 9. Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia. [email protected].
  • 10. Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia. [email protected].
PMID: 25961160 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.

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