Novel 1-(2-aryl-2-adamantyl)piperazine derivatives with antiproliferative activity

  • Eur J Med Chem. 2015 Mar 26:93:281-90. doi: 10.1016/j.ejmech.2015.02.021.
Christos Fytas  1 ,  Grigoris Zoidis  1 ,  Andrew Tsotinis  1 ,  George Fytas  2 ,  Mohsin A Khan  3 ,  Samar Akhtar  3 ,  Khondaker M Rahman  3 ,  David E Thurston  3
Affiliations
  • 1. School of Health Sciences, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, GR-15784 Athens, Greece.
  • 2. School of Health Sciences, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, University of Athens, Panepistimioupoli-Zografou, GR-15784 Athens, Greece. Electronic address: [email protected].
  • 3. Institute of Pharmaceutical Sciences, King's College London, Britannia House, 7 Trinity Street, London SE1 1DB, UK.
PMID: 25703296 DOI: 10.1016/j.ejmech.2015.02.021
Abstract

Novel 1-(2-aryl-2-adamantyl)piperazine derivatives have been synthesized and evaluated in vitro for their antitumor properties against HeLa cervical carcinoma, MDA MB 231 breast Cancer, MIA PaCa2 pancreatic Cancer, and NCI H1975 non-small cell lung Cancer. The parent piperazine 6 was found to exhibit a reasonable activity toward the HeLa and MDA MB 231 tumor cell lines (IC50= 9.2 and 8.4 μΜ, respectively). Concurrent benzene ring C4-fluorination and piperidine acetylation of the piperazino NH of compound 6 resulted in the most active compound 13 of the series in both of the above cell lines (IC50=8.4 and 6.8 μΜ, respectively). Noticeably, compounds 6 and 13 exhibited a significantly low cytotoxicity level over the normal human cells HUVEC (Human Umbilical Vein Endothelial Cells) and NHDF (Normal Human Dermal Fibroblasts).

Keywords
1-(2-aryl-2-adamantyl)piperazines; In vitro antiproliferative activity; N-Boc deprotection; NMR; σ1, σ2-Binding affinity.