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. Epub 2015 Feb 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / chemistry*
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Design
  • HeLa Cells
  • Humans
  • Piperazine
  • Piperazines / chemistry*
  • Piperazines / metabolism
  • Piperazines / pharmacology*
  • Receptors, sigma / metabolism

Substances

  • Antineoplastic Agents
  • Piperazines
  • Receptors, sigma
  • Piperazine
  • Adamantane