Novel derivatives of 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) with improved fluorescent and σ receptors binding properties

J Med Chem. 2014 Apr 24;57(8):3314-23. doi: 10.1021/jm401874n. Epub 2014 Apr 14.


Despite the promising potentials of σ2 receptors in cancer therapy and diagnosis, there are still ambiguities related to the nature and physiological role of the σ2 protein. With the aim of providing potent and reliable tools to be used in σ2 receptor research, we developed a novel series of fluorescent σ2 ligands on the basis of our previous work, where high-affinity σ2 ligand 1-cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-n-propyl]piperazine (1, PB28) was used as the pharmacophore. Compared to the previous compounds, these novel ligands displayed improved fluorescence and σ2 binding properties, were σ2-specifically taken up by breast tumor cells, and were successfully employed in confocal microscopy. Compound 14, which was the best compromise between pharmacological and fluorescent properties, was successfully employed in flow cytometry, demonstrating its potential to be used as a tool in nonradioactive binding assays for studying the affinity of putative σ2 receptor ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Flow Cytometry
  • Fluorescence
  • Guinea Pigs
  • Humans
  • Ligands
  • MCF-7 Cells
  • Male
  • Piperazines / chemical synthesis*
  • Piperazines / metabolism
  • Rats
  • Receptors, sigma / metabolism*


  • Ligands
  • PB28 compound
  • Piperazines
  • Receptors, sigma