Novel Derivatives of 1-Cyclohexyl-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine (PB28) with Improved Fluorescent and a Receptors Binding Properties

Despite the promising potentials of sigma(2) receptors in cancer therapy and diagnosis, there are still ambiguities related to the nature and physiological role of the a, protein. With the aim of providing potent and reliable tools to be used in sigma(2) receptor research, we developed a novel series of fluorescent sigma(2) ligands on the basis of our previous work, where high-affinity sigma(2) 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 a, binding properties, were sigma(2)-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 sigma(2) receptor ligands.