A new series of spirocyclic Ï receptor (ÏR) ligands were prepared and studied. Most were found to have a high affinity and selectivity for Ï1R; three compounds were shown to be Ï1R agonists, while another proved to be the only Ï1R antagonist. Only one of the Ï1R agonists (BS148) also exhibited Ï2R selectivity and was able to inhibit the growth of metastatic malignant melanoma cell lines without affecting normal human melanocytes. The antiproliferative activity of this compound suggested an Ï2R agonist profile. Further, preliminary investigations indicated that the mechanism of metastatic malignant melanoma cell death induced by BS148 is due, at least in part, to apoptosis.
|Titolo:||Structure-Activity Relationships within a Series of σ1 and σ2 Receptor Ligands: Identification of a σ2 Receptor Agonist (BS148) with Selective Toxicity against Metastatic Melanoma|
|Data di pubblicazione:||2017|
|Appare nelle tipologie:||1.1 Articolo in rivista|