2. Academic Validation
  3. 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

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

  • ChemMedChem. 2017 Nov 22;12(22):1893-1905. doi: 10.1002/cmdc.201700427.
Silvia Franchini 1,  Claudia Sorbi 1,  Umberto Maria Battisti 1,  Annalisa Tait 1,  Leda Ivanova Bencheva 1,  Elena Cichero 2,  Paola Fossa 2,  Antonio Cilia 3,  Orazio Prezzavento 4,  Simone Ronsisvalle 4,  Giuseppina Aricò 4,  Luisa Benassi 5,  Cristina Vaschieri 5,  Paola Azzoni 5,  Cristina Magnoni 5,  Livio Brasili 1
Affiliations

Affiliations

  • 1 Dipartimento di Scienze della Vita, Università degli Studi di Modena e Reggio Emilia, Via Campi 103, 41125, Modena, Italy.
  • 2 Dipartimento di Farmacia, Università degli Studi di Genova, Viale Benedetto XV 3, 16132, Genova, Italy.
  • 3 Divisione Ricerca e Sviluppo, Recordati S.p.A., Via Civitali 1, 20148, Milano, Italy.
  • 4 Dipartimento di Scienze del Farmaco, Università degli Studi di Catania, Viale Andrea Doria 6, 95125, Catania, Italy.
  • 5 Dipartimento Chirurgico, Medico, Odontoiatrico e di Scienze Morfologiche con interesse Trapiantologico, Oncologico e di Medicina Rigenerativa, Università degli Studi di Modena e Reggio Emilia, via del Pozzo 71, 41124, Modena, Italy.
PMID: 28940806 DOI: 10.1002/cmdc.201700427
Abstract

A new series of spirocyclic σ receptor (σR) ligands were prepared and studied. Most were found to have a high affinity and selectivity for σ1 R; three compounds were shown to be σ1 R agonists, while another proved to be the only σ1 R antagonist. Only one of the σ1 R agonists (BS148) also exhibited σ2 R 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 σ2 R 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.

Keywords

SK-MEL-2 cells; analgesia; antiproliferative activity; melanoma; sigma receptors.

Figures
Products