A new series of spiro-cyclic sigma ligands were prepared and studied. Most were found to have a high affinity and selectivity for σ1R; compounds 7b, 15b and 16a were shown to be σ1R agonists, while 16b was proven to be the only σ1R antagonist. Only 16a (BS148) exhibited σ2R selectivity and was able to inhibit the growth of metastatic malignant melanoma cell lines, whilst not affecting normal human melanocytes. BS148’s anti-proliferative activity suggests a σ2R agonist profile. Further, preliminary investigations indicate that, at least a part, the mechanism of metastatic malignant melanoma cell death induced by BS148 is due to apoptosis.

Structure-Activity Relationship within a new series of σ1 and σ2 receptor ligands: identification of a novel σ2R agonist (BS148) with selective toxicity against metastatic melanoma / Franchini, Silvia; Sorbi, Claudia; Battisti, Umberto Maria; Tait, Annalisa; Bencheva, Leda Ivanova; Cichero, Elena; Fossa, Paola; Cilia, Antonio; Prezzavento, Orazio; Ronsisvalle, Simone; Aricò, Giuseppina; Benassi, Luisa; Vaschieri, Cristina; Azzoni, Paola; Magnoni, Cristina; Brasili, Livio. - In: CHEMMEDCHEM. - ISSN 1860-7179. - 12:22(2017), pp. 1893-1905. [10.1002/cmdc.201700427]

Structure-Activity Relationship within a new series of σ1 and σ2 receptor ligands: identification of a novel σ2R agonist (BS148) with selective toxicity against metastatic melanoma

Franchini, Silvia;Sorbi, Claudia;Battisti, Umberto Maria;Tait, Annalisa;Benassi, Luisa;Vaschieri, Cristina;Azzoni, Paola;Magnoni, Cristina;Brasili, Livio
2017

Abstract

A new series of spiro-cyclic sigma ligands were prepared and studied. Most were found to have a high affinity and selectivity for σ1R; compounds 7b, 15b and 16a were shown to be σ1R agonists, while 16b was proven to be the only σ1R antagonist. Only 16a (BS148) exhibited σ2R selectivity and was able to inhibit the growth of metastatic malignant melanoma cell lines, whilst not affecting normal human melanocytes. BS148’s anti-proliferative activity suggests a σ2R agonist profile. Further, preliminary investigations indicate that, at least a part, the mechanism of metastatic malignant melanoma cell death induced by BS148 is due to apoptosis.
30-ott-2017
12
22
1893
1905
Structure-Activity Relationship within a new series of σ1 and σ2 receptor ligands: identification of a novel σ2R agonist (BS148) with selective toxicity against metastatic melanoma / Franchini, Silvia; Sorbi, Claudia; Battisti, Umberto Maria; Tait, Annalisa; Bencheva, Leda Ivanova; Cichero, Elena; Fossa, Paola; Cilia, Antonio; Prezzavento, Orazio; Ronsisvalle, Simone; Aricò, Giuseppina; Benassi, Luisa; Vaschieri, Cristina; Azzoni, Paola; Magnoni, Cristina; Brasili, Livio. - In: CHEMMEDCHEM. - ISSN 1860-7179. - 12:22(2017), pp. 1893-1905. [10.1002/cmdc.201700427]
Franchini, Silvia; Sorbi, Claudia; Battisti, Umberto Maria; Tait, Annalisa; Bencheva, Leda Ivanova; Cichero, Elena; Fossa, Paola; Cilia, Antonio; Prezzavento, Orazio; Ronsisvalle, Simone; Aricò, Giuseppina; Benassi, Luisa; Vaschieri, Cristina; Azzoni, Paola; Magnoni, Cristina; Brasili, Livio
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1153749
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