1204401-49-9Relevant articles and documents
Investigation of the Role of Chirality in the Interaction with σ Receptors and Effect on Binge Eating Episode of a Potent σ1 Antagonist Analogue of Spipethiane
Del Bello, Fabio,Micioni Di Bonaventura, Maria Vittoria,Bonifazi, Alessandro,Wünsch, Bernhard,Schepmann, Dirk,Giancola, Jolynn B.,Di Bonaventura, Emanuela Micioni,Vistoli, Giulio,Giorgioni, Gianfabio,Quaglia, Wilma,Piergentili, Alessandro,Cifani, Carlo
, p. 3391 - 3397 (2019)
The enantiomers of the potent σ1 receptor antagonist (±)-1 were synthesized and evaluated for their affinity at σ1, σ2 receptors and dopamine transporter (DAT). Analogously to (±)-1, both of the enantiomers showed very high affinity for the σ1 receptor and unprecedented selectivity over both the σ2 receptor and DAT. The lack of enantioselectivity between (+)-1 and (-)-1 indicated that the center of chirality in the 2-position of the benzothiochromane nucleus does not play a crucial role in the interaction with any of the studied targets. Docking studies confirmed that the configuration of the enantiomers has only marginal effects on the molecular interactions with the σ1 receptor. In in vivo studies in a female rat model of binge eating, (±)-1 dose-dependently decreased the binge eating episode elicited by a history of intermittent food restriction and stress, confirming and strengthening the important role played by the σ1 receptor in bingeing-related eating disorders.
Novel highly potent and selective σ1 receptor antagonists related to spipethiane
Piergentili, Alessandro,Amantini, Consuelo,Del Bello, Fabio,Giannella, Mario,Mattioli, Laura,Palmery, Maura,Perfumi, Marina,Pigini, Maria,Santoni, Giorgio,Tucci, Paolo,Zotti, Margherita,Quaglia, Wilma
experimental part, p. 1261 - 1269 (2010/07/18)
Conservative chemical modifications of the core structure of the lead spipethiane (1) afforded novel potent σ1 ligands. σ1 affinity and σ1/σ2 selectivity proved to be favored by the introduction of polar functions (oxygen atom or carbonyl group) in position 3 or 4 (4-6) or by the elongation of the distance between the two hydrophobic portions of the molecule with the simultaneous presence of a carbonyl group in position 4 (8 and 9). The observed cytostatic effect against the human breast cancer cell line MCF-7/ADR, highly expressing σ1 receptors, and not against MCF-7, as well as the enhancement of morphine analgesia highlighted the σ1 antagonist profile of this series of compounds. In particular, due to its high σ1 affinity (pKi = 10.28) and σ1/ σ2 selectivity ratio (29510), compound 9 might be a novel valuable tool for σ receptor characterization and a suitable template for the rational design of potential therapeutically useful σ1 antagonists. 2010 American Chemical Society.
