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

Fabio Del Bello; Maria Vittoria Micioni Di Bonaventura; Alessandro Bonifazi; Bernhard Wünsch; Dirk Schepmann; Jolynn B. Giancola; Emanuela Micioni Di Bonaventura; Giulio Vistoli; Gianfabio Giorgioni; Wilma Quaglia; Alessandro Piergentili; Carlo Cifani

doi:10.1021/acschemneuro.9b00261

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

Fabio Del Bello, Maria Vittoria Micioni Di Bonaventura, Alessandro Bonifazi, Bernhard Wünsch, Dirk Schepmann, Jolynn B. Giancola, Emanuela Micioni Di Bonaventura, Giulio Vistoli, Gianfabio Giorgioni, Wilma Quaglia, Alessandro Piergentili, Carlo Cifani

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	3391-3397
Number of pages	7
Journal	ACS chemical neuroscience
Volume	10
Issue number	8
DOIs	https://doi.org/10.1021/acschemneuro.9b00261
State	Published - Aug 21 2019
Externally published	Yes

Keywords

Selective σ antagonists
binge eating episode
chirality
docking studies
palatable food

ASJC Scopus subject areas

Biochemistry
Physiology
Cognitive Neuroscience
Cell Biology

Access to Document

10.1021/acschemneuro.9b00261

Cite this

Del Bello, F., Micioni Di Bonaventura, M. V., Bonifazi, A., Wünsch, B., Schepmann, D., Giancola, J. B., Micioni Di Bonaventura, E., Vistoli, G., Giorgioni, G., Quaglia, W., Piergentili, A., & Cifani, C. (2019). 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. ACS chemical neuroscience, 10(8), 3391-3397. https://doi.org/10.1021/acschemneuro.9b00261

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 et al.
In: ACS chemical neuroscience, Vol. 10, No. 8, 21.08.2019, p. 3391-3397.

Research output: Contribution to journal › Article › peer-review

Del Bello, F, Micioni Di Bonaventura, MV, Bonifazi, A, Wünsch, B, Schepmann, D, Giancola, JB, Micioni Di Bonaventura, E, Vistoli, G, Giorgioni, G, Quaglia, W, Piergentili, A & Cifani, C 2019, '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', ACS chemical neuroscience, vol. 10, no. 8, pp. 3391-3397. https://doi.org/10.1021/acschemneuro.9b00261

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abstract = "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.",

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AU - Vistoli, Giulio

AU - Giorgioni, Gianfabio

AU - Quaglia, Wilma

AU - Piergentili, Alessandro

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N2 - 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.

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