{rfName}
Sy

Indexed in

License and Use

Icono OpenAccess

Citations

13

Altmetrics

Analysis of institutional authors

Barbaraci, CarlaAuthor

Share

August 4, 2024
Publications
>
Article
Sí

Synthesis, Computational Insights, and Evaluation of Novel Sigma Receptors Ligands.

Publicated to: Acs Chemical Neuroscience. 14 (10): 1845-1858 - 2023-05-17 14(10), DOI: 10.1021/acschemneuro.3c00074

Authors:

Dichiara M; Ambrosio FA; Barbaraci C; González-Cano R; Costa G; Parenti C; Marrazzo A; Pasquinucci L; Cobos EJ; Alcaro S; Amata E
[+]

Affiliations

Departamento de Farmacología e Instituto de Neurociencias, Facultad de Medicina, Universitad de Granada e Instituto de Investigación Biosanitaria de Granada ibs.GRANADA, Avenida de la Investigación 11, 18016 Granada, Spain. - Author
Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi "Magna Græcia" di Catanzaro, Campus "S. Venuta", Viale Europa, 88100 Catanzaro, Italy. - Author
Dipartimento di Scienze del Farmaco e della Salute, Università degli Studi di Catania, Viale Andrea Doria 6, 95125 Catania, Italy. - Author
Dipartimento di Scienze della Salute, Università "Magna Græcia" di Catanzaro, Campus "S. Venuta", 88100 Catanzaro, Italy. - Author
See more

Abstract

The development of diazabicyclo[4.3.0]nonane and 2,7-diazaspiro[3.5]nonane derivatives as sigma receptors (SRs) ligands is reported. The compounds were evaluated in S1R and S2R binding assays, and modeling studies were carried out to analyze the binding mode. The most notable compounds, 4b (AD186, KiS1R = 2.7 nM, KiS2R = 27 nM), 5b (AB21, KiS1R = 13 nM, KiS2R = 102 nM), and 8f (AB10, KiS1R = 10 nM, KiS2R = 165 nM), have been screened for analgesic effects in vivo, and their functional profile was determined through in vivo and in vitro models. Compounds 5b and 8f reached the maximum antiallodynic effect at 20 mg/kg. The selective S1R agonist PRE-084 completely reversed their action, indicating that the effects are entirely dependent on the S1R antagonism. Conversely, compound 4b sharing the 2,7-diazaspiro[3.5]nonane core as 5b was completely devoid of antiallodynic effect. Interestingly, compound 4b fully reversed the antiallodynic effect of BD-1063, indicating that 4b induces an S1R agonistic in vivo effect. The functional profiles were confirmed by the phenytoin assay. Our study might establish the importance of 2,7-diazaspiro[3.5]nonane core for the development of S1R compounds with specific agonist or antagonist profile and the role of the diazabicyclo[4.3.0]nonane in the development of novel SR ligands.
[+]

Keywords

AlkanesDrug discoveryLigandsMechanical hypersensitivityMolecular modelingNonaneReceptors, sigmaS1r agonistS1r antagonistSigma receptorsSr ligands

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Acs Chemical Neuroscience due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2023, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Medicine (Miscellaneous).

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2026-01-20:

  • Europe PMC: 6
[+]

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-01-20:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 11 (PlumX).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
[+]

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Granada; Italy.

[+]