2-Phenyl-3-(Phenylselanyl)Benzofuran As a Promising Antidepressant Candidate: Mechanistic Insights Into Nitrergic Modulation and Subchronic Efficacy and Safety Profiling.

Overview

Authors: Taís da Silva Teixeira Rech¹, Ediandra Tissot Castro¹, Mariana Parron Paim¹, Dianer Nornberg Strelow¹, José Sebastião Santos Neto^2,3, Gustavo Bierhals Blödorn³, Diego Alves³, Suzan Gonçalves Rosa⁴, César Augusto Brüning¹, Cristiani Folharini Bortolatto¹

ORCID iDs: Taís da Silva Teixeira Rech, Ediandra Tissot Castro, Mariana Parron Paim, Dianer Nornberg Strelow, José Sebastião Santos Neto, Gustavo Bierhals Blödorn, Diego Alves, Suzan Gonçalves Rosa, César Augusto Brüning, Cristiani Folharini Bortolatto

Institutions: Universidade Federal de Pelotas (Brazil); Universidade Federal de Goiás (Brazil); Universidade Federal do Pampa (Brazil)

Journal: Molecular neurobiology, volume 63, issue 1, article 771

Dates: received 31 January 2026; accepted 8 July 2026; published online 16 July 2026; in print 2026

Type: Research article · Language: English

License: CC BY

Identifiers: DOI 10.1007/s12035-026-06058-6 · PMID 42461353 · PMCID PMC13375843 · OpenAlex W7168890894

Open access: hybrid, a free copy (OpenAlex)

Status: data only

Categories: mouse (organism), depression (population)

Methods: Statistics, Connectivity

Keywords: SeBZF1, Antidepressant, NO-cGMP, Mice, Selenium, Tail suspension test

MeSH: Antidepressive Agents*, Benzofurans*, Nitric Oxide*, Animals, Cyclic GMP, Hindlimb Suspension, Male, Mice, Molecular Docking Simulation (* major topic)

Topic: Organoselenium and organotellurium chemistry (Toxicology, Pharmacology, Toxicology and Pharmaceutics), according to OpenAlex

Funding: Coordination for the Improvement of Higher Education Personnel (438384/2018–0, 420386/2018–1); State of Rio Grande do Sul Research Support Foundation (21/2551-0000614-5–0, 21/2551-0000728-1); Universidade Federal De Pelotas

Citations: not cited yet (Europe PMC); 81 references in the paper

Abstract

The compound 2-phenyl-3-(phenylselanyl)benzofuran (SeBZF1), a selenium-containing molecule based on a benzofuran scaffold, has shown antidepressant-like effects. This study investigated the involvement of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway, the efficacy of subchronic treatment in male Swiss mice, and computational analyses. Acute SeBZF1 administration (50 mg/kg, i.g.) showed antidepressant-like effects in the tail suspension test (TST). These effects were reversed by pretreatment with L-arginine (a NO precursor, 750 mg/kg, intraperitoneal, i.p.) or sildenafil (a phosphodiesterase-5 inhibitor, 5 mg/kg, i.p.), suggesting NO-cGMP pathway involvement. A subeffective dose of SeBZF1 (1 mg/kg, i.g.) elicited synergistic antidepressant-like effects when combined with N(ω)-nitro-L-arginine methyl ester (L-NAME, a nitric oxide synthase (NOS) inhibitor, 10 mg/kg, i.p.) or 7-nitroindazole (a specific neuronal NOS inhibitor, 30 mg/kg, i.p.). Furthermore, methylene blue (an inhibitor of NOS and soluble guanylate cyclase (sGC), 10 mg/kg, i.p.) and 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, a sGC inhibitor, 30 pmol/site, intracerebroventricular), both soluble guanylate cyclase (sGC) inhibitors, enhanced the subeffective SeBZF1 dose. Subchronic SeBZF1 treatment (1 mg/kg, i.g., for 35 days) significantly produced antidepressant-like action without causing weight loss or organ damage. Biochemical analysis revealed reduced nitrate/nitrite levels in the prefrontal cortex and hippocampus, indicating modulation of NO signaling. Molecular docking suggested interactions between SeBZF1 and NOS isoforms, while pharmacokinetic analysis suggested brain penetration and absence of overt toxicity. The present study concludes that SeBZF1 exhibits antidepressant-like effects through the NO–cGMP pathway, is effective at low subchronic doses, and displays favorable pharmacokinetic and safety profiles, supporting its potential as a novel antidepressant candidate.

Supplementary Information: The online version contains supplementary material available at 10.1007/s12035-026-06058-6.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

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Data

Datasets cited

pdb.org, at pdb.org; found in the text, “Molecular Docking”

Data Availability

The datasets generated and/or analyzed during the current study are available from the corresponding author upon request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

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Version 2, 28 September 2026

Publisher: n/a → Springer Science+Business Media

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 10 authors, 6 keywords, 9 MeSH terms, 3 funders, 80 references.

Cite

This paper

Rech, T. d. S. T., Castro, E. T., Paim, M. P., Strelow, D. N., Neto, J. S. S., Blödorn, G. B., Alves, D., Rosa, S. G., Brüning, C. A., & Bortolatto, C. F. (2026). 2-Phenyl-3-(Phenylselanyl)Benzofuran As a Promising Antidepressant Candidate: Mechanistic Insights Into Nitrergic Modulation and Subchronic Efficacy and Safety Profiling. Molecular neurobiology, 63(1), 771. https://doi.org/10.1007/s12035-026-06058-6

BibTeX

@article{rech20262, author = {Rech, Taís da Silva Teixeira and Castro, Ediandra Tissot and Paim, Mariana Parron and Strelow, Dianer Nornberg and Neto, José Sebastião Santos and Blödorn, Gustavo Bierhals and Alves, Diego and Rosa, Suzan Gonçalves and Brüning, César Augusto and Bortolatto, Cristiani Folharini}, title = {{2-Phenyl-3-(Phenylselanyl)Benzofuran As a Promising Antidepressant Candidate: Mechanistic Insights Into Nitrergic Modulation and Subchronic Efficacy and Safety Profiling}}, journal = {Molecular neurobiology}, year = {2026}, month = jul, volume = {63}, number = {1}, pages = {771}, publisher = {Springer Science+Business Media}, issn = {0893-7648}, doi = {10.1007/s12035-026-06058-6}, url = {https://doi.org/10.1007/s12035-026-06058-6}, pmid = {42461353}, pmcid = {PMC13375843} }

RIS

TY - JOUR AU - Rech, Taís da Silva Teixeira AU - Castro, Ediandra Tissot AU - Paim, Mariana Parron AU - Strelow, Dianer Nornberg AU - Neto, José Sebastião Santos AU - Blödorn, Gustavo Bierhals AU - Alves, Diego AU - Rosa, Suzan Gonçalves AU - Brüning, César Augusto AU - Bortolatto, Cristiani Folharini TI - 2-Phenyl-3-(Phenylselanyl)Benzofuran As a Promising Antidepressant Candidate: Mechanistic Insights Into Nitrergic Modulation and Subchronic Efficacy and Safety Profiling T2 - Molecular neurobiology J2 - Mol Neurobiol PY - 2026 DA - 2026/07/16 VL - 63 IS - 1 SP - 771 SN - 0893-7648 PB - Springer Science+Business Media DO - 10.1007/s12035-026-06058-6 UR - https://doi.org/10.1007/s12035-026-06058-6 LA - en ER -

CSL-JSON

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