Chalcogen dihydrobenzofuran compounds as potential neuroprotective agents: An in vitro and in silico biological investigation
- PMID: 39880296
- DOI: 10.1016/j.biochi.2025.01.006
Chalcogen dihydrobenzofuran compounds as potential neuroprotective agents: An in vitro and in silico biological investigation
Abstract
Oxidative stress arises from an imbalance between reactive species (RS) production and the antioxidant defense, increasing the brain susceptibility to neurodegenerative and psychiatric diseases. Besides, changes in the expression or activity of neurotransmitter metabolism enzymes, such as monoamine oxidases (MAO), are also associated with mental disorders, including depression. Considering this, antioxidant and MAO-A activity inhibitory potential of six 2,3-chalcogenodihydrobenzofurans (2,3-DHBF) was investigated through in vitro and in silico tests. Compounds 1 to 5 incorporate sulfur (S) as chalcogen, whereas compound 6 integrates tellurium (Te). A screening (compounds 1-6) of cerebral MAO-A activity showed inhibitory activity for the compounds 2, 4, 5, and 6. Among sulfur compounds, compound 2 demonstrated superior scores in docking studies, yielding a value of - 9.9 kcal/mol. Selected for concentration-response curves, compounds 2 (with S) and 6 (with Te) inhibited MAO-A at concentrations equal to or higher than 25 μM. In a redox screening test, only compound 6 showed antioxidant effects. Concentration-response curves indicated that compound 6 reduced lipid peroxidation and protein carbonylation levels in mouse brain tissue (≥0.5 μM), as well as reduced RS levels (≥1 μM). Furthermore, the compound 6 (≥5 μM) was effective in reducing the ferric ion (FRAP). In radical scavenging tests such as 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), compound 6 showed significant results in concentrations from 50 μM and mimicked the enzyme glutathione S-transferase (GST) at 100 μM. In summary, this study demonstrated the cerebral antioxidant and/or MAO-A inhibition properties of 2,3-DHBF, presenting potential as neuroprotective candidates.
Keywords: 2,3-Chalcogenodihydrobenzofurans; Antioxidant; Brain; Monoamine oxidase-A; Sulfur; Tellurium.
Copyright © 2025 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.
Conflict of interest statement
Declaration of interests The authors declare that there is no conflict of interest associated with this publication. Financial support was exclusively provided by government institutions that do not qualify as potential conflicts of interest, as described below: Cristiani Folharini Bortolatto reports financial support was provided by Coordination of Higher Education Personnel Improvement (CAPES). Cristiani Folharini Bortolatto reports financial support was provided by Foundation for Research Support of Rio Grande do Sul State (FAPERGS). Tacia Katiane Hall reports financial support was provided by Coordination of Higher Education Personnel Improvement (CAPES). Cesar Augusto Bruning reports financial support was provided by Foundation for Research Support of Rio Grande do Sul State (FAPERGS). Vanessa Nascimento reports financial support was provided by Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State. Vanessa Nascimento reports financial support was provided by National Research Council of Science and Technology. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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