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Silodosin as a Novel Inhibitor of Acetylcholinesterase, Butyrylcholinesterase, and BETA-Secretase 1: In Vitro and In Silico Studies
Deyse Brito Barbosa, Lucas Matheus Gonçalves de Oliveira, Géssica Oliveira Mendes, David Bacelar Costa, Tiago Alves de Oliveira, Michel Pires da Silva, Laila Cristina Moreira Damázio, Eduardo Habib Bechelane Maia et al.. ACS Omega, 2025-10-09
Topic: Brain proteins, microglia and lab models
Alzheimer's Disease (AD) is a progressive neurodegenerative disorder and the leading cause of cognitive decline in older adults. Several biomarkers of AD have been identified, but its pathogenesis has not yet been completely elucidated. One of the most relevant hypotheses proposed to explain the cognitive impairment caused by this disease is the cholinergic hypothesis, which postulates that loss of cholinergic neurons is one of its causes and that the subsequent reduction of acetylcholine levels in the synaptic cleft can be compensated through the inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Another well-known hypothesis is the amyloid-beta hypothesis, which explains the disease as being caused by the formation and accumulation of amyloid plaques in a cascade of enzymatic events starting with the cleavage of an amyloid precursor protein (APP) by beta-secretase 1 (BACE-1). Previous studies have shown that silodosin has the structural requirements for the inhibition of those three enzymes (AChE, BuChE, and BACE-1), which suggests that it can be useful as a multitarget candidate to treat Alzheimer patients. This study aims to assess the effect of silodosin on cellular viability, measure the inhibitory activity against AChE, BuChE, and BACE-1, and evaluate the molecular behavior of all three inhibitor-enzyme systems by molecular dynamics (MD) simulations. Cell viability assays through the MTT method showed that silodosin concentrations of less than 10 μM are safe to be used. Enzymatic assays revealed AChE inhibitory activity at high micromolar levels (IC50 >500.0 μM) but inhibited BuChE at low micromolar levels (IC50 = 3.02 ± 0.05 μM). BACE-1 inhibition assays have shown significant reduction at three micromolar. MD simulations demonstrated that silodosin promotes late stabilization of the AChE complex, but the simulations involving BuChE and BACE-1 revealed that the compound promotes system stabilization at early stages and has the structural requirements to inhibition.
Key findings
- Previous studies have shown that silodosin has the structural requirements for the inhibition of those three enzymes (AChE, BuChE, and BACE-1), which suggests that it can be useful as a multitarget candidate to treat Alzheimer patients.
- Cell viability assays through the MTT method showed that silodosin concentrations of less than 10 μM are safe to be used.
- Enzymatic assays revealed AChE inhibitory activity at high micromolar levels (IC50 >500.0 μM) but inhibited BuChE at low micromolar levels (IC50 = 3.02 ± 0.05 μM).
- BACE-1 inhibition assays have shown significant reduction at three micromolar.
- MD simulations demonstrated that silodosin promotes late stabilization of the AChE complex, but the simulations involving BuChE and BACE-1 revealed that the compound promotes system stabilization at early stages and has the structural requirements to inhibition.
Why it matters
In laboratory experiments, silodosin inhibited butyrylcholinesterase at low micromolar levels but inhibited acetylcholinesterase only at high micromolar levels, and cell viability assays showed concentrations under 10 micromolar were safe. This is an in vitro and in silico study, so it does not show that silodosin treats Alzheimer's disease in people.
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Study details
- Evidence strengthLow
How this study scored 37/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (ACS Omega) |
| Journal's citation record | 2 / 4 | ACS Omega: journal h-index 178 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Laboratory or animal study (title names “in vitro”) — scores zero |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 6 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 3.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 6 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 1 / 4 | Last-listed author Franco Henrique Andrade Leite: h-index 17 (OpenAlex, whole career) |
| Institution's track record | 0 / 3 | Universidade Federal da Bahia: institution h-index 323 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41141721) |
| Free to read | 2 / 2 | Free to read |
| Total | 37 / 100 | — |
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Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Barbosa, D. B., de Oliveira, L. M. G., Mendes, G. O., Costa, D. B., de Oliveira, T. A., da Silva, M. P., et al. (2025). Silodosin as a Novel Inhibitor of Acetylcholinesterase, Butyrylcholinesterase, and BETA-Secretase 1: In Vitro and In Silico Studies. ACS Omega. https://doi.org/10.1021/acsomega.5c07084
Vancouver
Barbosa DB, de Oliveira LMG, Mendes GO, Costa DB, de Oliveira TA, da Silva MP, et al. Silodosin as a Novel Inhibitor of Acetylcholinesterase, Butyrylcholinesterase, and BETA-Secretase 1: In Vitro and In Silico Studies. ACS Omega. 2025. doi:10.1021/acsomega.5c07084. PMID: 41141721.
BibTeX
@article{barbosa2025-41141721,
author = {Barbosa, Deyse Brito and de Oliveira, Lucas Matheus Gonçalves and Mendes, Géssica Oliveira and Costa, David Bacelar and de Oliveira, Tiago Alves and da Silva, Michel Pires and Damázio, Laila Cristina Moreira and Maia, Eduardo Habib Bechelane and others},
title = {{Silodosin as a Novel Inhibitor of Acetylcholinesterase, Butyrylcholinesterase, and BETA-Secretase 1: In Vitro and In Silico Studies}},
journal = {ACS Omega},
year = {2025},
doi = {10.1021/acsomega.5c07084},
pmid = {41141721},
url = {https://doi.org/10.1021/acsomega.5c07084}
}
Studies this one cites
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