New Tacrine Dimers Alleviate the Intracellular Amyloid-β-induced Cognitive Disturbance and Oxidative Stress in Mice
This study aimed to investigate <italic>in vivo</italic> and <italic>ex-vivo</italic> the effects of tacrine dimers (TD1, TD2, TD3 and TD4) in mice with Alzheimer's disease (AD) induced by amyloid peptide (A<italic>β</italic>42) and, respectively, evaluated in behavioral tests of cognition, oxidative stress and neuroinflammation. All dimers reduced the cognitive deficit caused by A<italic>β</italic>42, oxidative stress and neuroinflammation, especially the compound TD4. By ADMET analysis (SwissADME and pkCSM 2.10 platforms), TD4 exhibited favorable pharmacokinetic properties with the control drug. The results suggest a therapeutic potential for AD for these compounds, given their distinct cognitive and neuroprotective effects in AD models induced by A<italic>β</italic>42.
Authors
- Sumbal Saba (ORCID: https://orcid.org/0000-0002-6134-7249)
- Yuri de Freitas Rego (ORCID: https://orcid.org/0000-0003-4660-6852)
- Luísa Mota da Silva (ORCID: https://orcid.org/0000-0001-5329-7301)
- Jamal Rafique (ORCID: https://orcid.org/0000-0002-2336-040X)
- Márcia María de Souza (ORCID: https://orcid.org/0000-0002-6297-9635)
- Clara Herrera‐Arozamena (ORCID: https://orcid.org/0000-0002-5894-128X)
- Thiago Henrique Doring (ORCID: https://orcid.org/0000-0002-3611-9105)
- Marı́a Isabel Rodrı́guez-Franco (ORCID: https://orcid.org/0000-0002-6500-792X)
- Aldo Sena de Oliveira (ORCID: https://orcid.org/0000-0001-7760-4484)
- Ângelo de Fátima (ORCID: https://orcid.org/0000-0003-2344-5590)
- Ana Elisa Gonçalves (ORCID: https://orcid.org/0000-0002-5148-7184)
- Maria Lı́gia Rodrigues Macedo (ORCID: https://orcid.org/0000-0001-6969-6307)
- LUCAS AUGUSTO ARAUJO (ORCID: https://orcid.org/0009-0001-7902-6136)
- OTTO SPIGARIOL
Institutions
- Universidade Federal de Minas Gerais (BR)
- Universidade Federal de Mato Grosso do Sul (BR)
- Universidade Federal de Santa Catarina (BR)
- Instituto de Química Médica (ES)
- Universidade do Vale do Itajaí (BR)
- Universidade Federal de Goiás (BR)
Publication Details
- Journal
- Anais da Academia Brasileira de Ciências
- Published
- 2025-01-01
- DOI
- https://doi.org/10.1590/0001-3765202520241163
- Primary Topic
- Cholinesterase and Neurodegenerative Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Ministerio de Ciencia, Innovación y Universidades
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação de Amparo à Pesquisa do Estado de Minas Gerais
- Fundação de Amparo à Pesquisa do Estado de Goiás
- Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina