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Multitarget Effect of 2-(4-(Methylthio)phenyl)-3-(3-(piperidin-1-yl)propyl)thiazolidin-4-one in a Scopolamine-Induced Amnesic Rat Model

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Abstract

Cholinergic system dysfunction, oxidative damage, and alterations in ion pump activity have been associated with memory loss and cognitive deficits in Alzheimer’s disease. 1,3-thiazolidin-4-ones have emerged as a class of compounds with potential therapeutic effects due to their potent anticholinesterase activity. Accordingly, this study investigated the effect of the 2-(4-(methylthio)phenyl)-3-(3-(piperidin-1-yl)propyl)thiazolidin-4-one (DS12) compound on memory, cholinergic and oxidative stress parameters, ion pump activity, and serum biochemical markers in a scopolamine-induced memory deficit model. Male Wistar rats were divided into four groups: I-Control; II-Scopolamine; III-DS12 (5 mg/kg) + scopolamine; and IV-DS12 (10 mg/kg) + scopolamine. The animals from groups III and IV received DS12 diluted in canola oil and administered for 7 days by gavage. On the last day of treatment, scopolamine (1 mg/kg) was administered intraperitoneally (i.p.) 30 min after training in an inhibitory avoidance apparatus. Twenty-four hours after scopolamine administration, the animals were subjected to an inhibitory avoidance test and were thereafter euthanized. Scopolamine induced memory deficits, increased acetylcholinesterase activity and oxidative damage, and decreased Na+/K+-ATPase activity in cerebral cortex and hippocampus. Pretreatment with DS12 prevented these brain alterations. Scopolamine also induced an increase in acetylcholinesterase activity in lymphocytes and whereas butyrylcholinesterase in serum and treatment with DS12 prevented these changes. In animals treated with DS12, no changes were observed in renal and hepatic parameters when compared to the control group. In conclusion, DS12 emerged as an important multitarget compound capable of preventing neurochemical changes associated with memory deficits.

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Acknowledgments

The authors tank veterinarian doctor Anelize de Oliveira Campello Felix for helping with animal experimentation.

Funding

This research was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação de Amparo à Pesquisa do Rio Grande do Sul (FAPERGS—PRONEM processo: 16/2551–0000 2452). This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-Brasil (CAPES)—Finance code 001. W. C. and R. M. S. are recipients of the CNPq fellowship.

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Authors and Affiliations

  1. Laboratório de Química Aplicada a Bioativos, Centro Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Pelotas, RS, Brasil

    Daniel Schuch da Silva & Wilson Cunico

  2. Laboratório de Neuroquímica, Inflamação e Câncer, Centro de Ciências Químicas Farmacêuticas e de Alimentos, Universidade Federal de Pelotas, Campus Universitário s/n, Capão do Leão, RS, CEP 96010-900, Brazil

    Mayara Sandrielly Pereira Soares, Fernanda Cardoso Teixeira, Júlia Eisenhardt de Mello, Anita Avila de Souza, Karina Pereira Luduvico & Roselia Maria Spanevello

  3. Departamento de Clínica de Pequenos Animais, Laboratório de Análises Clínicas Veterinário, Hospital Veterinário, Universidade Federal de Santa Maria, Santa Maria, RS, Brasil

    Cinthia Melazzo de Andrade

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  1. Daniel Schuch da Silva
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Correspondence to Roselia Maria Spanevello or Wilson Cunico.

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All animal experimental protocols were approved by the Committee of Ethics and Animal Experimentation of the Federal University of Pelotas, RS, Brazil (protocol number: CEEA 46528-2018).

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da Silva, D.S., Soares, M.S.P., Teixeira, F.C. et al. Multitarget Effect of 2-(4-(Methylthio)phenyl)-3-(3-(piperidin-1-yl)propyl)thiazolidin-4-one in a Scopolamine-Induced Amnesic Rat Model. Neurochem Res 46, 1554–1566 (2021). https://doi.org/10.1007/s11064-021-03295-0

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