A novel arylpiperazine derivative (LQFM181) protects against neurotoxicity induced by 3- nitropropionic acid in in vitro and in vivo models.

Autor: Campos HM; Institute of Biological Sciences, Federal University of Goias, Goiania, GO, Brazil., Pereira RM; Institute of Biological Sciences, Federal University of Goias, Goiania, GO, Brazil., de Oliveira Ferreira PY; Institute of Biological Sciences, Federal University of Goias, Goiania, GO, Brazil., Uchenna N; Institute of Biological Sciences, Federal University of Goias, Goiania, GO, Brazil., Branco da Silva CR; Institute of Biological Sciences, Federal University of Goias, Goiania, GO, Brazil., Pruccoli L; Department of Life Quality Studies, Alma Mater Studiorum - University of Bologna, Rimini, Italy., Sanz G; Chemistry Institute, Federal University of Goias, Goiania, GO, Brazil., Rodrigues MF; Chemistry Institute, Federal University of Goias, Goiania, GO, Brazil., Vaz BG; Chemistry Institute, Federal University of Goias, Goiania, GO, Brazil., Rivello BG; Faculty of Pharmacy, Laboratory of Medicinal Pharmaceutical Chemistry, Federal University of Goias, Goiania, GO, Brazil., Batista da Rocha AL; Faculty of Pharmacy, Laboratory of Medicinal Pharmaceutical Chemistry, Federal University of Goias, Goiania, GO, Brazil., de Carvalho FS; Faculty of Pharmacy, Laboratory of Medicinal Pharmaceutical Chemistry, Federal University of Goias, Goiania, GO, Brazil., Oliveira GAR; Department of Pharmacy, Faculty of Health Sciences, University of Brasilia, Brasilia, DF, Brazil., Lião LM; Chemistry Institute, Federal University of Goias, Goiania, GO, Brazil., Georg RC; Institute of Biological Sciences, Federal University of Goias, Goiania, GO, Brazil., Leite JA; Institute of Biological Sciences, Federal University of Goias, Goiania, GO, Brazil., Dos Santos FCA; Institute of Biological Sciences, Federal University of Goias, Goiania, GO, Brazil., Costa EA; Institute of Biological Sciences, Federal University of Goias, Goiania, GO, Brazil., Menegatti R; Faculty of Pharmacy, Laboratory of Medicinal Pharmaceutical Chemistry, Federal University of Goias, Goiania, GO, Brazil., Tarozzi A; Department of Life Quality Studies, Alma Mater Studiorum - University of Bologna, Rimini, Italy., Ghedini PC; Institute of Biological Sciences, Federal University of Goias, Goiania, GO, Brazil. Electronic address: pcghedini@ufg.br.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2024 May 25; Vol. 395, pp. 111026. Date of Electronic Publication: 2024 Apr 26.
DOI: 10.1016/j.cbi.2024.111026
Abstrakt: In the pursuit of novel antioxidant therapies for the prevention and treatment of neurodegenerative diseases, three new arylpiperazine derivatives (LQFM181, LQFM276, and LQFM277) were synthesized through a molecular hybridization approach involving piribedil and butylated hydroxytoluene lead compounds. To evaluate the antioxidant and neuroprotective activities of the arylpiperazine derivatives, we employed an integrated approach using both in vitro (SH-SY5Y cells) and in vivo (neurotoxicity induced by 3-nitropropionic acid in Swiss mice) models. In the in vitro tests, LQFM181 showed the most promising antioxidant activity at the neuronal membrane and cytoplasmic levels, and significant neuroprotective activity against the neurotoxicity induced by 3-nitropropionic acid. Hence, this compound was further subjected to in vivo evaluation, which demonstrated remarkable antioxidant capacity such as reduction of MDA and carbonyl protein levels, increased activities of succinate dehydrogenase, catalase, and superoxide dismutase. Interestingly, using the same in vivo model, LQFM181 also reduced locomotor behavior and memory dysfunction through its ability to decrease cholinesterase activity. Consequently, LQFM181 emerges as a promising candidate for further investigation into its neuroprotective potential, positioning it as a new therapeutic agent for neuroprotection.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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