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A novel arylpiperazine derivative (LQFM181) protects against neurotoxicity induced by 3- nitropropionic acid in in vitro and in vivo models. 2024
Hericles Mesquita Campos, and
Robbert Mota Pereira, and
Pâmela Yasmin de Oliveira Ferreira, and
Nkaa Uchenna, and
Cínthia Rio Branco da Silva, and
Letizia Pruccoli, and
Germán Sanz, and
Marcella Ferreira Rodrigues, and
Boniek Gontijo Vaz, and
Bárbara Gonçalves Rivello, and
André Luís Batista da Rocha, and
Flávio Silva de Carvalho, and
Gerlon de Almeida Ribeiro Oliveira, and
Luciano Morais Lião, and
Raphaela de Castro Georg, and
Jacqueline Alves Leite, and
Fernanda Cristina Alcantara Dos Santos, and
Elson Alves Costa, and
Ricardo Menegatti, and
Andrea Tarozzi, and
Paulo César Ghedini
Institute of Biological Sciences, Federal University of Goias, Goiania, GO, Brazil.
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.
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