Structure-activity relationships of sulfonamides derived from carvacrol and their potential for the treatment of Alzheimer's disease

Autor(es)

de Souza, Marcia Maria ^[1] ; Andreolla, Marina Correa ^[1] ; Ribeiro, Thais Cecilia ^[1] ; Goncalves, Ana Elisa ^[1] ; Medeiros, Alex Rogerio ^[2] ; de Souza, Anacleto Silva ^[2] ; Gomes Ferreira, Leonardo Luiz ^[2] ; Andricopulo, Adriano Defini ^[2] ; Yunes, Rosendo Augusto ^[3] ; de Oliveira, Aldo Sena ^{[2, 4]}

Afiliação do(s) autor(es)

^[1] UNIVALI, Grad Program Pharmaceut Sci, Sch Hlth Sci, Rua Uruguai, 458 F6 Lab 206 Campus 1, Itajai, SC 88302 - USA

^[2] Univ Sao Paulo, Lab Med & Computat Chem, Ctr Res & Innovat Biodivers & Drug Discovery, Inst Phys Sao Carlos, Av Joao Dagnone 1100, BR-13563120 Sao Carlos, SP - Brazil

^[3] Univ Fed Santa Catarina, Dept Chem, R Engn Agron Andrei Cristian Ferreira S-N, BR-88040900 Florianopolis, SC - Brazil

^[4] Univ Fed Santa Catarina, Dept Exact Sci & Educ, Campus Blumenau, Rua Joao Pessoa 2750, BR-89036256 Blumenau, SC - Brazil

• Tipo de documento: Artigo Científico
• Fonte: RSC MEDICINAL CHEMISTRY; v. 11, n. 2, p. 307-316, FEB 1 2020.
• Citações Web of Science: 0

Resumo

Five synthetic sulfonamides derived from carvacrol, a natural product and a small molecule with druglike properties, were evaluated with respect to their effects on the cognitive deficits of animals with streptozotocin (STZ)-induced Alzheimer's disease (AD). Memory, ambulation, anxiety and oxidative stress were evaluated. In vitro assays were performed to assess the inhibition of acetylcholinesterase (AChE), and the data were combined with molecular docking for the establishment of structure-activity relationships. The memories of animals treated with the compounds derived from morpholine (1), hydrazine (3) and 2-phenol (5) were improved. Compound 3 was the most promising, yielding excellent results in the inhibitory avoidance test. Moreover, the compounds did not exhibit any deleterious effects on the animals' ambulation in the open field test. Molecular docking confirmed the results obtained in the AChE inhibition assay. In short, compounds 1, 3 and 5 can reduce STZ-induced deficits and show potential for the treatment of Alzheimer's. In addition, these agents produce significant anxiolytic and antioxidant effects. (AU)

• Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
• Beneficiário: Glaucius Oliva
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs