Effects of novel acylhydrazones derived from 4-quinolone on the acetylcholinesterase activity and A beta 42 peptide fibrils formation

Autor(es)

da Silva, Gisele S. ; Figueiro, Micheli ; Tormena, Claudio F. ; Coelho, Fernando ; Almeida, Wanda P.

• Tipo de documento: Artigo Científico
• Fonte: Journal of Enzyme Inhibition and Medicinal Chemistry; v. 31, n. 6, p. 1464-1470, 2016.
• Citações Web of Science: 4

Resumo

Acetylcholinesterase inhibitors and compounds that trigger Ab amyloid oligomerization and fibrillization represent an opportunity to discover new drug candidates to treat Alzheimer's disease. In this work, we synthesized nine new acylhydrazones and a known one, both employing 3-carboethoxy-4-quinolone derivatives as starting materials with chemical yields ranging from 63% to 90%. We evaluated the effect of these compounds on the acetylcholinesterase (AChE) activity and the fibrillization of A beta(42) peptide. Except for one acylhydrazone, the compounds exhibited good inhibitory effect on AChE (1.2 mu M < IC50 values < 17 mu M). They also showed a significant decrease in the thioflavin-T fluorescence emission, suggesting an inhibitory effect on the A beta(42) fibril formation. (AU)

• Processo FAPESP: 13/18203-5 - Síntese de híbridos moleculares derivados de 4-quinolonas candidatos a fármacos para a Doença de Alzheimer
• Beneficiário: Wanda Pereira Almeida
• Modalidade de apoio: Auxílio à Pesquisa - Regular