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

Author(s)

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

• Document type: Journal article
• Source: Journal of Enzyme Inhibition and Medicinal Chemistry; v. 31, n. 6, p. 1464-1470, 2016.
• Web of Science Citations: 4

Abstract

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)

• FAPESP's process: 13/18203-5 - Synthesis of molecular hybrids derived from 4-quinolones as potential drug candidates to treat Alzheimer's Disease
• Grantee: Wanda Pereira Almeida
• Support Opportunities: Regular Research Grants