Synthesis and Anticholinesterase Evaluation of Cassine, Spectaline and Analogues

Author(s)

Silva, Marcela C. R. ; Vilela, Adriana F. L. ; Cardoso, Carmen L. L. ; Pilli, Ronaldo A. A.

• Document type: Journal article
• Source: SCIENTIA PHARMACEUTICA; v. 90, n. 4, p. 21-pg., 2022-01-01.

Abstract

In this work, twelve analogues of piperidine alkaloids (-)-cassine and (-)-spectaline were synthesized, as well as the racemic forms of these natural products. The compounds were evaluated for their inhibition of electric eel acetylcholinesterase (AChE(ee)) and human butyrylcholinesterase (BChE(hu)) by on-flow mass-spectrometry-based dual-enzyme assay, and the inhibition mechanisms for the most potent analogues were also determined. Our results showed a preference for BChE(hu) inhibition with compounds 10c (Ki = 5.24 mu M), 12b (Ki = 17.4 mu M), 13a (Ki = 13.2 mu M) and 3 (Ki = 11.3 mu M) displaying the best inhibitory activities. (AU)

• FAPESP's process: 14/50249-8 - Green chemistry: sustainable synthetic methods employing benign solvents, safer reagents, and bio-renewable feedstock
• Grantee: Arlene Gonçalves Corrêa
• Support Opportunities: Research Grants - Research Centers in Engineering Program
• FAPESP's process: 19/13104-5 - Planning and synthesis of inhibitors based on biological targets: the case of neglected kinases
• Grantee: Ronaldo Aloise Pilli
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/02873-0 - Acetylcholinesterase and beta-secretase 1: a study of co-immobilization conditions for screening of ligands
• Grantee: Adriana Ferreira Lopes Vilela
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 16/12541-4 - A biomimetic approach to the total synthesis of Stemona alkaloids
• Grantee: Ronaldo Aloise Pilli
• Support Opportunities: Regular Research Grants