Homarine Alkyl Ester Derivatives as Promising Acetylcholinesterase Inhibitors

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Joao, KG (Author) Other; Videira, RA (Author) Other; Fatima Paiva Martins (Author) FCUP; Patricia Valentao (Author) FFUP; David M Pereira (Author) FFUP; Paula B Andrade (Author) FFUP

Journal

Title: ChemMedChem

Vol. 16

Pages: 3315-3325

ISSN: 1860-7179

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 0 Citations

Scopus - 1 Citation

Other information

Authenticus ID: P-00V-C0H

DOI: 10.1002/cmdc.202100265

Abstract (EN): Reversible acetylcholinesterase (AChE) inhibitors are key therapeutic tools to modulate the cholinergic connectivity compromised in several degenerative pathologies. In this work, four alkyl esters of homarine were synthesized and screened by using Electrophorus electricus AChE and rat brain AChE-rich fraction. Results showed that all homarine alkyl esters are able to inhibit AChE by a competitive inhibition mode. The effectiveness of AChE inhibition increases with the alkyl side chain length of the homarine esters, being HO-C-16 (IC50=7.57 +/- 3.32 mu M and K-i=18.96 +/- 2.28 mu M) the most potent inhibitor. The fluorescence quenching studies confirmed that HO-C-16 is the compound with higher selectivity and affinity for the tryptophan residues in the catalytic active site of AChE. Preliminary cell viability studies showed that homarine esters display no toxicity for human neuronal SH-SY5Y cells. Thus, the long-chain homarine esters emerge as new anti-cholinesterase agents, with potential to be considered for therapeutic applications development.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11