INVESTIGADORES
MURRAY Ana paula
artículos
Título:
New photochromic azoderivatives with potent acetylcholinesterase inhibition
Autor/es:
BISCUSSI, BRUNELLA; SEQUEIRA, MARIA ALEJANDRA; RICHMOND, VICTORIA; ARROYO MAÑEZ, PAU; MURRAY, ANA PAULA
Revista:
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY
Editorial:
ELSEVIER SCIENCE SA
Referencias:
Año: 2021 vol. 418 p. 113375 - 113375
ISSN:
1010-6030
Resumen:
The design of photochromic cholinesterase inhibitors is a challenge of the photopharmacological approach towards the remote control of acetylcholinesterase (AChE) enzyme and its potential application in Alzheimer´s disease therapy. In this work, a series of azoderivatives were designed, synthesized and evaluated as AChE inhibitors. The optimized microwave-assisted synthesis (two steps) showed excellent yields with a total reaction time no longer than 40 min. The results showed that all the synthesized compounds exhibited high AChE inhibitory activity at the micromolar range (IC50, 0.65?8.52 μM). Moreover, compound 19, with double four-hydrocarbon chain connected to piperidine, showed a powerful in vitro enzymatic response for its Z isomer (IC50: 0.43 μM) determined by Ellman´s assay. Also, 19 showed a stable photostationary state monitored by UV/Vis absorption spectroscopy and 1H NMR spectra. These results indicate that 19 can act as an efficient photo-responsible probe to remote control AChE activity. Molecular modelling analysis of 19 Z revealed its affinity by the peripheral anionic site of AChE, providing understanding of its higher inhibition power. This study contributes to the development of new promising agents for photopharmacological treatment of Alzheimer´s disease.