Synthesis, biological evaluation, and computational studies of N-benzyl pyridinium-curcumin derivatives as potent AChE inhibitors with antioxidant activity.
J Enzyme Inhib Med Chem
; 38(1): 2281264, 2023 Dec.
Article
de En
| MEDLINE
| ID: mdl-37985494
ABSTRACT
A library of N-benzylpyridinium-based compounds, 7a-j and 8a-j, was designed and synthesised as potential acetylcholinesterase) AChE (inhibitors. An in vitro assay for the synthesised compounds showed that most compounds had significant AChE inhibitory activities at the nanomolar and submicromolar levels. The benzyl (8a) and fluoro (8b) derivatives were the most active, with IC50 values ≤56 nM. Compound 7f, which had a benzyl moiety, showed the highest potency among all the target compounds, with an IC50 value of 7.5 ± 0.19 nM against AChE, which was higher than that of the activities of tacrine (IC50 = 30 ± 0.2 nM) and donepezil (IC50 = 14 ± 0.12 nM). Compounds with vanillin moieties exhibited antioxidant activity. Among the tested compounds, four derivatives (7f, 7 g, 8f, and 8 g) exhibited superior AChE inhibitory activity, with Ki values of 6-16 nM, which were potent in the same range as the approved drug, donepezil. These compounds showed moderate antioxidant activities, as indicated by the results of the ABTS assay.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Curcumine
/
Maladie d'Alzheimer
Limites:
Humans
Langue:
En
Journal:
J Enzyme Inhib Med Chem
Sujet du journal:
BIOQUIMICA
/
QUIMICA
Année:
2023
Type de document:
Article
Pays d'affiliation:
Jordanie