Development of substituted benzylidene derivatives as novel dual cholinesterase inhibitors for Alzheimer's treatment.
RSC Adv
; 13(38): 26344-26356, 2023 Sep 04.
Article
in En
| MEDLINE
| ID: mdl-37671344
ABSTRACT
Leading pathological markers of Alzheimer's disease (AD) include Acetylcholinesterase (AChE), Butyrylcholinesterase (BuChE), Amyloid beta (Aß) and reactive oxygen species (ROS). Indole derivatives were identified and optimized to improve the potency against AChE, BuChE, Aß and ROS. The lead molecule IND-30 was found to be selective for AChE (selectivity ratio 22.92) in comparison to BuChE and showed maximum inhibition potential for human AChE (IC50 4.16 ± 0.063 µM). IND-30 was found to be safe on the SH-SY5Y cell line until the dose of 30 mM. Further, molecule IND-30 was evaluated for its ability to inhibit AChE-induced Aß aggregation at 0.5, 10 and 20 µM doses. Approximately, 50% of AChE-induced Aß aggregation was inhibited by IND-30. Thus, IND-30 was found to be multitargeting for AD.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
RSC Adv
Year:
2023
Document type:
Article