Hybrids of 4-aminoquinolines and adamantane as inhibitors of AChE
Alzheimer’s disease (AD) is an incurable and progressive neurodegenerative disorder that causes cognitive capabilities and memory loss and damage to brain functionality and structure. From diverse possibilities for drug development, the inhibition of acetylcholinesterase (AChE) remains as dominant t...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Serbian Chemical Society
2025-01-01
|
| Series: | Journal of the Serbian Chemical Society |
| Subjects: | |
| Online Access: | https://doiserbia.nb.rs/img/doi/0352-5139/2025/0352-51392500014K.pdf |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Alzheimer’s disease (AD) is an incurable and progressive neurodegenerative disorder that causes cognitive capabilities and memory loss and damage to brain functionality and structure. From diverse possibilities for drug development, the inhibition of acetylcholinesterase (AChE) remains as dominant treatment of symptoms. In our continued investigation of long-chain derivatives of 4-aminoquinoline containing an adamantyl (Ad) group, six new derivatives that differ in the substitution at the terminal amino group or the Ad moiety were synthesised. Their inhibition of AChE, in silico drug-likeness, the potential for passing through the blood-brain barrier (BBB) and possible binding modes with AChE for the most active compounds were investigated. It was shown that introducing OH, Br or acetamide group increases the inhibitory potency compared with less polar compounds containing the benzyl group as the second substituent at the amino group. Analysis of in silico obtained parameters defined by Lipinsky’s rule showed that neither compound is likely to cross the BBB because of violation of at least one of the rules, in general, log P and a number of rotatable bonds (RB). Docking of the most active compounds to AChE suggests that compounds act as dual-binding site inhibitors since they have simultaneous interaction with catalytic and peripheral anionic sites of AChE. The substituents on the Ad could be the ones that determine the mode of binding into the enzyme and provide interactions that stabilise the complex between the compound and AChE. |
|---|---|
| ISSN: | 0352-5139 1820-7421 |