N-alkylpiperidine carbamates as potential anti-Alzheimer's agents
Košak, Urban ...
Compounds capable of interacting with single or multiple targets involved in Alzheimer's disease (AD) pathogenesis are potential anti-Alzheimer's agents. In our aim to develop new anti-Alzheimer's ...agents, a series of 36 new N-alkylpiperidine carbamates was designed, synthesized and evaluated for the inhibition of cholinesterases [acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)] and monoamine oxidases [monoamine oxidase A (MAO-A and monoamine oxidase B (MAO-B)]. Four compounds are very promising: multiple AChE (IC50 = 7.31 [micro]M), BChE (IC50 = 0.56 [micro]M) and MAO-B (IC50 = 26.1 [micro]M) inhibitor 10, dual AChE (IC50 = 2.25 [micro]M) and BChE (IC50 = 0.81 [micro]M) inhibitor 22, selective BChE (IC50 = 0.06 [micro]M) inhibitor 13, and selective MAO-B (IC50 = 0.18 [micro]M) inhibitor 16. Results of enzyme kinetics experiments showed that despite the carbamate group in the structure, compounds 10, 13, and 22 are reversible and non-time-dependent inhibitors of AChE and/or BChE. The resolved crystal structure of the complex of BChE with compound 13 confirmed the non-covalent mechanism of inhibition. Additionally, N-propargylpiperidine 16 is an irreversible and time-dependent inhibitor of MAO-B, while N-benzylpiperidine 10 is reversible. Additionally, compounds 10, 13, 16, and 22 should be able to cross the blood-brain barrier and are not cytotoxic to human neuronal-like SH-SY5Y and liver HepG2 cells. Finally, compounds 10 and 16 also prevent amyloid [beta]1-42 (A[beta]1-42)-induced neuronal cell death. The neuroprotective effects of compound 16 could be the result of its A[beta]1[beta]42 anti-aggregation effects.
It was not necessary to add the material to the shelf.
Bibliographic material was successfully added on shelf.
Adding bibliographical material on shelf was not successful.
Material is already on the shelf.
Permalink
URL:
Impact factor
Access to the JCR database is permitted only to users from Slovenia. Your current IP address is not on the list of IP addresses with access permission, and authentication with the relevant AAI accout is required.
Year
Impact factor
Edition
Category
Classification
JCR
SNIP
JCR
SNIP
JCR
SNIP
JCR
SNIP
Select the library membership card:
DRS,
in which the journal is indexed
Database name
Field
Year
Links to authors' personal bibliographies
Links to information on researchers in the SICRIS system
Subject headings in COBISS General List of Subject Headings
Select pickup location
The material from the parent unit is free. If the material is delivered to the pickup location from another unit, the library may charge you for this service.
