MyJournals Home  

RSS FeedsPharmaceuticals, Vol. 15, Pages 1220: Design, Synthesis and Biological Evaluation of Biscarbamates as Potential Selective Butyrylcholinesterase Inhibitors for the Treatment of Alzheimer’s Disese (Pharmaceuticals)

 
 

30 september 2022 18:14:13

 
Pharmaceuticals, Vol. 15, Pages 1220: Design, Synthesis and Biological Evaluation of Biscarbamates as Potential Selective Butyrylcholinesterase Inhibitors for the Treatment of Alzheimer’s Disese (Pharmaceuticals)
 


As butyrylcholinesterase (BChE) plays a role in the progression of symptoms and pathophysiology of Alzheimer’s disease (AD), selective inhibition of BChE over acetylcholinesterase (AChE) can represent a promising pathway in treating AD. The carbamate group was chosen as a pharmacophore because the carbamates currently or previously in use for the treatment of AD displayed significant positive effects on cognitive symptoms. Eighteen biscarbamates with different substituents at the carbamoyl and hydroxyaminoethyl chain were synthesized, and their inhibitory potential toward both cholinesterases and inhibition selectivity were determined. The ability of carbamates to cross the blood–brain barrier (BBB) by passive transport, their cytotoxic profile and their ability to chelate biometals were also evaluated. All biscarbamates displayed a time-dependent inhibition with inhibition rate constants within 10−3–10−6 M−1 min−1 range for both cholinesterases, with generally higher preference to BChE. For two biscarbamates, it was determined that they should be able to pass the BBB by passive transport, while for five biscarbamates, this ability was slightly limited. Fourteen biscarbamates did not exhibit a cytotoxic effect toward liver, kidney and neuronal cells. In conclusion, considering their high BChE selectivity, non-toxicity, ability to chelate biometals and pass the BBB, compounds 2 and 16 were pointed out as the most promising compounds for the treatment of middle and late stages of AD.


 
74 viewsCategory: Medicine, Pharmacology
 
Pharmaceuticals, Vol. 15, Pages 1219: A Review of the Biological Activity of Amidrazone Derivatives (Pharmaceuticals)
Pharmaceuticals, Vol. 15, Pages 1221: Phytochemical Profiling, Antioxidant, Antimicrobial and Cholinesterase Inhibitory Effects of Essential Oils Isolated from the Leaves of Artemisia scoparia and Artemisia absinthium (Pharmaceuticals)
 
 
blog comments powered by Disqus


MyJournals.org
The latest issues of all your favorite science journals on one page

Username:
Password:

Register | Retrieve

Search:

Pharmacology


Copyright © 2008 - 2022 Indigonet Services B.V.. Contact: Tim Hulsen. Read here our privacy notice.
Other websites of Indigonet Services B.V.: Nieuws Vacatures News Tweets Nachrichten