Structure-Based Search for New Inhibitors of Cholinesterases

International Journal of Molecular Sciences

Marek Bajda²  Anna Wiᆜkowska²  Michalina Hebda²  Natalia Guzior²  Christoph A. Sotriffer¹ 

[1] Institute of Pharmacy and Food Chemistry, University of Wuerzburg, Wuerzburg D-97074, Am Hubland, Germany; E-Mail:;Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Medical College, Jagiellonian University, Kraków 30-688, Medyczna 9, Poland; E-Mails:

关键词: acetylcholinesterase;    butyrylcholinesterase;    cholinesterases inhibitors;    drug design;    fragment-based design;   

DOI  :  10.3390/ijms14035608

来源: mdpi

【 摘 要 】

Cholinesterases are important biological targets responsible for regulation of cholinergic transmission, and their inhibitors are used for the treatment of Alzheimer’s disease. To design new cholinesterase inhibitors, of different structure-based design strategies was followed, including the modification of compounds from a previously developed library and a fragment-based design approach. This led to the selection of heterodimeric structures as potential inhibitors. Synthesis and biological evaluation of selected candidates confirmed that the designed compounds were acetylcholinesterase inhibitors with IC₅₀ values in the mid-nanomolar to low micromolar range, and some of them were also butyrylcholinesterase inhibitors.

【 授权许可】

CC BY   
© 2013 by the authors; licensee MDPI, Basel, Switzerland.