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Structure-Based Search for New Inhibitors of Cholinesterases
Department of Physicochemical Drug Analysis, Faculty of Pharmacy, Medical College, Jagiellonian University, Kraków 30-688, Medyczna 9, Poland
Institute of Pharmacy and Food Chemistry, University of Wuerzburg, Wuerzburg D-97074, Am Hubland, Germany
* Author to whom correspondence should be addressed.
Received: 28 December 2012; in revised form: 31 January 2013 / Accepted: 28 February 2013 / Published: 11 March 2013
Abstract: 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.
Keywords: acetylcholinesterase; butyrylcholinesterase; cholinesterases inhibitors; drug design; fragment-based design
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Bajda, M.; Więckowska, A.; Hebda, M.; Guzior, N.; Sotriffer, C.A.; Malawska, B. Structure-Based Search for New Inhibitors of Cholinesterases. Int. J. Mol. Sci. 2013, 14, 5608-5632.
Bajda M, Więckowska A, Hebda M, Guzior N, Sotriffer CA, Malawska B. Structure-Based Search for New Inhibitors of Cholinesterases. International Journal of Molecular Sciences. 2013; 14(3):5608-5632.
Bajda, Marek; Więckowska, Anna; Hebda, Michalina; Guzior, Natalia; Sotriffer, Christoph A.; Malawska, Barbara. 2013. "Structure-Based Search for New Inhibitors of Cholinesterases." Int. J. Mol. Sci. 14, no. 3: 5608-5632.