Next Article in Journal
Cytokinin Detection during the Dictyostelium discoideum Life Cycle: Profiles Are Dynamic and Affect Cell Growth and Spore Germination
Previous Article in Journal
Dithiocarbamate as a Valuable Scaffold for the Inhibition of Metallo-β-Lactmases
Previous Article in Special Issue
Synthesis of β-d-galactopyranoside-Presenting Glycoclusters, Investigation of Their Interactions with Pseudomonas aeruginosa Lectin A (PA-IL) and Evaluation of Their Anti-Adhesion Potential
Open AccessCommunication

2-Hydroxy-N-phenylbenzamides and Their Esters Inhibit Acetylcholinesterase and Butyrylcholinesterase

1
Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic
2
Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentská 573, 532 10 Pardubice, Czech Republic
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(11), 698; https://doi.org/10.3390/biom9110698
Received: 16 September 2019 / Revised: 25 October 2019 / Accepted: 1 November 2019 / Published: 5 November 2019
The development of novel inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) represents a viable approach to alleviate Alzheimer’s disease. Thirty-six halogenated 2-hydroxy-N-phenylbenzamides (salicylanilides) with various substitution patterns and their esters with phosphorus-based acids were synthesized in yields of 72% to 92% and characterized. They were evaluated for in vitro inhibition of AChE from electric eel and BuChE from equine serum using modified Ellman’s spectrophotometric method. The benzamides exhibited a moderate inhibition of AChE with IC50 values in a narrow concentration range from 33.1 to 85.8 µM. IC50 values for BuChE were higher (53.5–228.4 µM). The majority of derivatives inhibit AChE more efficiently than BuChE and are comparable or superior to rivastigmine—an established cholinesterases inhibitor used in the treatment of Alzheimer’s disease. Phosphorus-based esters especially improved the activity against BuChE with 5-chloro-2-{[4-(trifluoromethyl)phenyl]carbamoyl}phenyl diethyl phosphite 5c superiority (IC50 = 2.4 µM). This derivative was also the most selective inhibitor of BuChE. It caused a mixed inhibition of both cholinesterases and acted as a pseudo-irreversible inhibitor. Several structure-activity relationships were identified, e.g., favouring esters and benzamides obtained from 5-halogenosalicylic acids and polyhalogenated anilines. Both 2-hydroxy-N-phenylbenzamides and esters share convenient physicochemical properties for blood-brain-barrier penetration and thus central nervous system delivery. View Full-Text
Keywords: acetylcholinesterase; benzamides; butyrylcholinesterase; enzyme inhibition; esters; in vitro inhibition; phosphorus derivatives; salicylanilides acetylcholinesterase; benzamides; butyrylcholinesterase; enzyme inhibition; esters; in vitro inhibition; phosphorus derivatives; salicylanilides
Show Figures

Figure 1

MDPI and ACS Style

Krátký, M.; Štěpánková, Š.; Houngbedji, N.-H.; Vosátka, R.; Vorčáková, K.; Vinšová, J. 2-Hydroxy-N-phenylbenzamides and Their Esters Inhibit Acetylcholinesterase and Butyrylcholinesterase. Biomolecules 2019, 9, 698.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop