Next Article in Journal
The Molecular Effects of Sulforaphane and Capsaicin on Metabolism upon Androgen and Tip60 Activation of Androgen Receptor
Next Article in Special Issue
Alignment-Free Method to Predict Enzyme Classes and Subclasses
Previous Article in Journal
Anti-Inflammatory and Anti-Apoptotic Effects of Stybenpropol A on Human Umbilical Vein Endothelial Cells
Previous Article in Special Issue
Prediction Model with High-Performance Constitutive Androstane Receptor (CAR) Using DeepSnap-Deep Learning Approach from the Tox21 10K Compound Library
Open AccessArticle

SAR-mediated Similarity Assessment of the Property Profile for New, Silicon-Based AChE/BChE Inhibitors

1
Institute of Chemistry, University of Silesia, Szkolna 9, 40 007 Katowice, Poland
2
Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 612 42 Brno, Czech Republic
3
Department of Biological and Biochemical Sciences, Faculty of Chemical Technology, University of Pardubice, Studentska 573, 532 10 Pardubice, Czech Republic
4
Division of Biologically Active Complexes and Molecular Magnets, Regional Centre of Advanced Technologies and Materials, Faculty of Science, Palacky University, Slechtitelu 27, 783 71 Olomouc, Czech Republic, [email protected] (J.K.)
5
Department of Molecular Biology and Pharmaceutical Biotechnology, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackeho 1, 612 42 Brno, Czech Republic
6
Global Change Research Institute CAS, Belidla 986/4a, 60300 Brno, Czech Republic
7
Institute of Organic Chemistry and Technology, Faculty of Chemical Technology, University of Pardubice, Studentska 573, 532 10 Pardubice, Czech Republic
8
Department of Energy Saving and Air Protection, Central Mining Institute, Plac Gwarkow 1, 40 166 Katowice, Poland
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(21), 5385; https://doi.org/10.3390/ijms20215385
Received: 15 October 2019 / Revised: 25 October 2019 / Accepted: 27 October 2019 / Published: 29 October 2019
(This article belongs to the Special Issue QSAR and Chemoinformatics Tools for Modeling)
A set of 25 novel, silicon-based carbamate derivatives as potential acetyl- and butyrylcholinesterase (AChE/BChE) inhibitors was synthesized and characterized by their in vitro inhibition profiles and the selectivity indexes (SIs). The prepared compounds were also tested for their inhibition potential on photosynthetic electron transport (PET) in spinach (Spinacia oleracea L.) chloroplasts. In fact, some of the newly prepared molecules revealed comparable or even better inhibitory activities compared to the marketed drugs (rivastigmine or galanthamine) and commercially applied pesticide Diuron®, respectively. Generally, most compounds exhibited better inhibition potency towards AChE; however, a wider activity span was observed for BChE. Notably, benzyl N-[(1S)-2-[(tert-butyldimethylsilyl)oxy]-1-[(2-hydroxyphenyl)carbamoyl]ethyl]-carbamate (2) and benzyl N-[(1S)-2-[(tert-butyldimethylsilyl)oxy]-1-[(3-hydroxyphenyl)carbamoyl]ethyl]-carbamate (3) were characterized by fairly high selective indexes. Specifically, compound 2 was prescribed with the lowest IC50 value that corresponds quite well with galanthamine inhibition activity, while the inhibitory profiles of molecules 3 and benzyl-N-[(1S)-2-[(tert-butyldimethylsilyl)oxy]-1-[(4-hydroxyphenyl)carbamoyl]ethyl]carbamate (4) are in line with rivastigmine activity. Moreover, a structure–activity relationship (SAR)-driven similarity evaluation of the physicochemical properties for the carbamates examined appeared to have foreseen the activity cliffs using a similarity–activity landscape index for BChE inhibitory response values. The ‘indirect’ ligand-based and ‘direct’ protein-mediated in silico approaches were applied to specify electronic/steric/lipophilic factors that are potentially valid for quantitative (Q)SAR modeling of the carbamate analogues. The stochastic model validation was used to generate an ‘average’ 3D-QSAR pharmacophore pattern. Finally, the target-oriented molecular docking was employed to (re)arrange the spatial distribution of the ligand property space for BChE and photosystem II (PSII). View Full-Text
Keywords: silicon-based carbamates; in vitro cholinesterase inhibition; CoMSA; IVE-PLS; molecular docking; similarity-activity landscape index silicon-based carbamates; in vitro cholinesterase inhibition; CoMSA; IVE-PLS; molecular docking; similarity-activity landscape index
Show Figures

Figure 1

MDPI and ACS Style

Bak, A.; Pizova, H.; Kozik, V.; Vorcakova, K.; Kos, J.; Treml, J.; Odehnalova, K.; Oravec, M.; Imramovsky, A.; Bobal, P.; Smolinski, A.; Trávníček, Z.; Jampilek, J. SAR-mediated Similarity Assessment of the Property Profile for New, Silicon-Based AChE/BChE Inhibitors. Int. J. Mol. Sci. 2019, 20, 5385. https://doi.org/10.3390/ijms20215385

AMA Style

Bak A, Pizova H, Kozik V, Vorcakova K, Kos J, Treml J, Odehnalova K, Oravec M, Imramovsky A, Bobal P, Smolinski A, Trávníček Z, Jampilek J. SAR-mediated Similarity Assessment of the Property Profile for New, Silicon-Based AChE/BChE Inhibitors. International Journal of Molecular Sciences. 2019; 20(21):5385. https://doi.org/10.3390/ijms20215385

Chicago/Turabian Style

Bak, Andrzej; Pizova, Hana; Kozik, Violetta; Vorcakova, Katarina; Kos, Jiri; Treml, Jakub; Odehnalova, Klara; Oravec, Michal; Imramovsky, Ales; Bobal, Pavel; Smolinski, Adam; Trávníček, Zdeněk; Jampilek, Josef. 2019. "SAR-mediated Similarity Assessment of the Property Profile for New, Silicon-Based AChE/BChE Inhibitors" Int. J. Mol. Sci. 20, no. 21: 5385. https://doi.org/10.3390/ijms20215385

Find Other Styles
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
Search more from Scilit
 
Search
Back to TopTop