A Novel Class of Selective Acetylcholinesterase Inhibitors: Synthesis and Evaluation of (E)-2-(Benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Biological Activities
Entry | R1 | mp (°C) | Yield (%) | Time reaction (min) | IC50a (µM) | Selectivity for AChE | ||
---|---|---|---|---|---|---|---|---|
AChE | BuChE | |||||||
7a | | 209–211 | 84 | 18 | 1274 ± 0.7 | >1870.5 ± 0.6 c | ||
7b | | 241–243 | 87 | 15 | 1179 ± 0.5 | 1396.60 ± 0.8 | ||
7c | | 228–230 | 85 | 17 | 699 ± 0.3 | >1438.3 ± 1.0 c | ||
7d | | 244–246 | 40 | 21 | 504 ± 1.0 | >1439.14 ± 1.0 c | ||
7e | | 190–192 | 80 | 40 | 303 ± 0.8 | >1981.8 ± 0.9 c | ||
7f | | 155–157 | 66 | 18 | 103 ± 0.7 | >2286.3 ± 0.7 c | 22.20 | |
7g | | 185–187 | 59 | 25 | 64 ± 0.6 | 474.05 ± 0.8 | 7.40 | |
7h | | 188–190 | 56 | 26 | >1326.7 ±0.7 c | >1326.75 ± 1.0 c | ||
7i | | 138–140 | 51 | 22 | >1981.80 ± 1.0 c | 1883 ± 0.8 | ||
7j | | 191–193 | 84 | 20 | >1477.45 ± 1.0 c | 1273 ± 0.7 | ||
7k | | 158–160 | 83 | 14 | >1898.90 ± 0.8 c | >1899 ± 0.8 c | ||
Galanthamine | 0.54 ± 0.7 | 8.80 ± 0.5 | 16.29 |
2.3. Kinetic Study
2.4. Molecular Docking
3. Experimental
3.1. General
3.2. Pharmacology
3.2.1. AChE Assay
3.2.2. Kinetic Characterization of AChE Inhibition
3.2.3. Molecular Docking
4. Conclusions
Acknowledgments
- Sample Availability: Samples of the compounds 3a-k are available from the authors.
References
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Torre, P.D.l.; Saavedra, L.A.; Caballero, J.; Quiroga, J.; Alzate-Morales, J.H.; Cabrera, M.G.; Trilleras, J. A Novel Class of Selective Acetylcholinesterase Inhibitors: Synthesis and Evaluation of (E)-2-(Benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles. Molecules 2012, 17, 12072-12085. https://doi.org/10.3390/molecules171012072
Torre PDl, Saavedra LA, Caballero J, Quiroga J, Alzate-Morales JH, Cabrera MG, Trilleras J. A Novel Class of Selective Acetylcholinesterase Inhibitors: Synthesis and Evaluation of (E)-2-(Benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles. Molecules. 2012; 17(10):12072-12085. https://doi.org/10.3390/molecules171012072
Chicago/Turabian StyleTorre, Pedro De la, Luis Astudillo Saavedra, Julio Caballero, Jairo Quiroga, Jans H. Alzate-Morales, Margarita Gutiérrez Cabrera, and Jorge Trilleras. 2012. "A Novel Class of Selective Acetylcholinesterase Inhibitors: Synthesis and Evaluation of (E)-2-(Benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles" Molecules 17, no. 10: 12072-12085. https://doi.org/10.3390/molecules171012072