Triazolopyridopyrimidine: A New Scaffold for Dual-Target Small Molecules for Alzheimer’s Disease Therapy
Abstract
:1. Introduction
2. Results
2.1. Synthesis
2.2. Biological Evaluation
2.2.1. Antioxidant Analysis
2.2.2. Inhibition of EeAChE/eqBuChE
2.3. Molecular Modeling
3. Materials and Methods
3.1. Synthesis of Compounds 3a–k
3.2. Biological Evaluation
3.2.1. Oxygen Radical Absorbance Capacity Assay
3.2.2. Inhibition of EeAChE and eqBuChE
3.2.3. Molecular Modeling
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds 3a–k are available from the authors. |
Compound | R1 | R2 | R3 | ORAC a (TE) | % Inhibition of EeAChE b at 10 μM | IC50 (μM) c |
---|---|---|---|---|---|---|
3a | H | H | H | 1.85 ± 0.1 | 40.27 ± 2.4 | nd |
3b | H | CH3 | H | 1.77 ± 0.1 | 73.13 ± 0.1 | 1.17 ± 0.0 |
3c | H | OCH3 | H | 4.01 ± 0.1 | 63.93 ± 1.8 | 1.32 ± 0.0 |
3d | OCH3 | H | H | 4.33 ± 0.1 | 31.23 ± 2.1 | nd |
3e | H | H | OCH3 | 3.79 ± 0.1 | 32.33 ± 2.4 | nd |
3f | H | Cl | H | 1.81 ± 0.1 | 43.90 ± 1.2 | nd |
3g | H | OH | H | 7.17 ± 0.2 | 36.43 ± 0.6 | nd |
3h | H | NO2 | H | 3.54 ± 0.1 | 44.63 ± 1.6 | nd |
3i | H | iPr | H | 1.89 ± 0.1 | 18.17 ± 1 | nd |
3j | H | Br | H | 2.57 ± 0.0 | 38.13 ± 1.1 | nd |
3k | H | OPh | H | 2.99 ± 0.2 | 18.60 ± 1.8 | nd |
Melatonin | - | - | - | 2.45 ± 0.1 | - | - |
Ferulic acid | - | - | - | 3.74 ± 0.2 | - | - |
Tacrine | - | - | - | 95.63 ± 2.1 | 0.03 ± 0.0 |
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Zribi, L.; Pachòn-Angona, I.; Bautista-Aguilera, Ò.M.; Diez-Iriepa, D.; Marco-Contelles, J.; Ismaili, L.; Iriepa, I.; Chabchoub, F. Triazolopyridopyrimidine: A New Scaffold for Dual-Target Small Molecules for Alzheimer’s Disease Therapy. Molecules 2020, 25, 3190. https://doi.org/10.3390/molecules25143190
Zribi L, Pachòn-Angona I, Bautista-Aguilera ÒM, Diez-Iriepa D, Marco-Contelles J, Ismaili L, Iriepa I, Chabchoub F. Triazolopyridopyrimidine: A New Scaffold for Dual-Target Small Molecules for Alzheimer’s Disease Therapy. Molecules. 2020; 25(14):3190. https://doi.org/10.3390/molecules25143190
Chicago/Turabian StyleZribi, Lazhar, Irene Pachòn-Angona, Òscar M. Bautista-Aguilera, Daniel Diez-Iriepa, José Marco-Contelles, Lhassane Ismaili, Isabel Iriepa, and Fakher Chabchoub. 2020. "Triazolopyridopyrimidine: A New Scaffold for Dual-Target Small Molecules for Alzheimer’s Disease Therapy" Molecules 25, no. 14: 3190. https://doi.org/10.3390/molecules25143190