From BACE1 Inhibitor to Multifunctionality of Tryptoline and Tryptamine Triazole Derivatives for Alzheimer’s Disease
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis
2.2. Chemical and Biological Assays
Cpd | Log P | BACE1 | Anti-Aβ aggregation | Fe chelation | DPPH | ||||
---|---|---|---|---|---|---|---|---|---|
% Inhibition (at 25 µM) (±SEM) | IC50 (µM) | % Inhibition (at 100 µM) (±SEM) | IC50 (µM) | % Capacity (at 100 µM) (±SEM) | Stoichio-metric ratio (Fe:cpd) | % Inhibition (at 100 µM) (±SEM) | IC50 (µM) | ||
6a | 4.69 | 67.95 (±0.35) | 19.82 | NA | - | 9.67 (±0.32) | - | NA | - |
6b a | 3.86 | 73.63 (±1.47) | 18.86 | 7.19 (±1.19) | - | 12.35 (±0.68) | - | NA | - |
6c | 4.10 | 78.91 (±2.83) | 18.03 | 10.12 (±0.86) | - | 15.88 (±0.21) | - | NA | - |
6d | 3.01 | 14.10 (±1.79) | - | NA | - | 32.86 (±0.19) | - | 2.81 (±0.37) | - |
6e | 2.16 | 12.57 (±1.10) | - | NA | - | 20.63 (±0.35) | - | 5.45 (±0.33) | - |
6f | 1.41 | 21.28 (±1.92) | - | NA | - | 5.80 (±0.04) | - | NA | - |
6g | 2.01 | 21.14 (±1.13) | - | 66.36 (±2.02) | 82.90 | 8.88 (±0.25) | - | 47.03 (±0.12) | 106.41 |
6h | 1.75 | 21.72 (±0.33) | - | 84.13 (±2.49) | 29.86 | 42.74 (±0.30) | 1:3 | 92.29 (±0.02) | 42.91 |
12a | 4.42 | 18.91 (±0.40) | - | 17.81 (±0.86) | - | 42.65 (±1.07) | - | NA | - |
12b | 3.58 | 30.42 (±3.54) | - | 34.02 (±10.13) | - | 10.54 (±0.22) | - | NA | - |
12c | 3.83 | 61.46 (±1.83) | 20.75 | 67.56 (±0.72) | 83.23 | 60.90 (±0.51) | 1:3 | NA | - |
12d | 2.73 | 32.97 (±0.37) | - | 82.52 (±1.26) | 47.51 | 13.87 (±0.59) | - | 1.56 (±0.51) | - |
12e | 1.88 | 7.53 (±1.79) | - | 36.03 (±1.92) | - | 41.42 (±1.13) | - | NA | - |
12f | 1.13 | 16.57 (±2.91) | - | 3.80 (±1.56) | - | 13.06 (±0.16) | - | 1.32 (±0.78) | - |
12g | 1.74 | 16.23 (±0.45) | - | 46.06 (±1.63) | 109.83 | 77.70 (±0.67) | 1:3 | 40.79 (±0.31) | 130.44 |
12h | 1.47 | 40.03 (±0.95) | - | 81.48 (±2.54) | 56.39 | 66.45 (±0.37) | 1:3 | 50.58 (±0.17) | 92.70 |
Inh IV (Merck®) | 1.23 | 96.51 (±1.33) | 0.015 b | - | - | - | - | - | - |
Curcumin | 2.56 | - | - | 82.90 (±0.82) | 0.63c | - | - | - | - |
EDTA | −2.69 | - | - | - | - | 98.00 (±0.34) | - | - | |
Ascorbic acid | −3.36 | - | - | - | - | - | - | 53.64 (±0.11) | 94.92 |
3. Experimental
3.1. General
3.2. Docking Study of β-Secretase (BACE1)
3.3. Docking Study of Amyloid β (Aβ)
3.4. Preparation of Azidomethyl Tryptamine Intermediates
3.5. Preparation of Alkynes d–h
3.6. Preparation of Triazolylmethyl Tryptolines 6a–i and Triazolylmethyl Tryptamines 12a–h
3.7. β-Secretase inhibition assay
3.8. Cathepsin D assay
3.9. Amyloid β Preparation and Aggregation Assay
3.10. Fe (II) Chelation Capcity Assay
3.11. Free Radical Scavenging Assay
3.12. Cell Culture and Cell Viability Assay by MTT method
4. Conclusions
Acknowledgments
Conflict of Interest
References
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Jiaranaikulwanitch, J.; Govitrapong, P.; Fokin, V.V.; Vajragupta, O. From BACE1 Inhibitor to Multifunctionality of Tryptoline and Tryptamine Triazole Derivatives for Alzheimer’s Disease. Molecules 2012, 17, 8312-8333. https://doi.org/10.3390/molecules17078312
Jiaranaikulwanitch J, Govitrapong P, Fokin VV, Vajragupta O. From BACE1 Inhibitor to Multifunctionality of Tryptoline and Tryptamine Triazole Derivatives for Alzheimer’s Disease. Molecules. 2012; 17(7):8312-8333. https://doi.org/10.3390/molecules17078312
Chicago/Turabian StyleJiaranaikulwanitch, Jutamas, Piyarat Govitrapong, Valery V. Fokin, and Opa Vajragupta. 2012. "From BACE1 Inhibitor to Multifunctionality of Tryptoline and Tryptamine Triazole Derivatives for Alzheimer’s Disease" Molecules 17, no. 7: 8312-8333. https://doi.org/10.3390/molecules17078312