Natural Alkaloids as Multi-Target Compounds towards Factors Implicated in Alzheimer’s Disease
Abstract
:1. Introduction
2. Plant Alkaloids as Multi-Target Compounds for the Treatment of AD
2.1. Indole Alkaloids: Ajmalicine and Reserpine
2.2. β-Carboline Alkaloids: Harmine and Harmaline
2.3. Protoberberine Alkaloids: Berberine and Palmatine
2.4. Benzophenathridine Alkaloids: Avicine, Nitidine, and Chelerythrine
3. Marine Alkaloids and Nitrogen Containing Compounds as Multi-Target Compounds for the Treatment of AD
3.1. Imidazole Alkaloids: Pseudozoanthoxanthin and Stevensine
3.2. Indole Alkaloids: Meridianins
3.3. Further Nitrogen Containing Marine Compounds as Multi-Target Compounds for the Treatment of AD: Pulmonarin B
3.4. Quinazoline-Benzodiazepine Alkaloid: Circumdatin D
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound | AChE IC50 (µM) | BuChE IC50 (µM) | BACE-1 (% Inhibition at Given Conc.) | Aβ1–42 IC50 (µM) | MAO-A IC50 (µM) | CDK5 IC50 (µM) | GSK-3β IC50 (µM) | DYRK1A IC50 (µM) | PAMPA BBB Permeation Pe (×10−6 cm/s) | Ref. |
---|---|---|---|---|---|---|---|---|---|---|
Harmine | 1.21 ± 0.04 b; 9.05 ± 1.08 b | 2.79 ± 0.27 d; 75.07 ± 1.29 d | 0 ± 13 at 10 µM | 2.5 ± 0.7 | 0.38 ± 0.21 | 20 | 31.1 ± 1.0 | 0.080 ± 0.007 | 44.6 (CNS+); 7.17 ± 1.29 (CNS+) | [70,71,72,73,74,75,76] |
Harmaline | 1.95 ± 0.08 b; 10.58 ± 2.01 b | 5.38 ± 0.64 d; 101.39 ± 1.39 d | n.d. | n.d. | 0.10 ± 0.08 | Inhibition 7% at 50 µM | n.d. | 9 | n.d. | [70,72,76,77,78] |
ZDWX-25 | n.d. | n.d. | n.d. | n.d. | n.d. | n.d. | 0.071 ± 0.009 | 0.103 ± 0.004 | 16.5 (CNS+) | [71] |
Reserpine | 1.7 ± 2.08 b | 2.8 ± 1.84 d | 47 at 50 µM | 57% at 44 µM | Increase in activity | n.d. | n.d. | n.d. | 2.75 ± 0.25 (CNS+/−) | [68,75,79] |
Ajmalicine | 3.5 ± 1.41 b | 5.44 ± 1.75 d | 69 at 50 µM | 69% at 44 µM | n.d. | n.d. | n.d. | n.d. | n.d. | [68] |
Berberine | 0.520 ± 0.042 a; 0.61 ± 0.04 a; 0.7 ± 0.1 a; 0.44 ± 0.04 b; 2.74 ± 0.22 b | 30.7 ± 3.5 c; 6.40 ± 0.29 d; 3.44 ± 0.26 d | IC50 > 100 µM | 43.84 ± 6.09 | 126 | n.d. | n.d. | n.d. | 0.1 ± 0.1 (CNS−); 0.02 (CNS−) | [80,81,82,83,84,85,86] |
Palmatine | 0.46 ± 0.013 a; 1.69 ± 0.11 a; 4.07 ± 0.09 b; 0.51 ± 0.00 b | >100 c; 6.84 ± 0.07 d | IC50 > 100 µM | 92.15 ± 3.42 | 63.86 ± 1.35 | n.d. | n.d. | n.d. | 0 (CNS−) | [80,81,82,83,85,87] |
Avicine | 0.52 ± 0.05 a; 0.15 ± 0.01 b | 0.88 ± 0.08 d | n.d. | 5.56 ± 0.94 | 0.41 ± 0.02 | n.d. | n.d. | n.d. | n.d. | [86] |
Nitidine | 1.25 ± 0.09 a; 0.65 ± 0.09 b | 5.73 ± 0.60 d | n.d. | 1.89 ± 0.40 | 1.89 ± 0.17 | n.d. | n.d. | n.d. | n.d. | [86] |
Chelerythrine | 1.54 ± 0.07 a; 1.03 ± 0.11 b | 10.34 ± 0.24 c; 3.55 ± 0.18 d | n.d. | 4.20 ± 0.43 | 0.55 ± 0.042 | n.d. | 0% at 10 µM | n.d. | 3.25 (CNS+/−) | [82,85,86,88,89] |
Compound | AChE IC50 (µM) | BuChE IC50 (µM) | BACE-1 IC50 (µM) | Aβ1–42 (% Inhibition at Given Conc.) | DYRK1A IC50 (µM) | Ref. |
---|---|---|---|---|---|---|
Pseudozoanthoxanthin | 12.2 ± 1.4 a | 14.6 ± 5.4 c | 0.9 ± 0.1 | 50% at 50 µM | n.d. | [143] |
Stevensine | 7.8 ± 1.5 a | 141.6 ± 34.0 c | 1.4 ± 0.4 | n.d. | n.d. | [143] |
Hymenialdisine | n.d. | n.d. | n.d. | n.d. | 0.0033 | [149] |
Pulmonarin B | 37.02 ± 2.11 b | 30.70 ± 1.44 c | n.d. | 29.78 ± 1.45% at 10 µM | n.d. | [150] |
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Vrabec, R.; Blunden, G.; Cahlíková, L. Natural Alkaloids as Multi-Target Compounds towards Factors Implicated in Alzheimer’s Disease. Int. J. Mol. Sci. 2023, 24, 4399. https://doi.org/10.3390/ijms24054399
Vrabec R, Blunden G, Cahlíková L. Natural Alkaloids as Multi-Target Compounds towards Factors Implicated in Alzheimer’s Disease. International Journal of Molecular Sciences. 2023; 24(5):4399. https://doi.org/10.3390/ijms24054399
Chicago/Turabian StyleVrabec, Rudolf, Gerald Blunden, and Lucie Cahlíková. 2023. "Natural Alkaloids as Multi-Target Compounds towards Factors Implicated in Alzheimer’s Disease" International Journal of Molecular Sciences 24, no. 5: 4399. https://doi.org/10.3390/ijms24054399