Contemporary Anticholinesterase Pharmaceuticals of Natural Origin and Their Synthetic Analogues for the Treatment of Alzheimers Disease
Abstract
Alzheimer's disease (AD), the most common form of dementia, is a degenerative and progressive neurological disorder characterized by deficit in the cholinergic transmission and formation of senile plaques containing beta-amyloid protein in the brain. Although complete pathology of the disease has not been fully elucidated yet, there are several treatment strategies for AD treatment. The complexity of AD is also due to involvement of several enzymes through its progression. Therefore, the most important therapeutic approach has emerged as inhibition of acetylcholinesterase (AChE), which is the key enzyme in the breakdown of acetylcholine. Another very attractive approach to lower beta-amyloid protein in fibrillar form has been the alpha- and beta-secretase inhibitors. On the other hand, recently, N-methyl-D-aspartate (NMDA) receptor antagonists have become a strong alternative, which has been approved to be effective in treatment of moderate to severe type of AD. Within the past few years, some pharmaceuticals have become available for clinical use; however, none of them have been shown to possess ability to discontinue the disease up to date. Hence, there is obviously a great need for discovery of new drug candidates of natural or synthetic origins for AD treatment. This review will cover AChE-inhibiting pharmaceuticals from plants and their synthetic derivatives including relevant patent literatures which may promise a future hope for AD treatment.
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Secondary metabolites such as alkaloids, terpenoids, coumarins, and flavonoids have been reported to have potent AChE inhibitory activity.
“The secondary metabolites of the various classes such as alkaloids, terpenoids, coumarins, flavonoids, etc. have been reported to have potent AChEinhibitory activity [71,72,73,74].”
From Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy (2021) · cites this paper as [74]
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New Acetylcholinesterase Inhibitors for Alzheimer's Disease
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Natural cholinesterase inhibitors from marine organisms
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Self-citationDietary polyunsaturated fatty acids improve cholinergic transmission in the aged brain
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Profiling of in vitro neurobiological effects and phenolic acids of selected endemic Salvia species
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Chemical composition and biological activity of Capparis spinosa L. from Lipari Island
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Orhan, I. E., Atasu, E., Senol, F. S., Ozturk, N., Demirci, B., Das, K., & Sekeroglu, N. (2013) · Industrial Crops and Products · doi:10.1016/j.indcrop.2013.03.022 · Cited by 44 · see citing works
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Coumarins: Auspicious Cholinesterase and Monoamine Oxidase Inhibitors
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Self-citationPlant-derived acetylcholinesterase inhibitory alkaloids for the treatment of Alzheimer's disease
Dall’Acqua, S. (2013) · Botanics Targets and Therapy · doi:10.2147/btat.s17297 · Cited by 37 · see citing works
Orhan, İ. E., Jędrejek, D., Şenol, F. S., Salmas, R. E., Durdağı, S., Kowalska, I., Pecio, Ł., & Oleszek, W. A. (2018) · Phytomedicine · doi:10.1016/j.phymed.2018.03.009 · Cited by 35 · see citing works
Self-citationNamdaung, U., Athipornchai, A., Khammee, T., Kuno, M., & Suksamrarn, S. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.10.019 · Cited by 34 · see citing works
Kumaran, K. R., Yunusa, S., Perimal, E. K., Wahab, H. A., Müller, C. P., & Hassan, Z. (2022) · Journal of Alzheimer s Disease · doi:10.3233/jad-220666 · Cited by 36 · see citing works
Ekin, H. N., Gökbulut, A., Aydın, Z. U., Dönmez, A. A., & Orhan, İ. E. (2016) · Industrial Crops and Products · doi:10.1016/j.indcrop.2016.06.029 · Cited by 33 · see citing works
Self-citationOrhan, İ. E. (2020) · Current Neuropharmacology · doi:10.2174/1570159x18666201119153807 · Cited by 34 · see citing works
Self-citationCurrent anti-Alzheimer’s disease effect of natural products and their principal targets
Zhu, Y., Peng, L., Hu, J., Chen, Y., & Chen, F. (2019) · Journal of Integrative Neuroscience · doi:10.31083/j.jin.2019.03.1105 · Cited by 31 · see citing works
Nature: A Substantial Source of Auspicious Substances with Acetylcholinesterase Inhibitory Action
Orhan, İ. E. (2013) · Current Neuropharmacology · doi:10.2174/1570159x11311040003 · Cited by 29 · see citing works
Self-citationTümen, İ., Şenol, F. S., & Orhan, İ. E. (2012) · Turkish Journal of Biochemistry · doi:10.5505/tjb.2012.92400 · Cited by 29 · see citing works
Self-citationSant'Anna, M. C. B., Soares, V. D. M., Seibt, K. J., Ghisleni, G., Rico, E. P., Rosemberg, D. B., de Oliveira, J. R., Schröder, N., Bonan, C. D., & Bogo, M. R. (2010) · Fish Physiology and Biochemistry · doi:10.1007/s10695-010-9459-7 · Cited by 28 · see citing works
Evaluation of Rosa germplasm resources and analysis of floral fragrance components in R. rugosa
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Gülcan, H. O., Orhan, İ. E., & Şener, B. (2015) · Current Pharmaceutical Biotechnology · doi:10.2174/1389201015666141202105105 · Cited by 27 · see citing works
Self-citationAcetylcholinesterase inhibition by medicinal plants: A Review
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Virtual Screening and Hit Selection of Natural Compounds as Acetylcholinesterase Inhibitors
Atanasova, M., Dimitrov, I., Ivanov, S. M., GEORGIEV, B., Berkov, S. H., Zheleva‐Dimitrova, D., & Doytchinova, I. A. (2022) · Molecules · doi:10.3390/molecules27103139 · Cited by 29 · see citing works
Synthesis and cholinesterase inhibition of cativic acid derivatives
Alza, N. P., Richmond, V., Baier, C. J., Freire, E., Baggio, R., & Murray, A. P. (2014) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2014.06.030 · Cited by 24 · see citing works
Natural Products from Plants and Algae for Treatment of Alzheimer’s Disease: A Review
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Şenol, F. S., Tuzun, C. Y., Toker, G., & Orhan, İ. E. (2012) · International Journal of Food Sciences and Nutrition · doi:10.3109/09637486.2012.676031 · Cited by 23 · see citing works
Self-citationNatural sesquiterpen lactones as acetylcholinesterase inhibitors
HAJIMEHDIPOOR, H., MOSADDEGH, M., NAGHIBI, F., HAERI, A., & HAMZELOO-MOGHADAM, M. (2014) · Anais da Academia Brasileira de Ciências · doi:10.1590/0001-3765201420130005 · Cited by 22 · see citing works
“Physostigmine, galanthamine and huperzine A are the alkaloid-type of compounds isolated from the plants which serve as medicines for AD (Orhan et al. 2009).”
BackgroundŞenol, F. S., Açıkara, Ö. B., Çitoğlu, G. S., Orhan, İ. E., Acqua, S. D., & Özgökçe, F. (2014) · Pharmaceutical Biology · doi:10.3109/13880209.2013.872152 · Cited by 21 · see citing works
Self-citationAn alternative antioxidative and enzyme inhibitory agent from Turkey: Robinia pseudoacacia L.
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Self-citationOrhan, İ. E., Tosun, F., Gülpınar, A. R., Kartal, M., Duran, A., Mıhoğlugil, F., & Akalgan, D. (2014) · Phytochemistry Letters · doi:10.1016/j.phytol.2014.10.003 · Cited by 17 · see citing works
Self-citationErdem, S. A., Şenol, F. S., Budakoglu, E., Orhan, İ. E., & Şener, B. (2015) · Journal of Food and Drug Analysis · doi:10.1016/j.jfda.2015.08.001 · Cited by 14 · see citing works
Self-citationRole of Acetylcholinesterase Inhibitors and Alzheimer Disease
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Karahisar, E., Tuğay, O., Orhan, İ. E., Şenol, F. S., Luca, S. V., Skalicka‐Woźniak, K., & Sahin, M. (2019) · Chemistry & Biodiversity · doi:10.1002/cbdv.201900333 · Cited by 14 · see citing works
Self-citationEmerging paradigms in Alzheimer's therapy
Agnes Preethy, H., Rajendran, K., Sukumar, A. J., & Krishnan, U. M. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176872 · Cited by 14 · see citing works
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Effect of Trigonella foenum-graecum Linn. seeds methanol extract on learning and memory
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Swertiamarin, a secoiridoid glycoside modulates nAChR and AChE activity
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Vitamin B3-Based Biologically Active Compounds as Inhibitors of Human Cholinesterases
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Therapeutic Interventions in Alzheimer Disease
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Self-citationExploring medicinal plants for the development of natural enzyme inhibitors
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Recent Approaches Towards Selected Lamiaceae Plants for Their Prospective Use in Neuroprotection
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Neuromodulatory Effect of Plant Metabolites
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Tris-diamine-derived transition metal complexes of flurbiprofen as cholinesterase inhibitors
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Immunotherapies: A Treasure Trove of Alzheimer's Disease
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Unlocking the Impact of Phyto-bioactive Compounds against Neurodegenerative Disorders
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Bioactive Compounds and Essential Oils as Acetylcholinesterase Inhibitors
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BindingDB Entry 50045214: Synthesis and cholinesterase inhibition of cativic acid derivatives.
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Richetti, S. K. (2010) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
- Authors
- Orhan, G., Orhan, I., Subutay-Oztekin, N., Ak, F., & Sener, B.
- Venue
- Recent Patents on CNS Drug Discovery
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2009-01-01
- Volume
- 4
- Issue
- 1
- Pages
- 43-51
- ISSN
- 1574-8898 (ISSN-L)
- OpenAlex
- W2167292970
- Cited by
- 90
- References
- 99
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 7 · 2023: 1 · 2022: 7 · 2021: 2 · 2020: 5 · 2019: 9 · 2018: 5 · 2017: 2 · 2016: 5 · 2015: 5 · 2014: 8 · 2013: 8 · 2012: 4
- FWCI
- 3.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Recent Patents on CNS Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
- Keywords
- Alzheimer's disease, acetylcholinesterase inhibitors, natural products, plant-derived drugs, synthetic analogues, amyloid-beta, secretase inhibitors, NMDA receptor antagonists, cholinergic neurotransmission, drug discovery, patents
- MeSH terms
- Acetylcholinesterase, Alzheimer Disease, Animals, Cholinesterase Inhibitors, Humans
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