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Vol. 12 No. 3 (2024): 2024 Volume -12 - Issue 3

Copyright (c) 2024 Nashwa K.K, K. Anuja

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Chalcones as Modulators of Neurodegenerative Processes: Exploring Their Role in Alzheimer's and Parkinson's Diseases

https://doi.org/10.61096/ijamscr.v12.iss3.2024.340-353
Nashwa K.K
Department of pharmaceutical chemistry, Al Shifa college of pharmacy, kizhattur, perinthalmanna-679325, Kerala, India.
K. Anuja
Department of pharmaceutical chemistry, Al Shifa college of pharmacy, kizhattur, perinthalmanna-679325, Kerala, India.

Corresponding Author(s) : Nashwa K.K

[email protected]

International Journal of Allied Medical Sciences and Clinical Research, Vol. 12 No. 3 (2024): 2024 Volume -12 - Issue 3

Abstract

Neurodegenerative diseases such as Alzheimer's and Parkinson's present a significant global health challenge due to their increasing prevalence and the lack of effective treatments. Chalcones, a class of natural flavonoids, have emerged as promising therapeutic agents due to their diverse biological activities, including antioxidant, anti-inflammatory, and enzyme inhibitory properties. This review comprehensively examines the role of chalcones as modulators of neurodegenerative processes, focusing on their potential therapeutic applications in Alzheimer's and Parkinson's diseases. We explore the molecular mechanisms underlying chalcone activity, including the inhibition of key enzymes like monoamine oxidases (MAOs) and acetylcholinesterase (AChE), as well as their impact on amyloid-beta aggregation, tau phosphorylation, and neuroinflammation. Additionally, we highlight recent advances in structure–activity relationship (SAR) studies that have led to the development of potent chalcone derivatives with enhanced neuroprotective properties. We also discusses the therapeutic potential and limitations of chalcones, providing insights into future research directions for the development of chalcone-based treatments for neurodegenerative diseases.

Keywords

Chalcones Neurodegenerative disease monoamine oxidases acetyl cholinesterase Structural activity relationship
References
  1. Lipton, S.A. The molecular basis of memantine action in Alzheimer’s disease and other neurologic disorders: Low-affinity, Uncompetitive antagonism. Curr. Alzheimer Res. 2005, 2, 155–165.
  2. 2.Van Bulck, M.; Sierra-Magro, A.; Alarcon-Gil, J.; Perez-Castillo, A.; Morales-Garcia, J.A. Novel Approaches for the Treatment of Alzheimer’s and Parkinson’s Disease. Int. J. Mol. Sci. 2019, 20, 719.
  3. Ball N, Teo W-P, Chandra S, Chapman J (2019) Parkinson’s dis ease and the environment. Front Neurol 10:218
  4. Shimohama S, Sawada H, Kitamura Y, Taniguchi T (2003) Dis ease model: Parkinson’s disease. Trends Mol Med 9(8):360–365.
  5. Di Monte DA (2003) The environment and Parkinson’s disease: is the nigrostriatal system preferentially targeted by neurotoxins? Lancet Neurol 2(9):531–538
  6. Emamzadeh FN, Surguchov A (2018) Parkinson’s disease: bio markers, treatment, and risk factors. Front Neurosci 12:612
  7. Agnihotri A, Aruoma OI (2020) Alzheimer’s disease and Parkin son’s disease: a nutritional toxicology perspective of the impact of oxidative stress, mitochondrial dysfunction, nutrigenomics and environmental chemicals. J Am Coll Nutr 39(1):16–27
  8. Quinteros E, Ribó A, Mejía R, López A, Belteton W, Comandari A et al (2017) Heavy metals and pesticide exposure from agricul tural activities and former agrochemical factory in a Salvadoran rural community. Environ Sci Pollut Res 24(2):1662–1676.
  9. Breijyeh, Z., & Karaman, R. (2020). Comprehensive Review on Alzheimer's Disease: Causes and Treatment. Molecules (Basel, Switzerland), 25(24), 5789.
  10. Arash Shakeri, Praveen P. Nekkar Rao, University of Waterloo, Waterloo, ON, Canada Evaluation of novel adamantane derivatives as potential dual inhibitors of amyloid beta and tau aggregation.
  11. Bloem BR, Okun MS, Klein C (2021) Parkinson’s disease. The Lancet 397(10291):2284–2303.
  12. Sveinbjornsdottir S (2016) The clinical symptoms of Parkinson’s disease. J Neurochem 139:318–324.
  13. Randall AD, Witton J, Booth C, Hynes-Allen A, Brown JT. The functional neurophysiology of the amyloid precursor protein (APP) processing pathway. Neuropharmacology. 2010; 59(4–5):243– 267. [PubMed: 20167227]
  14. Tiraboschi P, Hansen LA, Thal LJ, Corey-Bloom J. The importance of neuritic plaques and tangles to the development and evolution of AD. Neurology. 2004; 62(11):1984–1989. [PubMed: 15184601].
  15. Selkoe DJ. Alzheimer’s disease results from the cerebral accumulation and cytotoxicity of amyloid beta-protein. J Alzheimers Dis. 2001; 3(1):75–80. [PubMed: 12214075]
  16. Tanzi RE, Bertram L. Twenty years of the Alzheimer’s disease amyloid hypothesis: a genetic perspective. Cell. 2005; 120(4):545–555. [PubMed: 15734686]
  17. Huang X, Moir RD, Tanzi RE, Bush AI, Rogers JT. Redox-active metals, oxidative stress, and Alzheimer’s disease pathology. Ann NY Acad Sci. 2004; 1012:153–163. [PubMed: 15105262].
  18. C. Cheignon, M. Tomas, D. Bonnefont-Rousselot, P. Faller, C. Hureau, F. Collin, Oxidative stress and the amyloid beta peptide in Alzheimer's disease, Redox Biol. 14 (2018) 450e464.
  19. A. Spinello, R. Bonsignore, G. Barone, B.K. Keppler, A. Terenzi, Metal ions and metal complexes in Alzheimer's disease, Curr. Pharmaceut. Des. 22 (26) (2016) 3996e4010.
  20. S.L. Sensi, A. Granzotto, M. Siotto, R. Squitti, Copper and Zinc dysregulation in Alzheimer's disease, Trends Pharmacol. Sci. 39 (12) (2018), 1049-1046
  21. A.M. Pazini, G.M. Gomes, J.G. Villarinho, C. da Cunha, F. Pinheiro, A.P. Ferreira, C.F. Mello, J. Ferreira, M.A. Rubin, Selegiline reverses ab25-35-induced cognitive deficit in male mice, Neurochem. Res.2013; 38(11): 2287e2294.
  22. Hayes MT (2019) Parkinson’s disease and parkinsonism. Am J Med 132(7):802–807
  23. Skogar O, Nilsson M (2018) Distribution of non-motor symptoms in idiopathic Parkinson’s disease and secondary Parkinsonism. J Multidiscip Healthc 11:525.
  24. Surmeier DJ (2018) Determinants of dopaminergic neuron loss in Parkinson’s disease. FEBS J 285(19): 3657–3668
  25. Latif S, Jahangeer M, Razia DM, Ashiq M, Ghafar A, Akram M et al (2021) Dopamine in Parkinson’s disease. Clin Chim Acta 522:114–126.
  26. Levey AI, Hersch SM, Rye DB, Sunahara RK, Niznik HB, Kitt CA et al (1993) Localization of D1 and D2 dopamine receptors in brain with subtype-specifc antibodies. Proc Natl Acad Sci 90(19):8861–8865.
  27. Alexander GE (2022) Biology of Parkinson’s disease: pathogenesis and pathophysiology of a multisystem neurodegenerative disorder. Dialogues Clin Neurosci 6:259–280.
  28. Bertram L, Tanzi RE (2005) The genetic epidemiology of neurodegenerative disease. J Clin Investig 115(6):1449–1457.
  29. Cannon JR, Greenamyre JT (2011) The role of environmental exposures in neurodegeneration and neurodegenerative diseases. Toxicol Sci 124(2):225–250.
  30. C.A. Lane, J. Hardy, J.M. Schott, Alzheimer's disease, Eur. J. Neurol. 25 (1) (2018) 59e70.
  31. 38]. Zhang, P.F.; Xu, S.T.; Zhu, Z.Y.; Xu, J.Y. Multi-target design strategies for the improved treatment of Alzheimer’s disease. Eur. J.Med. Chem. 2019, 176, 228–247.
  32. 39. Rodriguez-Soacha, D.A.; Scheiner, M.; Decker, M. Multi-target-directed-ligands acting as enzyme inhibitors and receptor ligands. Eur. J. Med. Chem. 2019, 180, 690–706.
  33. 40. de Freitas Silva, M.; Pruccoli, L.; Morroni, F.; Sita, G.; Seghetti, F.; Viegas, C.; Tarozzi, A. The Keap1/Nrf2-ARE Pathway as a Pharmacological Target for Chalcones. Molecules 2018, 23, 1803. [CrossRef].
  34. 41.Ouyang, Y.; Li, J.; Chen, X.; Fu, X.; Sun, S.; Wu, Q. Chalcone Derivatives: Role in Anticancer Therapy. Biomolecules 2021, 11, 894. [CrossRef]
  35. 42. Jasim, H.A.; Nahar, L.; Jasim, M.A.; Moore, S.A.; Ritchie, K.J.; Sarker, S.D.; Uversky, N. Chalcones: Synthetic Chemistry Follows Where Nature Leads. Biomolecules 2021, 11, 1203. [CrossRef]
  36. 43. Thapa, P.; Upadhyay, S.P.; Suo, W.Z.; Singh, V.; Gurung, P.; Lee, E.S.; Sharma, R.; Sharma, M. Chalcone and Its Analogs: Therapeutic and Diagnostic Applications in Alzheimer’s Disease. Bioorg. Chem. 2021, 108, 104681.
  37. 44. Singh, P.; Anand, A.; Kumar, V. Recent Developments in Biological Activities of Chalcones: A Mini Review. Eur. J. Med. Chem. 2014, 85, 758–777.
  38. 45. Mathew, B.; Mathew, G.E.; Uçar, G.; Baysal, I.; Suresh, J.; Vilapurathu, J.K.; Prakasan, A.; Suresh, J.K.; Thomas, A. Development of Fluorinated Methoxylated Chalcones as Selective Monoamine Oxidase-B Inhibitors: Synthesis, Biochemistry and Molecular Docking Studies. Bioorg. Chem. 2015, 62, 22–29. [CrossRef] [PubMed]
  39. 46. Albuquerque, H.; Santos, C.; Cavaleiro, J.; Silva, A. Chalcones as Versatile Synthons for the Synthesis of 5- and 6-Membered Nitrogen Heterocycles. Curr. Org. Chem. 2014, 18, 2750–2775. [CrossRef]
  40. 47. Yamali, C., Engin, F.S., Bilginer, S., Tugrak, M., Ozmen Ozgun, D., Ozli, G., Levent, S., Saglik, B.N., Ozkay, Y. and Gul, H.I., 2021. Phenothiazine‐based chalcones as potential dual‐target inhibitors toward cholinesterases (AChE, BuChE) and monoamine oxidases (MAO‐A, MAO‐B). Journal of Heterocyclic Chemistry, 58(1), pp.161-171.
  41. 48. Wang, X.Q., Zhou, L.Y., Tan, R.X., Liang, G.P., Fang, S.X., Li, W., Xie, M., Wen, Y.H., Wu, J.Q. and Chen, Y.P., 2021. Design, Synthesis, and Evaluation of Chalcone Derivatives as Multifunctional Agents against Alzheimer's Disease. Chemistry & Biodiversity, 18(11), p.e2100341.
  42. 49. Sang, Z., Song, Q., Cao, Z., Deng, Y. and Zhang, L., 2022. Design, synthesis, and evaluation of chalcone-Vitamin E-donepezil hybrids as multi-target-directed ligands for the treatment of Alzheimer’s disease. Journal of Enzyme Inhibition and Medicinal Chemistry, 37(1), pp.69-85.
  43. 50. Tian, C., Qiang, X., Song, Q., Cao, Z., Ye, C., He, Y., Deng, Y. and Zhang, L., 2020. Flurbiprofen-chalcone hybrid Mannich base derivatives as balanced multifunctional agents against Alzheimer’s disease: Design, synthesis and biological evaluation. Bioorganic chemistry, 94, p.103477.
  44. 51. Kumar, S., Oh, J.M., Abdelgawad, M.A., Abourehab, M.A., Tengli, A.K., Singh, A.K., Ahmad, I., Patel, H., Mathew, B. and Kim, H., 2023. Development of isopropyl-tailed chalcones as a new class of selective MAO-B inhibitors for the treatment of Parkinson’s disorder. ACS omega, 8(7), pp.6908-6917.
  45. 52. Mathew, B., Baek, S.C., Thomas Parambi, D.G., Lee, J.P., Mathew, G.E., Jayanthi, S., Vinod, D., Rapheal, C., Devikrishna, V., Kondarath, S.S. and Uddin, M.S., 2019. Potent and highly selective dual‐targeting monoamine oxidase‐B inhibitors: Fluorinated chalcones of morpholine versus imidazole. Archiv der Pharmazie, 352(4), p.1800309.
  46. 53. Mellado, M., Salas, C.O., Uriarte, E., Viña, D., Jara‐Gutiérrez, C., Matos, M.J. and Cuellar, M., 2019. Design, synthesis and docking calculations of prenylated chalcones as selective monoamine oxidase B inhibitors with antioxidant activity. ChemistrySelect, 4(26), pp.7698-7703.
  47. 54. Oh, J.M., Baek, S.C., Lee, J.P., Tondo, A.R., Nicolotti, O., Kim, H. and Mathew, B., 2019. Design, synthesis and biological evaluation of oxygenated chalcones as potent and selective MAO-B inhibitors. Bioorganic Chemistry, 93, p.103335.
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