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Central Nervous System Agents in Medicinal Chemistry

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ISSN (Print): 1871-5249
ISSN (Online): 1875-6166

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Research Article

Exploring the Therapeutic Potential of Alkaloids in Alzheimer's Disease Management

Author(s): Randhir Singh, Nidhi Rani*, Rajwinder Kaur, Geeta Chahal, Praveen Kumar and Gagandeep Kaur

Volume 24, Issue 2, 2024

Published on: 11 January, 2024

Page: [206 - 218] Pages: 13

DOI: 10.2174/0118715249269092231109181638

Price: $65

Abstract

Background: Alkaloids are important phytoconstituents obtained from various plant sources. The study's primary goal is to assess the anti-Alzheimer potential of alkaloids using a molecular docking study. Alzheimer's disease (AD) is considered a gradual decline in memory, reasoning, decision-making, orientation to one's physical surroundings, and language.

Materials and Methods: The main target i.e. acetylcholinesterase proteins was selected for the molecular docking study.

Results: The structures of various alkaloids were drawn using Chem Draw Software, PDB was retrieved from the RCSB PDB database, and molecular docking study was performed on Molergo Virtual Docker. The potential alkaloids were identified with anti-Alzheimer potency.

Conclusion: Reserpine, vinblastine, ergotamine, and tubocurarine were found to exhibit potential anti-Alzheimer potency.

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[1]
Alzheimer’s Disease Facts and figures. Rep; Alzheimer’s Association: Chicago, 2010, Vol. 6, p. 2.
[2]
2010 Alzheimer’s disease facts and figures. Alzheimers Dement., 2010, 6(2), 158-194.
[3]
Jiang, T.; Yu, J.T.; Tian, Y.; Tan, L. Epidemiology and etiology of Alzheimer’s disease: From genetic to non-genetic factors. Curr. Alzheimer Res., 2013, 10(8), 852-867.
[http://dx.doi.org/10.2174/15672050113109990155] [PMID: 23919770]
[4]
Jiang, T.; Yu, J.T.; Tan, L. Novel disease-modifying therapies for Alzheimer’s disease. J. Alzheimers Dis., 2012, 31(3), 475-492.
[http://dx.doi.org/10.3233/JAD-2012-120640] [PMID: 22669013]
[5]
(a) Jiang, Teng; Chuen-Chung, R.C.; Hanna, R.; Jin-Tai, Y. Advances in Alzheimer’s Disease: From bench to bedside. BioMed Res. Int., 2015, 1015.;
(b) Sharma, V.K.; Singh, T.G.; Garg, N. Dysbiosis and alzheimers disease: A role for chronic stress? Biomolecules, 2021, 11, 678.
[http://dx.doi.org/10.1155/2015/202676]
[6]
Alzheimer’s Association Report. “Alzheimer’s disease facts and figures Alzheimer’s Association. Alzheimers Dement., 2015, 11, 332-384.
[7]
Zou, Z.; Liu, C.; Che, C.; Huang, H. Clinical genetics of Alzheimer’s Disease. BioMed Res. Int., 2014, 2014, 291862.
[http://dx.doi.org/10.1155/2014/291862]
[8]
Povova, J.; Ambroz, P.; Bar, M.; Pavukova, V.; Sery, O.; Tomaskova, H.; Janout, V. Epidemiological of and risk factors for Alzheimer’s disease: A review. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub., 2012, 156(2), 108-114.
[http://dx.doi.org/10.5507/bp.2012.055] [PMID: 22837131]
[9]
Blennow, K.; de Leon, M.J.; Zetterberg, H. Alzheimer’s disease. Lancet, 2006, 368(9533), 387-403.
[http://dx.doi.org/10.1016/S0140-6736(06)69113-7] [PMID: 16876668]
[10]
Yiannopoulou, K.G.; Papageorgiou, S.G. Current and future treatments for Alzheimer’s disease. Ther. Adv. Neurol. Disord., 2013, 6(1), 19-33.
[http://dx.doi.org/10.1177/1756285612461679] [PMID: 23277790]
[11]
Bhushan, I.; Kour, M.; Kour, G.; Gupta, S.; Sharma, S.; Yadav, A. Alzheimer’s disease: Causes & treatment – A review. Annals of Biotechnology, 2018, 1(1), 1002.
[http://dx.doi.org/10.33582/2637-4927/1002]
[12]
Almkvist, O. Neuropsychological features of early Alzheimer’s disease: preclinical and clinical stages. Acta Neurol. Scand., 1996, 94(S165), 63-71.
[http://dx.doi.org/10.1111/j.1600-0404.1996.tb05874.x] [PMID: 8740991]
[13]
Förstl, H.; Kurz, A. Clinical features of Alzheimer’s disease. Eur. Arch. Psychiatry Clin. Neurosci., 1999, 249(6), 288-290.
[http://dx.doi.org/10.1007/s004060050101] [PMID: 10653284]
[14]
Chou, E. Alzheimer’s Disease: Current and Future Treatments. A Review. International Journal of Medical Students, 2014, 2(2), 56-63.
[http://dx.doi.org/10.5195/ijms.2014.85]
[15]
Galasko, D. An integrated approach to the management of Alzheimer’s disease: assessing cognition, function and behaviour. Eur. J. Neurol., 1998, 5(S4), S9-S17.
[http://dx.doi.org/10.1111/j.1468-1331.1998.tb00444.x]
[16]
Burns, A. Psychiatric phenomena in dementia of the Alzheimer type. Int. Psychogeriatr., 1992, 4(3), 43-54.
[http://dx.doi.org/10.1017/S1041610292001145] [PMID: 1504286]
[17]
Acetylcholinesterase in Alzheimer’s disease. Mechanisms of Ageing and Development. Volume 122, Issue 16, November 2001, Pages 1961-1969. B) Sharma, V.K.; Singh, T.G.; Singh, S.; Garg, N.; Dhiman, S. Apoptotic Pathways and Alzehimers Disease: Probing Therapeutic Potential. Neurochem. Res., 2021, 46, 3103-3122.
[18]
Thies, W.; Bleiler, L. 2013 Alzheimer’s disease facts and figures. Alzheimers Dement., 2013, 9(2), 208-245.
[http://dx.doi.org/10.1016/j.jalz.2013.02.003] [PMID: 23507120]
[19]
Francis, P.T.; Palmer, A.M.; Snape, M.; Wilcock, G.K. The cholinergic hypothesis of Alzheimer’s disease: a review of progress. J. Neurol. Neurosurg. Psychiatry, 1999, 66(2), 137-147.
[http://dx.doi.org/10.1136/jnnp.66.2.137] [PMID: 10071091]
[20]
Corbett, A.; Williams, G.; Ballard, C. Drug repositioning: an opportunity to develop novel treatments for Alzheimer’s disease. Pharmaceuticals (Basel), 2013, 6(10), 1304-1321.
[http://dx.doi.org/10.3390/ph6101304] [PMID: 24275851]
[21]
Hsiao, K.; Chapman, P.; Nilsen, S.; Eckman, C.; Harigaya, Y.; Younkin, S.; Yang, F.; Cole, G. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science, 1996, 274(5284), 99-103.
[http://dx.doi.org/10.1126/science.274.5284.99] [PMID: 8810256]
[22]
Lacor, P.N.; Buniel, M.C.; Furlow, P.W.; Sanz Clemente, A.; Velasco, P.T.; Wood, M.; Viola, K.L.; Klein, W.L. Abeta oligomer-induced aberrations in synapse composition, shape, and density provide a molecular basis for loss of connectivity in Alzheimer’s disease. J. Neurosci., 2007, 27(4), 796-807.
[http://dx.doi.org/10.1523/JNEUROSCI.3501-06.2007] [PMID: 17251419]
[23]
Lambert, M.P.; Barlow, A.K.; Chromy, B.A.; Edwards, C.; Freed, R.; Liosatos, M.; Morgan, T.E.; Rozovsky, I.; Trommer, B.; Viola, K.L.; Wals, P.; Zhang, C.; Finch, C.E.; Krafft, G.A.; Klein, W.L. Diffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins. Proc. Natl. Acad. Sci. USA, 1998, 95(11), 6448-6453.
[http://dx.doi.org/10.1073/pnas.95.11.6448] [PMID: 9600986]
[24]
Mudher, A.; Lovestone, S. Alzheimer’s disease – do tauists and baptists finally shake hands? Trends Neurosci., 2002, 25(1), 22-26.
[http://dx.doi.org/10.1016/S0166-2236(00)02031-2] [PMID: 11801334]
[25]
Trojanowski, J.Q.; Lee, V.M.Y. Rous-Whipple Award Lecture. The Alzheimer’s brain: finding out what’s broken tells us how to fix it. Am. J. Pathol., 2005, 167(5), 1183-1188.
[http://dx.doi.org/10.1016/S0002-9440(10)61206-0] [PMID: 16251403]
[26]
Sireesha, B.; Reddy, B.V.; Basha, S.K.; Chandra, K.; Anasuya, D.; Bhavani, M. A Review on Pharmacological Activities of Alkaloids. World Journal of Current Medical and Pharmaceutical Research, 2019, 1(6), 230-234.
[http://dx.doi.org/10.37022/WJCMPR.2019.01068]
[27]
Stadtman, E.R.; Moskovitz, J.; Levine, R.L. Oxidation of methionine residues of proteins: Bqiological consequences. Antioxid. Redox Signal., 2003, 5(5), 577-582.
[http://dx.doi.org/10.5772/intechopen.85400]
[28]
Roy.; A. A Review on the Alkaloids an Important Therapeutic Compound from Plants. International Journal of Plant Biotechnology, 2017, 3(2), 1-9.
[29]
Debnath, B.; Singh, W.S.; Das, M.; Goswami, S.; Singh, M.K.; Maiti, D.; Manna, K. Role of plant alkaloids on human health: A review of biological activities. Mater. Today Chem., 2018, 9, 56-72.
[http://dx.doi.org/10.1016/j.mtchem.2018.05.001]
[30]
Ng, Y.P.; Or, T.C.T.; Ip, N.Y.; Ip, N.Y. Plant alkaloids as drug leads for Alzheimer’s disease. Neurochem. Int., 2015, 89, 260-270.
[http://dx.doi.org/10.1016/j.neuint.2015.07.018] [PMID: 26220901]
[31]
Naaz, H.; Singh, S.; Pandey, V.P.; Singh, P.; Dwivedi, U.N. Anti-cholinergic alkaloids as potential therapeutic agents for Alzheimer’s disease: an in silico approach. Indian J. Biochem. Biophys., 2013, 50(2), 120-125.
[PMID: 23720886]
[32]
Ji, H.F.; Shen, L. Berberine: a potential multipotent natural product to combat Alzheimer’s disease. Molecules, 2011, 16(8), 6732-6740.
[http://dx.doi.org/10.3390/molecules16086732] [PMID: 21829148]
[33]
Zhang, J.; Chen, L.; Sun, J. Oxoisoaporphine alkaloids: Prospective anti-alzheimer’s disease, anticancer, and antidepressant agents. ChemMedChem, 2018, 13(13), 1262-1274.
[http://dx.doi.org/10.1002/cmdc.201800196]
[34]
Laid, M. Antidiabetic, anti-alzheimer and antioxidant activities of alkaloids extract of pergularia tomentosa l. Collected from algerian sahara. Int. J. Sci. Res., 2020, 76, 2/1.
[http://dx.doi.org/10.21506/j.ponte.2020.2.13]
[35]
Khan, S.; Khan, H.U.; Khan, F.A.; Shah, A.; Wadood, A.; Ahmad, S.; Almehmadi, M.; Alsaiari, A.A.; Shah, F.U.; Kamran, N. Anti-Alzheimer and Antioxidant Effects of Nelumbo nucifera L. Alkaloids, Nuciferine and Norcoclaurine in Alloxan-Induced Diabetic Albino Rats. Pharmaceuticals (Basel), 2022, 15(10), 1205.
[http://dx.doi.org/10.3390/ph15101205] [PMID: 36297317]
[36]
Rani, N.; Singh, R.; Kumar, P. Molecular Modeling Study for the Evaluation of Natural Compounds as Potential Lanosterol 14α-Demethylase Inhibitors. Lett. Drug Des. Discov., 2022, 19(5), 459-471.
[http://dx.doi.org/10.2174/1570180818666211027114007]
[37]
Rani, N.; Kumar, P.; Singh, R.; Sharma, A. Molecular docking evaluation of imidazole analogues as potent candida albicans 14α-Demethylase inhibitors. Curr. Computeraided Drug Des., 2015, 11(1), 8-20.
[http://dx.doi.org/10.2174/1573409911666150617113645] [PMID: 26081558]
[38]
Rani, N.; Kumar, P.; Singh, R. Molecular modeling studies of halogenated imidazoles against 14 alpha-demethylase from Candida albicans for treating fungal infections. Infect. Disord. Drug Targets, 2020, 20(2), 208-222.
[39]
Rani, N.; Kumar, P.; Singh, R. Molecular modeling study of fluoro substituted imidazole derivatives as 14α- demethylase inhibitors. Int. J. Drug Deliv. Technol., 2017, 7(7), 297-317.
[40]
Ferreira, L.; dos Santos, R.; Oliva, G.; Andricopulo, A. Molecular docking and structure-based drug design strategies. Molecules, 2015, 20(7), 13384-13421.
[http://dx.doi.org/10.3390/molecules200713384] [PMID: 26205061]
[41]
Rani, N.; Kumar, P.; Singh, R.; de Sousa, D.P.; Sharma, P. Current and future prospective of a versatile moiety. Imidazole. Curr. Drug Targets, 2020, 21(11), 1130-1155.
[http://dx.doi.org/10.2174/1389450121666200530203247] [PMID: 32472996]
[42]
Rani, N.; Singh, R. Design, synthesis, antimicrobial evaluation and molecular modeling study of new 2-mercaptoimidazoles (series-iii). Lett. Drug Des. Discov., 2019, 16(5), 512-521.
[http://dx.doi.org/10.2174/1570180815666181015144431]
[43]
Thomsen, R.; Christensen, M.H. MolDock: A new technique for high-accuracy molecular docking. J. Med. Chem., 2006, 49(11), 3315-3321.
[http://dx.doi.org/10.1021/jm051197e] [PMID: 16722650]

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