Abstract
Alzheimer’s disease (AD) is a complex neurological disorder characterised by decrease level of ACh and increased AChE expression. Inhibition of AChE is one of the common strategies to treat AD as it leads to increase Ach level quantitatively at the synaptic cleft. Acetylcholinesterase inhibitors (AChEIs) are used to treat various neurodegenerative disorders, and many are FDA approved for the management and cure of AD. AChEIs produce long term symptomatic effect, that contribute in other pathological mechanisms of the disease (e.g. formation of amyloid–β plaques) and have provided a rationale to the discovery of this class of inhibitors. Currently prescribed AChE inhibitors are Galantamine (natural alkaloid) and Rivastigmine (synthetic alkaloid compound) and have been considered beneficial for the treatment of mild to moderate AD. However, there is a need for the discovery of more effective compounds derived from natural sources as well as form synthetic sources as potential AChEIs. Findings and advances about natural and synthetic derivatives as potential sources of AChEIs will be collectively summarised in this review paper.
Keywords: Acetylcholineserase, AChE inhibitors, Alzheimer’s disease, Molecular modelling studies, Types of AChE inhibitors, drug discovery.
Graphical Abstract
[1]
Martorana, A.; Esposito, Z.; Koch, G. Beyond the cholinergic hypothesis: do current drugs work in Alzheimer’s disease? CNS Neursci. Ther., 2010, 16, 235-245.
[2]
Querfurth, H.W.; Selkoe, D.J. Calcium ionophore increases amyloid beta peptide production by cultured cells. Biochemistry, 1994, 33, 4550-4561.
[4]
Carson, K.A.; Geula, C.; Mesulam, M.M. Electron microscopic localization of cholinesterase activity in Alzheimer brain tissue. Brain Res., 1991, 540, 204-208.
[5]
Boyle, N.M.; Banck, M.; James, C.A.; Morley, C.; Vandermeersch, T.; Hutchison, G.R. Open Babel: An open chemical toolbox. J. Cheminf., 2011, 3, 332-345.
[6]
Hardy, J.; Selkoe, D.J. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science, 2002, 297, 353-356.
[7]
Selkoe, D.J.; Schenk, D. Alzheimer’s disease: Molecular understanding predicts amyloid-based therapeutics. Annu. Rev. Pharmacol. Toxicol., 2003, 43, 545-584.
[8]
Elina, Z.; James, A.R.N.; Raj, K.; Clive, H. Inflammation in Alzheimer’s disease: Relevance to pathogenesis and therapy. Delphine Boche Alzheimers Res. Ther., 2010, 2(1), 1.
[9]
Iranshahi, M.; Iranshahy, M. Traditional uses, phytochemistry and pharmacology of asafoetida (Ferula assa-foetida oleo-gum-resin)—A review. Ethnopharmacology, 2011, 134, 1-10.
[10]
Zhou, X.; Wang, X.B.; Wang, T.; Kong, L.Y. Design, synthesis, and acetylcholinesterase inhibitory activity of novel coumarin analogues. Bioorg. Med. Chem., 2008, 16, 8011-8021.
[11]
Sugimoto, H.; Yamanishi, Y.; Iimura, Y.; Kawakami, Y. Donepezil hydrochloride (E2020) and other acetylcholinesterase inhibitors. Curr. Med. Chem., 2000, 7, 303-339.
[12]
Kavanagh, S.; Gaudig, M.; Van, M.M.; Adami, M.; Delgado, A.; Guzman, C.; Jedenius, E.; Schäuble, B. Galantamine and behavior in Alzheimer disease: analysis of four trials. Acta Neurol. Scand., 2001, 124, 302-308.
[13]
Hoerr, R.; Noeldner, M.; Ensaculin, M. (KA-672 HCl): A multitransmitter approach to dementia treatment. CNS Drug Rev., 2002, 8, 143-158.
[14]
Alipour, M.; Khoobi, M.; Foroumadi, A.; Nadri, H.; Moradi, A.; Sakhteman, M.; Ghandi, M.; Shafiee, A. Novel coumarin derivatives bearing N-benzyl pyridinium moiety: potent and dual binding site acetylcholinesterase inhibitors. Bioorg. Med. Chem., 2012, 20, 7214-7222.
[16]
Carson, K.A.; Geula, C.; Mesulam, M.M. Electron microscopic localization of cholinesterase activity in Alzheimer brain tissue. Brain Res., 1991, 540, 204-208.
[17]
Koh, S.H.; Kim, S.H.; Kwon, H.; Park, Y.; Kim, K.S.; Song, C.W.; Kim, J.; Kim, M.H.; Yu, H.J.; Henkel, J.S.; Jung, H.K. Epigallocatechin gallate protects nerve growth factor differentiated PC12 cells from oxidative-radical-stress-induced apoptosis through its effect on phosphoinositide 3-kinase/Akt and glycogen synthase kinase-3. Brain Res. Mol. Brain Res., 2003, 118, 72-81.
[18]
Dan, C.; Ya-fei, P.; Chuan-Jun, L.; Yun-feng, X.; Yu-ren, J. Virtual screening of acetylcholinesterase inhibitors, In: M. Taha, Ed, Virtual Screening, InTech; Publisher, Shanghi,, 2012; pp. 83-90.
[19]
Enz, A.; Amstutz, R.; Boddeke, H.; Gemelin, G.; Malanowaski, J. Brain selective inhibition of acetylcholinesterase: a novel approach to therapy for Alzheimer’s disease. Prog. Brain Res., 1993, 98, 431-438.
[20]
Cardozo, M.G.; Kawai, Y.; Limura, Y.; Sugimoto, H.; Yaminishi, Y.; Hopefinger, A.J. Conformational analysis and molecular- shape comparisons of a series of indanone- benzylpiperidine inhibitors of acetylcholinesterase. J. Med. Chem., 1992, 35, 582-587.
[21]
Katzman, R.; Bick, K. The cholinergic story: hope for the patient and family, İn: Alzheimer’s Disease, the Changing View, first ed; Academic Press: London, 2000, p. 182. (Chapter 5).
[22]
Massoulié, J.; Bon, S. The molecular forms of cholinesterase and acetylcholinesterase in vertebrates. Annu. Rev. Neurosci., 1982, 5, 57-106.
[23]
Greig, N.H.; Utsukd, T.; Yu, X.; Zhu, H.W.; Holloway, T.; Perry, B.L.; Lehri, D.K.; Ingram, D.K. A new therapeutic target in the Alzheimer’s disease treatment: attention to butrylcholinesterase. Curr. Med. Res. Opin., 2001, 17, 159-165.
[24]
Johnson, G.; Moore, M.S. Peripheral anionic site of acetylcholinesterase: structure, functions and potential role in rational drug design. Curr. Pharm. Des., 2006, 12, 217-225.
[25]
Cavalli, A.; Bolognesi, M.L.; Minarini, A. Multi-targate-directed ligands to combat neurodegenerative disease. J. Med. Chem., 2008, 51(3), 347-372.
[26]
Quinn, D.M. Acetylcholinesterase: enzyme structure, reaction dynamics, and virtual transition states. Chem. Rev., 1987, 87, 955-979.
[27]
Pohanka, M. Cholinesterases, a target of pharmacology and toxicology. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub., 2011, 155, 219-230.
[28]
Taylor, P.; Lappi, S. Interaction of fluorescence probes with acetylcholinesterase. The site and specificity of propidium binding. Biochemistry, 1975, 14, 1989-1997.
[29]
Massoulié, J.; Bon, S. The molecular forms of cholinesterase and acetylcholinesterase in vertebrates. Annu. Rev. Neurosci., 1982, 5, 57-106.
[30]
Green, K.N.; LaFerla, F.M. Linking calcium to Ab and Alzheimer’s disease. Neuron, 2008, 59, 190-194.
[31]
Singh, M.; Kaur, M.; Kukreja, H.; Chugh, R.; Silakari, O.; Singh, D. Acetylcholinesterase inhibitors as Alzheimer therapy: from nerve toxins to neuroprotection. Eur. J. Med. Chem., 2013, 70, 165-188.
[32]
Arce, P.M.; Franco, R.I.M.; Munoz, G.C.G.; Perez, C.; Lopez, B.; Villaroya, M.; Lopez, G.M.; Garcia, G.A. Neuroprotective and cholinergic properties of multifunctional glutamic acid derivatives for the treatment of Alzheimer’s disease. J. Med. Chem., 2009, 22, 7249-7257.
[33]
Glenner, G.G.; Wong, C.W. Alzheimer’s disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun., 1984, 120, 885-890.
[34]
Selkoe, D.J.; Podlisny, M.B.; Annu, R.; Genomics, H.G. Synthesis and evaluation of 4-substituted coumarins as novel acetylcholinesterase inhibitors. Eur. J. Med. Chem., 2002, 99, 251.
[35]
Alipour, M.; Khoobi, M.; Foroumadi, A.; Nadri, H.; Moradi, A.; Sakhteman, M.; Ghandi, M.; Shafiee, A. Novel coumarin derivatives bearing N-benzyl pyridinium moiety: Potent and dual binding site acetylcholinesterase inhibitors. Bioorg. Med. Chem., 2012, 20, 7214-7222.
[36]
Goedert, M.; Spillantini, M.G.; Crowther, R.A. Tau proteins and neurofibrillary degeneration. Brain Pathol., 1991, 1, 279-286.
[37]
Iqbal, K.; Alonso, A.C.; Chen, S.; Chohan, M.O.; El-Akkad, E.; Gong, C.X.; Khatoon, S.; Li, B.; Liu, F.; Rahman, A.; Tanimukai, H.; Grundke-Iqbal, I. Tau pathology in Alzheimer disease and other tauopathies. Biochim. Biophys. Acta, 2005, 1739, 198-210.
[38]
Chun, W.; Johnson, G.V. The role of tau phosphorylation and cleavage in neuronal cell death. Front. Biosci., 2007, 12, 733-756.
[39]
Pierrot, N.; Santos, S.F.; Feyt, C.; Morel, M.; Brion, J.P.; Octave, J.N. Calcium mediated transient phosphorylation of tau and amyloid precursor protein followed by intraneuronal amyloid-beta accumulation. J. Biol. Chem., 2006, 281, 39907-39914.
[40]
Bojarski, L.; Herms, J.; Kuznicki, J. Calcium dysregulation in Alzheimer’s disease. Neurochem. Int., 2008, 52, 621-633.
[41]
Wang, Y.; Yang, Y.; Tian, J.; Liu, J.P. Huperzine A for alzheimer’s disease: a systematic review and meta-analysis of randomized clinical trials. PLoS One, 2013, 8(9), e74916.
[42]
Edlund, C.; Söderberg, M.; Kristensson, K. Isoprenoids in aging and neurodegeneration. Neurochem. Int., 1994, 25, 35-38.
[43]
Ibrahim, M.; Farooq, T.; Hussain, N.; Hussain, A.; Gulzar, T.; Hussain, I.; Akash, H.S.M.; Fouzia, S.R. Acetyl and butyryl cholinesterase inhibitory sesquiterpene lactones from Amberboa ramose. Chem. Central. J., 2013, 7, 116.
[44]
Murray, A.P.; Faraoni, M.B.; Castro, M.J.; Alza, N.P.; Cavallaro, V. Natural AChE ınhibitors from plants and their contribution to alzheimer’s disease therapy. Curr. Neuropharmacol., 2013, 11(4), 388-413.
[45]
Jain, M.P.; Sharma, V.K. Phytochemical investigation of roots of Adhatoda Vasica. Plant Medica., 1982, 46, 250.
[47]
Murray, A.P.; Faraoni, M.B.; Castro, M.J.; Alza, N.P.; Cavallaro, V. Natural AChE ınhibitors from plants and their contribution to alzheimer’s disease therapy. Curr. Neuropharmacol., 2013, 11, 388-413.
[48]
Wang, B.S.; Wang, H.; Wie, Z.H.; Song, Y.Y.; Zhang, L.; Chen, H.Z. Efficacy and safety of natural acetylcholinesterase inhibitors huperzine A in the treatment of Alzheimer’s disease: An updated meta-analysis. J. Neural Transmission., 2009, 116, 457-465.
[49]
Catto, M.; Pisani, L.; Leonetti, F.; Nicolotti, O.; Pesce, P.; Stefanachi, A.; Cellamare, S.; Carotti, A. Design, synthesis and biological evaluation of coumarin alkylamines as potent and selective dual binding site inhibitors of acetylcholinesterase. Bioorg. Med. Chem., 2013, 21, 146-152.
[50]
Van der zee, E.A.; Platt, B.; Riedel, G. Acetylcholine: future research and perspectives. Behav. Brain Res., 2011, 221, 583-587.
[51]
Meng, F.; Mao, F.; Shan, W.; Qin, R. Huang, l.; Li, X. Design, synthesis, and evaluation of indanone derivatives as acetylcholinesterase inhibitors and metal-chelating agents. Bioorg. Med. Chem., 2012, 22, 4462-4466.
[52]
Zangara, A. The psychopharmacology of huperzine A: An alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer’s disease. Pharmacol. Biochem. Behav., 2013, 75, 675-686.
[53]
Khanaposhtani, M.M.; Saeedi, M.; Zafarghandi, S.N.; Mahdavi, M.; Sabourian, R.; Razkenari, K.E. Potent acetylcholinesterase inhibitors: Design, synthesis, biological evaluation, and docking study of acridone linked to 1,2,3-triazole derivatives. Eur. J. Med. Chem., 2015, 92, 799-806.
[54]
Khoobi, M.; Alipour, M.; Sakhyeman, A.; Nadri, H.; Moradi, A.; Ghandi, M.; Emami, S.; Foroumadi, A. Design, synthesis, biological evaluation and docking study of 5-oxo- 4,5-dihydropyrano[3,2-c]chromene derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors. Eur. J. Med. Chem., 2013, 68, 260-269.
[55]
Cummings, J.L.; Askin-Edger, S. Design, synthesis and evaluation of novel heterodimers of donepezil and huperzine fragments as acetylcholinesterase inhibitors. Bioorg. Med. Chem., 2000, 13, 385.
[56]
Zhu, J.; Wu, F.C.; Li, X.; Wu, S.G. Synthesis, biological evaluation and molecular modelling of substituted 2-aminobenzimidazoles as novel inhibitors of acetylcholinesterase and butyrylcholinesterase. Bioorg. Med. Chem., 2013, 21, 4218-4224.
[57]
Leonetti, F.; Catto, M.; Nicolotti, O.; Pisani, L.; Cappa, A.; Stefanachi, A.; Carotti, A. Homo- and hetero-bivalent edrophonium-like ammonium salts as highly potent, dual binding site AChE inhibitors. Bioorg. Med. Chem., 2008, 16, 7450-7456.
[58]
Chen, Y.; Fang, L.; Peng, S.; Liao, H.; Lehmann, J. Discovery of a novel acetylcholinesterase inhibitor by structural- based virtual screening techniques. Bioorg. Med. Chem. Lett., 2012, 22, 3181.
[59]
Khoobi, M.; Alipour, M.; Sakhyeman, A.; Nadri, H.; Moradi, A.; Ghandi, M.; Emami, S.; Foroumadi, A. Design, synthesis, biological evaluation and docking study of 5-oxo- 4,5-dihydropyrano[3,2-c]chromene derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors. Eur. J. Med. Chem., 2013, 68, 260-269.
[60]
Liu, S.; Shang, R.; Shi, L.; Wan, C.C.D.; Lin, H. Synthesis and biological evaluation of 7 H-thiazolo [3, 2-b]-1, 2, 4- triazin-7-one derivatives as dual binding site acetylcholinesterase inhibitors. Eur. J. Med. Chem., 2014, 81, 237.
[61]
Bukhari, A.N.S.; Ser, M.; Hassan, M.; Masand, H.V.; Mahajan, T.D.; Amjad, W.M. Synthesis of α, β-unsaturated carbonyl based compounds as acetylcholinesterase and butyrylcholinesterase inhibitors: Characterization, molecular modeling, QSAR studies and effect against amyloid β-induced cytotoxicity. Eur. J. Med. Chem., 2014, 83, 355-365.
Related Books
Oxygen: High Enzymatic Reactivity of Reactive Oxygen Species
Article Metrics
95
7
1