Substituted Aminobenzothiazole Derivatives of Tacrine: Synthesis and Study on Learning and Memory Impairment in Scopolamine-Induced Model of Amnesia in Rat

Author(s): Abbas Ahmadi*, Mehrdad Roghani, Sanaz Noori, Babak Nahri-Niknafs.

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 19 , Issue 1 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Currently, there is no conclusive cure for Alzheimer’s disease (AD) and existing treatments mainly offer symptomatic relief. Dysfunction of the cholinergic system plays an important role in the pathogenesis of AD. Tacrine (1, 2, 3, 4-tetrahydroacridin-9-amine, III) was the first approved agent for the palliative therapy of AD but its use is associated with some complications. Development of novel multi target derivatives of Tacrine with lower complications is strongly warranted. In this study, new aminobenzothiazole (1-5, with many useful biological and pharmacological properties) analogues (IV-VIII) were synthesized by changing of amine moiety of III. Then, the effects of these new compounds on learning and memory impairment in scopolamine-induced model of amnesia were studied and the outcomes were compared with control and Tacrine groups in rat.

Material and Methods: The rats received Tacrine or its derivatives (IV-VIII) i.p. for two weeks at a dose of 10 mg/kg. For induction of amnesia, scopolamine at a dose of 1 mg/kg was daily administered i.p. started on day-8 till the end of the study. Behavioral experiments including Y-maze, novel object recognition (discrimination) and passive avoidance paradigms were conducted at week 2.

Results: Data analysis showed that some Tacrine derivatives, especially VII with 2-amino, 6-nitrobenzothiazole moiety, could markedly and significantly improve alternation score, discrimination ratio and step through latency compared to control and Tacrine groups.

Conclusion: These findings indicated that some of these derivatives (especially compounds VI and VII) are capable to mitigate learning and memory deficits in scopolamine-induced model of amnesia in rats and may have potential benefit in management of patients with AD.

Keywords: Tacrine derivatives, scopolamine, amnesia, Alzheimer’s disease, learning and memory deficits, Y-maze.

[1]
Newman, M.; Musgrave, I.F.; Lardelli, M. Alzheimer disease: Amyloidogenesis, the presenilins and animal models. Biochimica et Biophysica Acta, 2007, 1772(3), 285-297.
[2]
Amemori, T.; Jendelova, P.; Ruzicka, J.; Urdzikova, L.M.; Sykova, E. Alzheimer’s disease: Mechanism and approach to cell therapy. Int. J. Mol. Sci., 2015, 16(11), 26417-26451.
[3]
Simic, G.; Babic-Leko, M.; Wray, S.; Harrington, C.; Delalle, I.; Jovanov-Milosevic, N. Tau Protein Hyperphosphorylation and Aggregation in Alzheimer’s Disease and Other Tauopathies, and Possible Neuroprotective Strategies. Biomolecules, 2016, 6(1), 6.
[4]
Ferreira, S.T.; Klein, W.L. The Abeta oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease. Neurobiol. Learn. Mem., 2011, 96(4), 529-543.
[5]
Klyubin, I.; Cullen, W.K.; Hu, N.W.; Rowan, M.J. Alzheimer’s disease Abeta assemblies mediating rapid disruption of synaptic plasticity and memory. Mol. Brain, 2012, 5, 25.
[6]
Ma, T.; Klann, E. Amyloid beta: Linking synaptic plasticity failure to memory disruption in Alzheimer’s disease. J. Neurochem., 2012, 120(Suppl. 1), 140-148.
[7]
Jakob-Roetne, R.; Jacobsen, H. Alzheimer’s disease: From pathology to therapeutic approaches. Angew. Chem. Int. Ed. In. Engl., 2009, 48(17), 3030-3059.
[8]
Mahley, R.W.; Huang, Y. Alzheimer disease: multiple causes, multiple effects of apolipoprotein E4, and multiple therapeutic approaches. Ann. Neurol., 2009, 65(6), 623-625.
[9]
Arendt, T.; Henning, D.; Gray, J.A.; Marchbanks, R. Loss of neurons in the rat basal forebrain cholinergic projection system after prolonged intake of ethanol. Brain Res. Bull., 1988, 21(4), 563-569.
[10]
Bartus, R.T.; Dean, R.L.; Beer, B.; Lippa, A.S. The cholinergic hypothesis of geriatric memory dysfunction. Science, 1982, 217(4558), 408-414.
[11]
Winblad, B.; Messamore, E.; O’Neill, C.; Cowburn, R. Biochemical pathology and treatment strategies in Alzheimer’s disease: Emphasis on the cholinergic system. Acta Neurol. Scand. Suppl., 1993, 149, 4-6.
[12]
Patel, S.; Tariot, P.N. Pharmacologic models of Alzheimer’s disease. Psychiatr. Clin. North Am., 1991, 14(2), 287-308.
[13]
Rupniak, N.M.; Steventon, M.J.; Field, M.J.; Jennings, C.A.; Iversen, S.D. Comparison of the effects of four cholinomimetic agents on cognition in primates following disruption by scopolamine or by lists of objects. Psychopharmacol, 1989, 99(2), 189-195.
[14]
Christensen, H.; Maltby, N.; Jorm, A.F.; Creasey, H.; Broe, G.A. Cholinergic ‘blockade’ as a model of the cognitive deficits in Alzheimer’s disease. Brain, 1992, 115(Pt 6), 1681-1699.
[15]
Klinkenberg, I.; Blokland, A. The validity of scopolamine as a pharmacological model for cognitive impairment: A review of animal behavioral studies. Neurosci. Biobehav. Rev., 2010, 34(8), 1307-1350.
[16]
Milelli, A.; De Simone, A.; Ticchi, N.; Chen, H.H.; Betari, N.; Andrisano, V. Tacrine-based multifunctional agents in alzheimer’s disease: An old story in continuous development. Curr. Med. Chem., 2017. doi: 10.2174/0929867324666170309123920. [Epub ahead of print]
[17]
Detrait, E.R.; Hanon, E.; Dardenne, B.; Lamberty, Y. The inhibitory avoidance test optimized for discovery of cognitive enhancers. Behav. Res. Methods, 2009, 41(3), 805-811.
[18]
Pan, S.Y.; Han, Y.F. Learning deficits induced by 4 belladonna alkaloids are preferentially attenuated by Tacrine. Acta Pharmacol. Sin., 2000, 21(2), 124-130.
[19]
Wu, W.Y.; Dai, Y.C.; Li, N.G.; Dong, Z.X.; Gu, T.; Shi, Z.H. Novel multitarget-directed Tacrine derivatives as potential candidates for the treatment of Alzheimer’s disease. J. Enzyme Inhib. Med. Chem., 2017, 32(1), 572-587.
[20]
Sameem, B.; Saeedi, M.; Mahdavi, M.; Shafiee, A. A review on Tacrine-based scaffolds as multi-target drugs (MTDLs) for Alzheimer’s disease. Eur. J. Med. Chem., 2017, 128, 332-345.
[21]
Malik, J.K.; Manvi, F.V.; Nanjwade, B.K.; Singh, S.; Purohit, P. Review of the 2-Amino substituted benzothiazoles: Different methods of the synthesis. Der Pharmacia Lettre, 2010, 2(1), 347-359.
[22]
Hiremathad, A.; Chand, K.; Raquel Esteves, A.; Cardoso, S.M.; Ramsay, R.R.; Chaves, S.; Keri, R.S.; Amélia Santos, M. Tacrine-allyl/propargylcysteine-benzothiazole trihybrids as potential anti-Alzheimer’s drug candidates. RSC Advances, 2016, 6, 53519-53532.
[23]
Carlier, P.R.; Fan Han, Y. Evaluation of Short-tether Bis-THA AChE inhibitors; A further test of the dual binding site hypothesis. Bioorg. Med. Chem., 1999, 7, 351-357.
[24]
Lee, T.B.K.; Goehring, K.E. Methods for the preparation of 9-amino-1,2,3,4-tetrahydroacridine. US Patent 5155226, 1992.
[25]
Nabeshima, T.; Maruyama, E.; Katoh, A.; Kameyama, T. The effect of Tacrine (THA) on cycloheximide- and basal forebrain lesion-induced memory deficit in rats. Jpn. J. Pharmacol., 1991, 57(3), 311-319.
[26]
Yoshida, S.; Suzuki, N. Antiamnesic and cholinomimetic side-effects of the cholinesterase inhibitors, physostigmine, Tacrine and NIK-247 in rats. Eur. J. Pharmacol., 1993, 250(1), 117-124.
[27]
Milic, M.; Timic, T.; Joksimovic, S.; Biawat, P.; Rallapalli, S.; Divljakovic, J. PWZ-029, an inverse agonist selective for alpha(5) GABAA receptors, improves object recognition, but not water-maze memory in normal and scopolamine-treated rats. Behav. Brain Res., 2013, 241, 206-213.
[28]
Malik, J.; Kaur, J.; Choudhary, S. Standardized extract of Lactuca sativa Linn. and its fractions abrogates scopolamine-induced amnesia in mice: A possible cholinergic and antioxidant mechanism. Nutr. Neurosci., 2017, 1-12.
[29]
Park, H.R.; Lee, H.; Park, H.; Cho, W.K.; Ma, J.Y. Fermented Sipjeondaebo-tang alleviates memory deficits and loss of hippocampal neurogenesis in scopolamine-induced amnesia in mice. Sci. Rep., 2016, 6, 22405.
[30]
Roghani, M.; Joghataie, M.T.; Jalili, M.R.; Baluchnejadmojarad, T. Time course of changes in passive avoidance and Y-maze performance in male diabetic rats. Iran. Biomed. J., 2006, 10(2), 99-104.
[31]
Nasri, S.; Roghani, M.; Baluchnejadmojarad, T.; Balvardi, M.; Rabani, T. Chronic cyanidin-3-glucoside administration improves short-term spatial recognition memory but not passive avoidance learning and memory in streptozotocin-diabetic rats. Phytother. Res., 2012, 26(8), 1205-1210.
[32]
Stuart, S.A.; Robertson, J.D.; Marrion, N.V.; Robinson, E.S. Chronic pravastatin but not atorvastatin treatment impairs cognitive function in two rodent models of learning and memory. PLoS One, 2013, 8(9), e75467.
[33]
Baluchnejadmojarad, T.; Kiasalari, Z.; Afshin-Majd, S.; Ghasemi, Z.; Roghani, M. S-allyl cysteine ameliorates cognitive deficits in streptozotocin-diabetic rats via suppression of oxidative stress, inflammation, and acetylcholinesterase. Eur. J. Pharmacol., 2017, 794, 69-76.
[34]
Kiasalari, Z.; Heydarifard, R.; Khalili, M.; Afshin-Majd, S.; Baluchnejadmojarad, T.; Zahedi, E. Ellagic acid ameliorates learning and memory deficits in a rat model of Alzheimer’s disease: An exploration of underlying mechanisms. Psychopharmacology (Berl.), 2017, 234(12), 1841-1852.
[35]
Zarezadeh, M.; Baluchnejadmojarad, T.; Kiasalari, Z.; Afshin-Majd, S.; Roghani, M. Garlic active constituent s-allyl cysteine protects against lipopolysaccharide-induced cognitive deficits in the rat: Possible involved mechanisms. Eur. J. Pharmacol., 2017, 795, 13-21.
[36]
Roghani, M.; Joghataie, M.T.; Jalali, M.R.; Baluchnejadmojarad, T. Time course of changes in passive avoidance and Y-maze performance in male diabetic rats. Iran. Biomed. J., 2006, 10(2), 99-104.
[37]
Ahshin-Majd, S.; Zamani, S.; Kiamari, T.; Kiasalari, Z.; Baluchnejadmojarad, T.; Roghani, M. Carnosine ameliorates cognitive deficits in streptozotocin-induced diabetic rats: Possible involved mechanisms. Peptides, 2016, 86, 102-111.
[38]
Ghofrani, S.; Joghataei, M.T.; Mohseni, S.; Baluchnejadmojarad, T.; Bagheri, M.; Khamse, S. Naringenin improves learning and memory in an Alzheimer’s disease rat model: Insights into the underlying mechanisms. Eur. J. Pharmacol., 2015, 764, 195-201.
[39]
Kiasalari, Z. Khalili, M.; Shafiee, S.; Roghani, M. The effect of Vitamin E on learning and memory deficits in intrahippocampal kainate-induced temporal lobe epilepsy in rats. Indian J. Pharmacol., 2016, 48(1), 11-14.
[40]
Mokhtari, Z.; Baluchnejadmojarad, T.; Nikbakht, F.; Mansouri, M.; Roghani, M. Riluzole ameliorates learning and memory deficits in Abeta25-35-induced rat model of Alzheimer’s disease and is independent of cholinoceptor activation. Biomed. Pharmacother., 2017, 87, 135-144.
[41]
Foyet, H.S.; Abaissou, H.H.; Wado, E.; Acha, E.A.; Alin, C. Emilia coccinae (SIMS) G Extract improves memory impairment, cholinergic dysfunction, and oxidative stress damage in scopolamine-treated rats. BMC Complement. Altern. Med., 2015, 15, 333.
[42]
Choi, Y.J.; Yang, H.S.; Jo, J.H.; Lee, S.C.; Park, T.Y.; Choi, B.S. Anti-Amnesic Effect of Fermented Ganoderma lucidum Water Extracts by Lactic Acid Bacteria on Scopolamine-Induced Memory Impairment in Rats. Prev. Nutr. Food Sci., 2015, 20(2), 126-132.
[43]
Ngoupaye, G.T.; Pahaye, D.B.; Ngondi, J.; Moto, F.C.O.; Bum, E.N. Gladiolus dalenii lyophilisate reverses scopolamine-induced amnesia and reduces oxidative stress in rat brain. Biomed. Pharmacother., 2017, 91, 350-357.
[44]
Xu, P.; Wang, K.; Lu, C.; Dong, L.; Gao, L.; Yan, M. Protective effect of lavender oil on scopolamine induced cognitive deficits in mice and H2O2 induced cytotoxicity in PC12 cells. J. Ethnopharmacol., 2016, 193, 408-415.
[45]
Lee, B.; Shim, I.; Lee, H.; Hahm, D.H. Rehmannia glutinosa ameliorates scopolamine-induced learning and memory impairment in rats. J. Microbiol. Biotechnol., 2011, 21(8), 874-783.
[46]
Mirshekar, M.; Roghani, M.; Khalili, M.; Baluchnejadmojarad, T. Chronic oral pelargonidin alleviates learning and memory disturbances in streptozotocin diabetic rats. Iran. J. Pharm. Res., 2011, 10(3), 569-575.
[47]
Hutson, P.H.; Finger, E.N.; Magliaro, B.C.; Smith, S.M.; Converso, A.; Sanderson, P.E. The selective phosphodiesterase 9 (PDE9) inhibitor PF-04447943 (6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)- pyrrolidin-3-yl]-1-(tetrahydro-2H-py ran-4-yl)-1,5-dihydro-4H-pyrazolo [3,4-d]pyrimidin-4-one) enhances synaptic plasticity and cognitive function in rodents. Neuropharmacology, 2011, 61(4), 665-676.
[48]
Baghel, M.S.; Thakur, M.K. Differential proteome profiling in the hippocampus of amnesic mice. Hippocampus, 2017, 27(8), 845-859.
[49]
Habiba, R.; Aamra, M.; Touqeer, A. Role of Cholinergic Receptors in Memory Retrieval Depends on Gender and Age of Memory. Behav. Brain Res., 2017, 331, 233-240.
[50]
Dela Pena, I.J.I.; Kim, H.J.; Botanas, C.J.; de la Pena, J.B.; Van Le, T.H.; Nguyen, M.D. The psychopharmacological activities of Vietnamese ginseng in mice: characterization of its psychomotor, sedative-hypnotic, antistress, anxiolytic, and cognitive effects. J. Ginseng Res., 2017, 41(2), 201-208.
[51]
Malikowska, N.; Salat, K.; Podkowa, A. Comparison of pro-amnesic efficacy of scopolamine, biperiden, and phencyclidine by using passive avoidance task in CD-1 mice. J. Pharmacol. Toxicol. Methods, 2017, 86, 76-80.
[52]
Pattanashetti, L.A.; Taranalli, A.D.; Parvatrao, V.; Malabade, R.H.; Kumar, D. Evaluation of neuroprotective effect of quercetin with donepezil in scopolamine-induced amnesia in rats. Indian J. Pharmacol., 2017, 49(1), 60-64.
[53]
Seo, J.Y.; Lim, S.S.; Kim, J.; Lee, K.W.; Kim, J.S. Alantolactone and Isoalantolactone Prevent Amyloid beta25-35 -induced Toxicity in Mouse Cortical Neurons and Scopolamine-induced Cognitive Impairment in Mice. Phytother. Res., 2017, 31(5), 801-811.
[54]
Kim, D.H.; Yoon, B.H.; Kim, Y.W.; Lee, S.; Shin, B.Y.; Jung, J.W. The seed extract of Cassia obtusifolia ameliorates learning and memory impairments induced by scopolamine or transient cerebral hypoperfusion in mice. J. Pharmacol. Sci., 2007, 105(1), 82-93.
[55]
Manalo, R.V.; Silvestre, M.A.; Barbosa, A.L.A.; Medina, P.M. Coconut (Cocos nucifera) Ethanolic Leaf Extract Reduces Amyloid-beta (1-42) Aggregation and Paralysis Prevalence in Transgenic Caenorhabditis elegans Independently of Free Radical Scavenging and Acetylcholinesterase Inhibition. Biomedicines, 2017, 5(2), pii: E17.
[56]
Babitha, P.P.; Sahila, M.M.; Bandaru, S.; Nayarisseri, A.; Sureshkumar, S. Molecular docking and pharmacological investigations of Rivastigmine-Fluoxetine and Coumarin-Tacrine hybrids against Acetyl Choline Esterase. Bioinformation, 2015, 11(8), 378-386.
[57]
McHardy, S.F.; Wang, H.L.; McCowen, S.V.; Valdez, M.C. Recent advances in acetylcholinesterase Inhibitors and Reactivators: an update on the patent literature (2012-2015). Expert Opin. Therapeut. Pat., 2017, 27(4), 455-476.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 19
ISSUE: 1
Year: 2019
Page: [72 - 78]
Pages: 7
DOI: 10.2174/1389557518666180716122608
Price: $58

Article Metrics

PDF: 16
HTML: 4