Recent Advances in Multi-target Anti-Alzheimer Disease Compounds (2013 Up to the Present)

Author(s): Ning Wang, Panpan Qiu, Wei Cui, Xiaojun Yan, Bin Zhang*, Shan He*

Journal Name: Current Medicinal Chemistry

Volume 26 , Issue 30 , 2019

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Since the last century, when scientists proposed the lock-and-key model, the discovery of drugs has focused on the development of drugs acting on single target. However, single-target drug therapies are not effective to complex diseases with multi-factorial pathogenesis. Moreover, the combination of single-target drugs readily causes drug resistance and side effects. In recent years, multi-target drugs have increasingly been represented among FDA-approved drugs. Alzheimer’s Disease (AD) is a complex and multi-factorial disease for which the precise molecular mechanisms are still not fully understood. In recent years, rational multi-target drug design methods, which combine the pharmacophores of multiple drugs, have been increasingly applied in the development of anti-AD drugs. In this review, we give a brief description of the pathogenesis of AD and provide detailed discussions about the recent development of chemical structures of anti-AD agents (2013 up to present) that have multiple targets, such as amyloid-β peptide, Tau protein, cholinesterases, monoamine oxidase, β-site amyloid-precursor protein-cleaving enzyme 1, free radicals, metal ions (Fe2+, Cu2+, Zn2+) and so on. In this paper, we also added some novel targets or possible pathogenesis which have been reported in recent years for AD therapy. We hope that these findings may provide new perspectives for the pharmacological treatment of AD.

Keywords: Alzheimer’s disease, pathogenesis, multi-target, design, synthesis, small molecule compounds.

Barbosa, M.; Valentão, P.; Andrade, P.B. Bioactive compounds from macroalgae in the new millennium: implications for neurodegenerative diseases. Mar. Drugs, 2014, 12(9), 4934-4972.
[] [PMID: 25257784]
Finder, V.H. Alzheimer’s disease: a general introduction and pathomechanism. J. Alzheimers Dis., 2010, 22(Suppl. 3), 5-19.
[] [PMID: 20858960]
Daulatzai, M.A. Early stages of pathogenesis in memory impairment during normal senescence and Alzheimer’s disease. J. Alzheimers Dis., 2010, 20(2), 355-367.
[] [PMID: 20164576]
Viegas, F.P.D.; Simões, M.C.R.; Rocha, M.D.D.; Castelli, M.R.; Moreira, M.S.; Junior, C.V. Alzheimer’s Disease: characterization, evolution and implications of the neuroinflammatory process. Rev. Virtual Quim., 2011, 3(4), 286-306.
Pinho, B.R.; Ferreres, F.; Valentão, P.; Andrade, P.B. Nature as a source of metabolites with cholinesterase-inhibitory activity: an approach to Alzheimer’s disease treatment. J. Pharm. Pharmacol., 2013, 65(12), 1681-1700.
[] [PMID: 24236980]
Uttara, B.; Singh, A.V.; Zamboni, P.; Mahajan, R.T. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr. Neuropharmacol., 2009, 7(1), 65-74.
[] [PMID: 19721819]
Mattson, M.P. Pathways towards and away from Alzheimer’s disease. Nature, 2004, 430(7000), 631-639.
[] [PMID: 15295589]
Hebert, L.E.; Scherr, P.A.; Bienias, J.L.; Bennett, D.A.; Evans, D.A. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch. Neurol., 2003, 60(8), 1119-1122.
[] [PMID: 12925369]
Ernst, R.L.; Hay, J.W. Economic research on Alzheimer disease: a review of the literature. Alzheimer Dis. Assoc. Disord., 1997, 11(Suppl. 6), 135-145.
[PMID: 9437458]
Weinreb, O.; Mandel, S.; Bar-Am, O.; Yogev-Falach, M.; Avramovich-Tirosh, Y.; Amit, T.; Youdim, M.B.H. Multifunctional neuroprotective derivatives of rasagiline as anti-Alzheimer’s disease drugs. Neurotherapeutics, 2009, 6(1), 163-174.
[] [PMID: 19110207]
Crismon, M.L. Tacrine: first drug approved for Alzheimer’s disease. Ann. Pharmacother., 1994, 28(6), 744-751.
[] [PMID: 7919566]
Bezerra da Silva, C.; Pott, A.; Elifio-Esposito, S.; Dalarmi, L.; Fialho do Nascimento, K.; Moura Burci, L.; de Oliveira, M.; de Fátima Gaspari Dias, J.; Warumby Zanin, S.M.; Gomes Miguel, O.; Dallarmi Miguel, M. Effect of Donepezil, Tacrine, Galantamine and Rivastigmine on acetylcholinesterase inhibition in Dugesia tigrina. Molecules, 2016, 21(1), 53.
[] [PMID: 26760993]
Tampi, R.R.; van Dyck, C.H. Memantine: efficacy and safety in mild-to-severe Alzheimer’s disease. Neuropsychiatr. Dis. Treat., 2007, 3(2), 245-258.
[] [PMID: 19300557]
Fan, L.Y.; Chiu, M.J. Combotherapy and current concepts as well as future strategies for the treatment of Alzheimer’s disease. Neuropsychiatr. Dis. Treat., 2014, 10(10), 439-451.
[PMID: 24648738]
Morphy, R.; Rankovic, Z. Designed multiple ligands. An emerging drug discovery paradigm. J. Med. Chem., 2005, 48(21), 6523-6543.
[] [PMID: 16220969]
Wermuth, C.G. Multitargeted drugs: the end of the “one-target-one-disease” philosophy? Drug Discov. Today, 2004, 9(19), 826-827.
[] [PMID: 15381132]
Reggiani, A.M.; Simoni, E.; Caporaso, R.; Meunier, J.; Keller, E.; Maurice, T.; Minarini, A.; Rosini, M.; Cavalli, A. In vivo characterization of ARN14140, a Memantine/Galantamine-based multi-target compound for Alzheimer’s disease. Sci. Rep., 2016, 6, 33172.
[] [PMID: 27609215]
Deng, Y.; Wang, Z.; Wang, R.; Zhang, X.; Zhang, S.; Wu, Y.; Staufenbiel, M.; Cai, F.; Song, W. Amyloid-β protein (Aβ) Glu11 is the major β-secretase site of β-site amyloid-β precursor protein-cleaving enzyme 1(BACE1), and shifting the cleavage site to Aβ Asp1 contributes to Alzheimer pathogenesis. Eur. J. Neurosci., 2013, 37(12), 1962-1969.
[] [PMID: 23773065]
Portelius, E.; Dean, R.A. Andreasson, U.; Mattsson, N.; Westerlund, A.; Olsson, M.; Demattos, R.B.; Racke, M.M.; Zetterberg, H.; May, P.C.; Blennow K. β-site amyloid precursor protein-cleavingenzyme 1(BACE1) inhibitor treatment induces Aβ5-X peptides through alternative amyloidprecursor protein cleavage. Alzheimers Res. Ther., 2014, 6, 75.
[] [PMID: 25404952]
Liu, H.; Li, Z.; Qiu, D.; Gu, Q.; Lei, Q.; Mao, L. The inhibitory effects of different curcuminoids on β-amyloid protein, β-amyloid precursor protein and β-site amyloid precursor protein cleaving enzyme 1 in swAPP HEK293 cells. Neurosci. Lett., 2010, 485(2), 83-88.
[] [PMID: 20727383]
Guzior, N.; Wieckowska, A.; Panek, D.; Malawska, B. Recent development of multifunctional agents as potential drug candidates for the treatment of Alzheimer’s disease. Curr. Med. Chem., 2015, 22(3), 373-404.
[] [PMID: 25386820]
Chakraborty, S.; Basu, S. Dual inhibition of BACE1 and Aβ aggregation by β-ecdysone: Application of a phytoecdysteroid scaffold in Alzheimer’s disease therapeutics. Int. J. Biol. Macromol., 2017, 95, 281-287.
[] [PMID: 27871792]
Chakraborty, S.; Basu, S. Multi-functional activities of citrus flavonoid narirutin in Alzheimer’s disease therapeutics: An integrated screening approach and in vitro validation. Int. J. Biol. Macromol., 2017, 103, 733-743.
[] [PMID: 28528948]
Chakraborty, S.; Bandyopadhyay, J.; Chakraborty, S.; Basu, S. Multi-target screening mines hesperidin as a multi-potent inhibitor: implication in Alzheimer’s disease therapeutics. Eur. J. Med. Chem., 2016, 121, 810-822.
[] [PMID: 27068363]
Alzheimer, A. About a peculiar disease of the cerebral cortex. By Alois Alzheimer, 1907 (Translated by L. Jarvik and H. Greenson). Alzheimer Dis. Assoc. Disord., 1987, 1(1), 3-8.
[PMID: 3331112]
Gong, C.X.; Liu, F.; Iqbal, K. Multifactorial hypothesis and multi-targets for Alzheimer’s disease. J. Alzheimers Dis., 2018, 64(s1), S107-S117.
[] [PMID: 29562523]
Sahoo, A.K.; Dandapat, J.; Dash, U.C.; Kanhar, S. Features and outcomes of drugs for combination therapy as multi-targets strategy to combat Alzheimer’s disease. J. Ethnopharmacol., 2018, 215, 42-73.
[] [PMID: 29248451]
Dos Santos Picanco, L.C.; Ozela, P.F.; de Fatima de Brito Brito, M.; Pinheiro, A.A.; Padilha, E.C.; Braga, F.S.; de Paula da Silva, C.H.T.; Dos Santos, C.B.R.; Rosa, J.M.C.; da Silva Hage-Melim, L.I. Alzheimer’s disease: a review from the pathophysiology to diagnosis, new perspectives for pharmacological treatment. Curr. Med. Chem., 2018, 25(26), 3141-3159.
[] [PMID: 30191777]
Batool, A.; Kamal, M.A.; Rizvi, S.M.D.; Rashid, S. Topical discoveries on multi-target approach to manage Alzheimer’s disease. Curr. Drug Metab., 2018, 19(8), 704-713.
[] [PMID: 29512457]
Roberson, E.D.; Scearce-Levie, K.; Palop, J.J.; Yan, F.; Cheng, I.H.; Wu, T.; Gerstein, H.; Yu, G.Q.; Mucke, L. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer’s disease mouse model. Science, 2007, 316(5825), 750-754.
[] [PMID: 17478722]
Mulder, C.; Scheltens, P.; Visser, J.J.; van Kamp, G.J.; Schutgens, R.B. Genetic and biochemical markers for Alzheimer’s disease: recent developments. Ann. Clin. Biochem., 2000, 37(Pt 5), 593-607.
[] [PMID: 11026514]
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(10), 165-188.
[] [PMID: 24148993]
Soto, C.; Brañes, M.C.; Alvarez, J.; Inestrosa, N.C. Structural determinants of the Alzheimer’s amyloid beta-peptide. J. Neurochem., 1994, 63(4), 1191-1198.
[] [PMID: 7931272]
Querfurth, H.W.; LaFerla, F.M. Alzheimer’s disease. N. Engl. J. Med., 2010, 362(4), 329-344.
[] [PMID: 20107219]
DeMattos, R.B.; Bales, K.R.; Cummins, D.J.; Dodart, J.C.; Paul, S.M.; Holtzman, D.M. Peripheral anti-A β antibody alters CNS and plasma A β clearance and decreases brain A β burden in a mouse model of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA, 2001, 98(15), 8850-8855.
[] [PMID: 11438712]
Näslund, J.; Schierhorn, A.; Hellman, U.; Lannfelt, L.; Roses, A.D.; Tjernberg, L.O.; Silberring, J.; Gandy, S.E.; Winblad, B.; Greengard, P. Relative abundance of Alzheimer A beta amyloid peptide variants in Alzheimer disease and normal aging. Proc. Natl. Acad. Sci. USA, 1994, 91(18), 8378-8382.
[] [PMID: 8078890]
Inestrosa, N.C.; Alvarez, A.; Pérez, C.A.; Moreno, R.D.; Vicente, M.; Linker, C.; Casanueva, O.I.; Soto, C.; Garrido, J. Acetylcholinesterase accelerates assembly of amyloid-β-peptides into Alzheimer’s fibrils: possible role of the peripheral site of the enzyme. Neuron, 1996, 16(4), 881-891.
[] [PMID: 8608006]
Nalbantoglu, J.; Lacoste-Royal, G.; Gauvreau, D. Genetic factors in Alzheimer’s disease. J. Am. Geriatr. Soc., 1990, 38(5), 564-568.
[] [PMID: 2185296]
Bertram, L.; Tanzi, R.E. Thirty years of Alzheimer’s disease genetics: the implications of systematic meta-analyses. Nat. Rev. Neurosci., 2008, 9(10), 768-778.
[] [PMID: 18802446]
Yu, J.T.; Mao, C.X.; Zhang, H.W.; Zhang, Q.; Wu, Z.C.; Yu, N.N.; Zhang, N.; Li, Y.; Tan, L. Genetic association of rs11610206 SNP on chromosome 12q13 with late-onset Alzheimer’s disease in a Han Chinese population. Clin. Chim. Acta, 2011, 412(1-2), 148-151.
[] [PMID: 20883677]
Sarter, M.; Parikh, V.; Howe, W.M. Phasic acetylcholine release and the volume transmission hypothesis: time to move on. Nat. Rev. Neurosci., 2009, 10(5), 383-390.
[] [PMID: 19377503]
Mineur, Y.S.; Picciotto, M.R. Nicotine receptors and depression: revisiting and revising the cholinergic hypothesis. Trends Pharmacol. Sci., 2010, 31(12), 580-586.
[] [PMID: 20965579]
Wilkinson, D.G.; Francis, P.T.; Schwam, E.; Payne-Parrish, J. Cholinesterase inhibitors used in the treatment of Alzheimer’s disease: the relationship between pharmacological effects and clinical efficacy. Drugs Aging, 2004, 21(7), 453-478.
[] [PMID: 15132713]
Musiał, A.; Bajda, M.; Malawska, B. Recent developments in cholinesterases inhibitors for Alzheimer’s disease treatment. Curr. Med. Chem., 2007, 14(25), 2654-2679.
[] [PMID: 17979717]
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.
[] [PMID: 27876467]
Spilovska, K.; Korabecny, J.; Kral, J.; Horova, A.; Musilek, K.; Soukup, O.; Drtinova, L.; Gazova, Z.; Siposova, K.; Kuca, K. 7-Methoxytacrine-adamantylamine heterodimers as cholinesterase inhibitors in Alzheimer’s disease treatment--synthesis, biological evaluation and molecular modeling studies. Molecules, 2013, 18(2), 2397-2418.
[] [PMID: 23429378]
da Costa, J.S.; Lopes, J.P.B.; Russowsky, D.; Petzhold, C.L.; Borges, A.C.; Ceschi, M.A.; Konrath, E.; Batassini, C.; Lunardi, P.S.; Gonçalves, C.A. Synthesis of tacrine-lophine hybrids via one-pot four component reaction and biological evaluation as acetyl- and butyrylcholinesterase inhibitors. Eur. J. Med. Chem., 2013, 62, 556-563.
[] [PMID: 23422935]
Chen, Y.; Lin, H.; Zhu, J.; Gu, K.; Li, Q.; He, S.; Lu, X.; Tan, R.; Pei, Y.; Wu, L.; Bian, Y.; Sun, H. Design, synthesis, in vitro and in vivo evaluation of tacrine–cinnamic acid hybrids as multi-target acetyl- and butyrylcholinesterase inhibitors against Alzheimer’s disease. RSC Advances, 2017, 7(54), 33851-33867.
Nadri, H.; Pirali-Hamedani, M.; Moradi, A.; Sakhteman, A.; Vahidi, A.; Sheibani, V.; Asadipour, A.; Hosseinzadeh, N.; Abdollahi, M.; Shafiee, A.; Foroumadi, A. 5,6-Dimethoxybenzofuran-3-one derivatives: a novel series of dual Acetylcholinesterase/Butyrylcholinesterase inhibitors bearing benzyl pyridinium moiety. Daru, 2013, 21(1), 15.
[] [PMID: 23445881]
Luo, Z.; Sheng, J.; Sun, Y.; Lu, C.; Yan, J.; Liu, A.; Luo, H.B.; Huang, L.; Li, X. Synthesis and evaluation of multi-target-directed ligands against Alzheimer’s disease based on the fusion of donepezil and ebselen. J. Med. Chem., 2013, 56(22), 9089-9099.
[] [PMID: 24160297]
Khoobi, M.; Alipour, M.; Moradi, A.; Sakhteman, A.; Nadri, H.; Razavi, S.F.; Ghandi, M.; Foroumadi, A.; Shafiee, A. Design, synthesis, docking study and biological evaluation of some novel tetrahydrochromeno [3′,4′:5,6]pyrano[2,3-b]quinolin-6(7H)-one derivatives against acetyl- and butyrylcholinesterase. Eur. J. Med. Chem., 2013, 68(12), 291-300.
[] [PMID: 23988412]
Asadipour, A.; Alipour, M.; Jafari, M.; Khoobi, M.; Emami, S.; Nadri, H.; Sakhteman, A.; Moradi, A.; Sheibani, V.; Homayouni Moghadam, F.; Shafiee, A.; Foroumadi, A. Novel coumarin-3-carboxamides bearing N-benzylpiperidine moiety as potent acetylcholinesterase inhibitors. Eur. J. Med. Chem., 2013, 70(12), 623-630.
[] [PMID: 24211638]
Pourshojaei, Y.; Gouranourimi, A.; Hekmat, S.; Asadipour, A.; Rahmani-Nezhad, S.; Moradi, A.; Nadri, H.; Moghadam, F.H.; Emami, S.; Foroumadi, A.; Shafiee, A. Design, synthesis and anticholinesterase activity of novel benzylidenechroman-4-ones bearing cyclic amine side chain. Eur. J. Med. Chem., 2015, 97, 181-189.
[] [PMID: 25969170]
Khoobi, M.; Ghanoni, F.; Nadri, H.; Moradi, A.; Pirali Hamedani, M.; Homayouni Moghadam, F.; Emami, S.; Vosooghi, M.; Zadmard, R.; Foroumadi, A.; Shafiee, A. New tetracyclic tacrine analogs containing pyrano[2,3-c]pyrazole: efficient synthesis, biological assessment and docking simulation study. Eur. J. Med. Chem., 2015, 89, 296-303.
[] [PMID: 25462245]
Ghanei-Nasab, S.; Khoobi, M.; Hadizadeh, F.; Marjani, A.; Moradi, A.; Nadri, H.; Emami, S.; Foroumadi, A.; Shafiee, A. Synthesis and anticholinesterase activity of coumarin-3-carboxamides bearing tryptamine moiety. Eur. J. Med. Chem., 2016, 121, 40-46.
[] [PMID: 27214510]
Alipour, M.; Khoobi, M.; Moradi, A.; Nadri, H.; Homayouni Moghadam, F.; Emami, S.; Hasanpour, Z.; Foroumadi, A.; Shafiee, A. Synthesis and anti-cholinesterase activity of new 7-hydroxycoumarin derivatives. Eur. J. Med. Chem., 2014, 82(16), 536-544.
[] [PMID: 24941128]
Xu, W.; Wang, X.B.; Wang, Z.M.; Wu, J.J.; Li, F.; Wang, J.; Kong, L.Y. Synthesis and evaluation of donepezil–ferulic acid hybrids as multi-target-directed ligands against Alzheimer’s disease. MedChemComm, 2016, 7(5), 990-998.
Teponnou, G.A.K.; Joubert, J.; Malan, S.F. Tacrine, Trolox and Tryptoline as lead compounds for the design and synthesis of multi-target agents for Alzheimer’s disease therapy. Open Med. Chem. J., 2017, 11(1), 24-37.
[] [PMID: 28567126]
Shidore, M.; Machhi, J.; Shingala, K.; Murumkar, P.; Sharma, M.K.; Agrawal, N.; Tripathi, A.; Parikh, Z.; Pillai, P.; Yadav, M.R. Benzylpiperidine-linked diarylthiazoles as potential anti-Alzheimer’s agents: synthesis and biological evaluation. J. Med. Chem., 2016, 59(12), 5823-5846.
[] [PMID: 27253679]
Terry, A.V., Jr; Buccafusco, J.J. The cholinergic hypothesis of age and Alzheimer’s disease-related cognitive deficits: recent challenges and their implications for novel drug development. J. Pharmacol. Exp. Ther., 2003, 306(3), 821-827.
[] [PMID: 12805474]
Xie, S.S.; Wang, X.B.; Li, J.Y.; Yang, L.; Kong, L.Y. Design, synthesis and evaluation of novel tacrine-coumarin hybrids as multifunctional cholinesterase inhibitors against Alzheimer’s disease. Eur. J. Med. Chem., 2013, 64, 540-553.
[] [PMID: 23685572]
Terry, A.V., Jr; Buccafusco, J.J.; Wilson, C. Cognitive dysfunction in neuropsychiatric disorders: selected serotonin receptor subtypes as therapeutic targets. Behav. Brain Res., 2008, 195(1), 30-38.
[] [PMID: 18241938]
Garcia-Alloza, M.; Gil-Bea, F.J.; Diez-Ariza, M.; Chen, C.P.; Francis, P.T.; Lasheras, B.; Ramirez, M.J. Cholinergic-serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer’s disease. Neuropsychologia, 2005, 43(3), 442-449.
[] [PMID: 15707619]
Razzaghi-Asl, N.; Shahabipour, S.; Ebadi, A.; Bagheri, A. Quantum chemical analysis of potential anti-parkinson agents. J. Chem. Sci., 2015, 127(7), 1211-1220.
Son, S.Y.; Ma, J.; Kondou, Y.; Yoshimura, M.; Yamashita, E.; Tsukihara, T. Structure of human monoamine oxidase A at 2.2-A resolution: the control of opening the entry for substrates/inhibitors. Proc. Natl. Acad. Sci. USA, 2008, 105(15), 5739-5744.
[] [PMID: 18391214]
Gasser, T.; Wichmann, T.; Delong, M.R. Chapter 19 - Parkinson disease and other synucleinopathies. In Neurobiology of Brain Disorders; , 2015, pp. 281-302.
Kumar, A.; Jain, S.; Parle, M.; Jain, N.; Kumar, P. 3-Aryl-1-phenyl-1H-pyrazole derivatives as new multitarget directed ligands for the treatment of Alzheimer’s disease, with acetylcholinesterase and monoamine oxidase inhibitory properties. EXCLI J., 2013, 12, 1030-1042.
[PMID: 27298613]
Lan, J.S.; Ding, Y.; Liu, Y.; Kang, P.; Hou, J.W.; Zhang, X.Y.; Xie, S.S.; Zhang, T. Design, synthesis and biological evaluation of novel coumarin-N-benzyl pyridinium hybrids as multi-target agents for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2017, 139, 48-59.
[] [PMID: 28797883]
Xie, S.S.; Lan, J.S.; Wang, X.; Wang, Z.M.; Jiang, N.; Li, F.; Wu, J.J.; Wang, J.; Kong, L.Y. Design, synthesis and biological evaluation of novel donepezil-coumarin hybrids as multi-target agents for the treatment of Alzheimer’s disease. Bioorg. Med. Chem., 2016, 24(7), 1528-1539.
[] [PMID: 26917219]
Bolea, I.; Gella, A.; Monjas, L.; Pérez, C.; Rodríguez-Franco, M.I.; Marco-Contelles, J.; Samadi, A.; Unzeta, M. Multipotent, permeable drug ASS234 inhibits Aβ aggregation, possesses antioxidant properties and protects from Aβ-induced apoptosis in vitro. Curr. Alzheimer Res., 2013, 10(8), 797-808.
[] [PMID: 23919774]
Unzeta, M.; Esteban, G.; Bolea, I.; Fogel, W.A.; Ramsay, R.R.; Youdim, M.B.H.; Tipton, K.F.; Marco-Contelles, J. Multi-target directed donepezil-like ligands for Alzheimer’s disease. Front. Neurosci., 2016, 10(112), 205.
[] [PMID: 27252617]
Bautista-Aguilera, O.M.; Esteban, G.; Chioua, M.; Nikolic, K.; Agbaba, D.; Moraleda, I.; Iriepa, I.; Soriano, E.; Samadi, A.; Unzeta, M.; Marco-Contelles, J. Multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer’s disease: design, synthesis, biochemical evaluation, ADMET, molecular modeling, and QSAR analysis of novel donepezil-pyridyl hybrids. Drug Des. Devel. Ther., 2014, 8, 1893-1910.
[] [PMID: 25378907]
Bautista-Aguilera, O.M.; Esteban, G.; Bolea, I.; Nikolic, K.; Agbaba, D.; Moraleda, I.; Iriepa, I.; Samadi, A.; Soriano, E.; Unzeta, M.; Marco-Contelles, J. Design, synthesis, pharmacological evaluation, QSAR analysis, molecular modeling and ADMET of novel donepezil-indolyl hybrids as multipotent cholinesterase/monoamine oxidase inhibitors for the potential treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2014, 75, 82-95.
[] [PMID: 24530494]
Pisani, L.; Farina, R.; Soto-Otero, R.; Denora, N.; Mangiatordi, G.F.; Nicolotti, O.; Mendez-Alvarez, E.; Altomare, C.D.; Catto, M.; Carotti, A. Searching for multi-targeting neurotherapeutics against Alzheimer’s: discovery of potent AChE-MAO B inhibitors through the decoration of the 2H-Chromen-2-one structural motif. Molecules, 2016, 21(3), 362.
[] [PMID: 26999091]
Matos, M.J.; Janeiro, P.; González Franco, R.M.; Vilar, S.; Tatonetti, N.P.; Santana, L.; Uriarte, E.; Borges, F.; Fontenla, J.A.; Viña, D. Synthesis, pharmacological study and docking calculations of new benzo[f]coumarin derivatives as dual inhibitors of enzymatic systems involved in neurodegenerative diseases. Future Med. Chem., 2014, 6(4), 371-383.
[] [PMID: 24635520]
Xie, S.S.; Wang, X.; Jiang, N.; Yu, W.; Wang, K.D.; Lan, J.S.; Li, Z.R.; Kong, L.Y. Multi-target tacrine-coumarin hybrids: cholinesterase and monoamine oxidase B inhibition properties against Alzheimer’s disease. Eur. J. Med. Chem., 2015, 95, 153-165.
[] [PMID: 25812965]
Rosini, M.; Simoni, E.; Bartolini, M.; Cavalli, A.; Ceccarini, L.; Pascu, N.; McClymont, D.W.; Tarozzi, A.; Bolognesi, M.L.; Minarini, A.; Tumiatti, V.; Andrisano, V.; Mellor, I.R.; Melchiorre, C. Inhibition of acetylcholinesterase, beta-amyloid aggregation, and NMDA receptors in Alzheimer’s disease: a promising direction for the multi-target-directed ligands gold rush. J. Med. Chem., 2008, 51(15), 4381-4384.
[] [PMID: 18605718]
Huang, L.; Su, T.; Shan, W.; Luo, Z.; Sun, Y.; He, F.; Li, X. Inhibition of cholinesterase activity and amyloid aggregation by berberine-phenyl-benzoheterocyclic and tacrine-phenyl-benzoheterocyclic hybrids. Bioorg. Med. Chem., 2012, 20(9), 3038-3048.
[] [PMID: 22472046]
Zhao, X.J.; Gong, D.M.; Jiang, Y.R.; Guo, D.; Zhu, Y.; Deng, Y.C. Multipotent AChE and BACE-1 inhibitors for the treatment of Alzheimer’s disease: design, synthesis and bio-analysis of 7-amino-1,4-dihydro-2H-isoquilin-3-one derivates. Eur. J. Med. Chem., 2017, 138, 738-747.
[] [PMID: 28728106]
Chen, Y.; Sun, J.; Peng, S.; Liao, H.; Zhang, Y.; Lehmann, J. Tacrine-flurbiprofen hybrids as multifunctional drug candidates for the treatment of Alzheimer’s disease. Arch. Pharm. (Weinheim), 2013, 346(12), 865-871.
[] [PMID: 24203864]
Jeřábek, J.; Uliassi, E.; Guidotti, L.; Korábečný, J.; Soukup, O.; Sepsova, V.; Hrabinova, M.; Kuča, K.; Bartolini, M.; Peña-Altamira, L.E.; Petralla, S.; Monti, B.; Roberti, M.; Bolognesi, M.L. Tacrine-resveratrol fused hybrids as multi-target-directed ligands against Alzheimer’s disease. Eur. J. Med. Chem., 2017, 127, 250-262.
[] [PMID: 28064079]
Keri, R.S.; Quintanova, C.; Marques, S.M.; Esteves, A.R.; Cardoso, S.M.; Santos, M.A. Design, synthesis and neuroprotective evaluation of novel tacrine-benzothiazole hybrids as multi-targeted compounds against Alzheimer’s disease. Bioorg. Med. Chem., 2013, 21(15), 4559-4569.
[] [PMID: 23768661]
Butini, S.; Brindisi, M.; Brogi, S.; Maramai, S.; Guarino, E.; Panico, A.; Saxena, A.; Chauhan, V.; Colombo, R.; Verga, L.; De Lorenzi, E.; Bartolini, M.; Andrisano, V.; Novellino, E.; Campiani, G.; Gemma, S. Multifunctional cholinesterase and amyloid Beta fibrillization modulators. Synthesis and biological investigation. ACS Med. Chem. Lett., 2013, 4(12), 1178-1182.
[] [PMID: 24900626]
Zhang, C.; Du, Q.Y.; Chen, L.D.; Wu, W.H.; Liao, S.Y.; Yu, L.H.; Liang, X.T. Design, synthesis and evaluation of novel tacrine-multialkoxybenzene hybrids as multi-targeted compounds against Alzheimer’s disease. Eur. J. Med. Chem., 2016, 116, 200-209.
[] [PMID: 27061983]
Gazova, Z.; Soukup, O.; Sepsova, V.; Siposova, K.; Drtinova, L.; Jost, P.; Spilovska, K.; Korabecny, J.; Nepovimova, E.; Fedunova, D.; Horak, M.; Kaniakova, M.; Wang, Z.J.; Hamouda, A.K.; Kuca, K. Multi-target-directed therapeutic potential of 7-methoxytacrine-adamantylamine heterodimers in the Alzheimer’s disease treatment. Biochim. Biophys. Acta Mol. Basis Dis., 2017, 1863(2), 607-619.
[] [PMID: 27865910]
Hernández-Rodríguez, M.; Correa-Basurto, J.; Martínez-Ramos, F.; Padilla-Martínez, I.I.; Benítez-Cardoza, C.G.; Mera-Jiménez, E.; Rosales-Hernández, M.C. Design of multi-target compounds as AChE, BACE1, and amyloid-β(1-42) oligomerization inhibitors: in silico and in vitro studies. J. Alzheimers Dis., 2014, 41(4), 1073-1085.
[] [PMID: 24762947]
Li, Y.; Peng, P.; Tang, L.; Hu, Y.; Hu, Y.; Sheng, R. Design, synthesis and evaluation of rivastigmine and curcumin hybrids as site-activated multitarget-directed ligands for Alzheimer’s disease therapy. Bioorg. Med. Chem., 2014, 22(17), 4717-4725.
[] [PMID: 25082512]
Li, R.S.; Wang, X.B.; Hu, X.J.; Kong, L.Y. Design, synthesis and evaluation of flavonoid derivatives as potential multifunctional acetylcholinesterase inhibitors against Alzheimer’s disease. Bioorg. Med. Chem. Lett., 2013, 23(9), 2636-2641.
[] [PMID: 23511019]
Huang, L.; Miao, H.; Sun, Y.; Meng, F.; Li, X. Discovery of indanone derivatives as multi-target-directed ligands against Alzheimer’s disease. Eur. J. Med. Chem., 2014, 87(87), 429-439.
[] [PMID: 25282266]
Mishra, C.B.; Kumari, S.; Manral, A.; Prakash, A.; Saini, V.; Lynn, A.M.; Tiwari, M. Design, synthesis, in-silico and biological evaluation of novel donepezil derivatives as multi-target-directed ligands for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2017, 125, 736-750.
[] [PMID: 27721157]
Meena, P.; Nemaysh, V.; Khatri, M.; Manral, A.; Luthra, P.M.; Tiwari, M. Synthesis, biological evaluation and molecular docking study of novel piperidine and piperazine derivatives as multi-targeted agents to treat Alzheimer’s disease. Bioorg. Med. Chem., 2015, 23(5), 1135-1148.
[] [PMID: 25624107]
Prati, F.; Bergamini, C.; Fato, R.; Soukup, O.; Korabecny, J.; Andrisano, V.; Bartolini, M.; Bolognesi, M.L. Novel 8‐hydroxyquinoline derivatives as multitarget compounds for the treatment of Alzheimer′s disease. ChemMedChem, 2016, 11(12), 1284-1295.
[] [PMID: 26880501]
Ozadali-Sari, K.; Tüylü Küçükkılınç, T.; Ayazgok, B.; Balkan, A.; Unsal-Tan, O. Novel multi-targeted agents for Alzheimer’s disease: Synthesis, biological evaluation, and molecular modeling of novel 2-[4-(4-substitutedpiperazin-1-yl)phenyl]benzimidazoles. Bioorg. Chem., 2017, 72, 208-214.
[] [PMID: 28478328]
Horton, W.; Sood, A.; Peerannawar, S.; Kugyela, N.; Kulkarni, A.; Tulsan, R.; Tran, C.D.; Soule, J.; LeVine, H., III; Török, B.; Török, M. Synthesis and application of β-carbolines as novel multi-functional anti-Alzheimer’s disease agents. Bioorg. Med. Chem. Lett., 2017, 27(2), 232-236.
[] [PMID: 27923619]
Bajda, M.; Guzior, N.; Ignasik, M.; Malawska, B. Multi-target-directed ligands in Alzheimer’s disease treatment. Curr. Med. Chem., 2011, 18(32), 4949-4975.
[] [PMID: 22050745]
González-Naranjo, P.; Pérez-Macias, N.; Campillo, N.E.; Pérez, C.; Arán, V.J.; Girón, R.; Sánchez-Robles, E.; Martín, M.I.; Gómez-Cañas, M.; García-Arencibia, M.; Fernández-Ruiz, J.; Páez, J.A. Cannabinoid agonists showing BuChE inhibition as potential therapeutic agents for Alzheimer’s disease. Eur. J. Med. Chem., 2014, 73, 56-72.
[] [PMID: 24378710]
Rosini, M.; Simoni, E.; Minarini, A.; Melchiorre, C. Multi-target design strategies in the context of Alzheimer’s disease: acetylcholinesterase inhibition and NMDA receptor antagonism as the driving forces. Neurochem. Res., 2014, 39(10), 1914-1923.
[] [PMID: 24493627]
Viayna, E.; Sola, I.; Bartolini, M.; De Simone, A.; Tapia-Rojas, C.; Serrano, F.G.; Sabaté, R.; Juárez-Jiménez, J.; Pérez, B.; Luque, F.J.; Andrisano, V.; Clos, M.V.; Inestrosa, N.C.; Muñoz-Torrero, D. Synthesis and multitarget biological profiling of a novel family of rhein derivatives as disease-modifying anti-Alzheimer agents. J. Med. Chem., 2014, 57(6), 2549-2567.
[] [PMID: 24568372]
Zhou, L.Y.; Zhu, Y.; Jiang, Y.R.; Zhao, X.J.; Guo, D. Design, synthesis and biological evaluation of dual acetylcholinesterase and phosphodiesterase 5A inhibitors in treatment for Alzheimer’s disease. Bioorg. Med. Chem. Lett., 2017, 27(17), 4180-4184.
[] [PMID: 28751142]
Singh, M.; Kaur, M.; Singh, N.; Silakari, O. Exploration of multi-target potential of chromen-4-one based compounds in Alzheimer’s disease: Design, synthesis and biological evaluations. Bioorg. Med. Chem., 2017, 25(24), 6273-6285.
[] [PMID: 29089261]
Rodríguez, J.J.; Noristani, H.N.; Verkhratsky, A. The serotonergic system in ageing and Alzheimer’s disease. Prog. Neurobiol., 2012, 99(1), 15-41.
[] [PMID: 22766041]
Geldenhuys, W.J.; Van der Schyf, C.J. Role of serotonin in Alzheimer’s disease: a new therapeutic target? CNS Drugs, 2011, 25(9), 765-781.
[] [PMID: 21870888]
Verdurand, M.; Zimmer, L. Hippocampal 5-HT1A receptor expression changes in prodromal stages of Alzheimer’s disease: Beneficial or deleterious? Neuropharmacology, 2017, 123, 446-454.
[] [PMID: 28647411]
Spigset, O.; Wilhelmsson, C.; Mjörndal, T.; Eriksson, S. Serotonin 5-HT2A receptor binding in platelets from patients with Alzheimer’s disease or vascular dementia. Int. Psychogeriatr., 2000, 12(4), 537-545.
[] [PMID: 11263719]
Spencer, J.P.; Brown, J.T.; Richardson, J.C.; Medhurst, A.D.; Sehmi, S.S.; Calver, A.R.; Randall, A.D. Modulation of hippocampal excitability by 5-HT4 receptor agonists persists in a transgenic model of Alzheimer’s disease. Neuroscience, 2004, 129(1), 49-54.
[] [PMID: 15489027]
Upton, N.; Chuang, T.T.; Hunter, A.J.; Virley, D.J. 5-HT6 receptor antagonists as novel cognitive enhancing agents for Alzheimer’s disease. Neurotherapeutics, 2008, 5(3), 458-469.
[] [PMID: 18625457]
Andrews, M.; Tousi, B.; Sabbagh, M.N. 5HT6 antagonists in the treatment of Alzheimer’s dementia: current progress. Neurol. Ther., 2018, 7(1), 51-58.
[] [PMID: 29728891]
Więckowska, A.; Kołaczkowski, M.; Bucki, A.; Godyń, J.; Marcinkowska, M.; Więckowski, K.; Zaręba, P.; Siwek, A.; Kazek, G.; Głuch-Lutwin, M.; Mierzejewski, P.; Bienkowski, P.; Sienkiewicz-Jarosz, H.; Knez, D.; Wichur, T.; Gobec, S.; Malawska, B. Novel multi-target-directed ligands for Alzheimer’s disease: combining cholinesterase inhibitors and 5-HT6 receptor antagonists. Design, synthesis and biological evaluation. Eur. J. Med. Chem., 2016, 124, 63-81.
[] [PMID: 27560283]
Digiacomo, M.; Chen, Z.; Wang, S.; Lapucci, A.; Macchia, M.; Yang, X.; Chu, J.; Han, Y.; Pi, R.; Rapposelli, S. Syn-thesis and pharmacological evaluation of multifunctional tacrine derivatives against several disease pathways of AD. Bioorg. Med. Chem. Lett., 2015, 25(4), 807-810.
[] [PMID: 25597007]
Lukiw, W.J. Emerging amyloid beta (Ab) peptide modulators for the treatment of Alzheimer’s disease (AD). Expert Opin. Emerg. Drugs, 2008, 13(2), 255-271.
[] [PMID: 18537520]
Ling, S.; Zhou, J.; Rudd, J.A.; Hu, Z.; Fang, M. The recent updates of therapeutic approaches against aβ for the treatment of Alzheimer’s disease. Anat. Rec. (Hoboken), 2011, 294(8), 1307-1318.
[] [PMID: 21717585]
Liu, K.; Chojnacki, J.E.; Wade, E.E.; Saathoff, J.M.; Lesnefsky, E.J.; Chen, Q.; Zhang, S. Bivalent compound 17MN exerts neuroprotection through interaction at multiple sites in a cellular model of Alzheimer’s disease. J. Alzheimers Dis., 2015, 47(4), 1021-1033.
[] [PMID: 26401780]
Mao, F.; Yan, J.; Li, J.; Jia, X.; Miao, H.; Sun, Y.; Huang, L.; Li, X. New multi-target-directed small molecules against Alzheimer’s disease: a combination of resveratrol and clioquinol. Org. Biomol. Chem., 2014, 12(31), 5936-5944.
[] [PMID: 24986600]
Wang, Z.; Li, W.; Wang, Y.; Li, X.; Huang, L.; Li, X. Design, synthesis and evaluation of clioquinol-ebselen hybrids as multi-target-directed ligands against Alzheimer’s disease. Rsc Adv., 2016, 6(9), 7139-7158.
Gurav, A.N. Alzheimer’s disease and periodontitis--an elusive link. Rev Assoc Med Bras (1992),, 2014, 60(2), 173-180.
[] [PMID: 24919005]
Hernández-Rodríguez, M.; Correa-Basurto, J.; Martínez-Ramos, F.; Padilla-Martínez, I.I.; Benítez-Cardoza, C.G.; Mera-Jiménez, E.; Rosales-Hernández, M.C. Design of multi-target compounds as AChE, BACE1, and amyloid-β(1-42) oligomerization inhibitors: in silico and in vitro studies. J. Alzheimers Dis., 2014, 41(4), 1073-1085.
[] [PMID: 24762947]
Flesch, D.; Ness, J.; Lamers, C.; Dehm, F.; Popella, S.; Steri, R.; Ogorek, I.; Hieke, M.; Dannhardt, G.; Werz, O.; Weggen, S.; Schubert-Zsilavecz, M. SAR-studies of γ-secretase modulators with PPARγ-agonistic and 5-lipoxygenase-inhibitory activity for Alzheimer’s disease. Bioorg. Med. Chem. Lett., 2015, 25(4), 841-846.
[] [PMID: 25575659]
Thomas, M.P.; Erneux, C.; Potter, B.V. SHIP2: structure, function and inhibition. ChemBioChem, 2017, 18(3), 233-247.
[] [PMID: 27907247]
Kam, T.I.; Park, H.; Gwon, Y.; Song, S.; Kim, S.H.; Moon, S.W.; Jo, D.G.; Jung, Y.K. FcγRIIb-SHIP2 axis links Aβ to tau pathology by disrupting phosphoinositide metabolism in Alzheimer’s disease model. eLife,, 2016, 5e18691.
[] [PMID: 27834631]
Kam, T.I.; Song, S.; Gwon, Y.; Park, H.; Yan, J.J. Im, I.; Choi, J.W.; Choi, T.Y.; Kim, J.; Song, D.K.; Takai, T.; Kim, Y.C.; Kim, K.S.; Choi, S.Y.; Choi, S.; Klein, W.L.; Yuan, J.; Jung, Y.K. FcγRIIb mediates amyloid-β neurotoxicity and memory impairment in Alzheimer’s disease. J. Clin. Invest., 2013, 123(7), 2791-2802.
[] [PMID: 23921129]
Mostafavi, S.; Gaiteri, C.; Sullivan, S.E.; White, C.C.; Tasaki, S.; Xu, J.; Taga, M.; Klein, H.U.; Patrick, E.; Komashko, V.; McCabe, C.; Smith, R.; Bradshaw, E.M.; Root, D.E.; Regev, A.; Yu, L.; Chibnik, L.B.; Schneider, J.A.; Young-Pearse, T.L.; Bennett, D.A.; De Jager, P.L. A molecular network of the aging human brain provides insights into the pathology and cognitive decline of Alzheimer’s disease. Nat. Neurosci., 2018, 21(6), 811-819.
[] [PMID: 29802388]
Lim, J.W.; Kim, S.K.; Choi, S.Y.; Kim, D.H.; Gadhe, C.G.; Lee, H.N.; Kim, H.J.; Kim, J.; Cho, S.J.; Hwang, H.; Seong, J.; Jeong, K.S.; Lee, J.Y.; Lim, S.M.; Lee, J.W.; Pae, A.N. Identification of crizotinib derivatives as potent SHIP2 inhibitors for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2018, 157, 405-422.
[] [PMID: 30103190]
Di Domenico, F.; Tramutola, A.; Butterfield, D.A. Role of 4-hydroxy-2-nonenal (HNE) in the pathogenesis of Alzheimer’s disease and other selected age-related neurodegenerative disorders. Free Radic. Biol. Med., 2017, 111, 253-261.
[] [PMID: 27789292]
Raz, N.; Daugherty, A.M. Pathways to brain aging and their modifiers: Free-radical-induced energetic and neural decline in senescence (FRIENDS) model - A Mini-Review. Gerontology, 2018, 64(1), 49-57.
[] [PMID: 28858861]
Thiratmatrakul, S.; Yenjai, C.; Waiwut, P.; Vajragupta, O.; Reubroycharoen, P.; Tohda, M.; Boonyarat, C. Synthesis, biological evaluation and molecular modeling study of novel tacrine-carbazole hybrids as potential multifunctional agents for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2014, 75(1), 21-30.
[] [PMID: 24508831]
Yang, G.X.; Ge, S.L.; Wu, Y.; Huang, J.; Li, S.L.; Wang, R.; Ma, L. Design, synthesis and biological evaluation of 3-piperazinecarboxylate sarsasapogenin derivatives as potential multifunctional anti-Alzheimer agents. Eur. J. Med. Chem., 2018, 156, 206-215.
[] [PMID: 30006165]
Jalili-Baleh, L.; Forootanfar, H.; Küçükkılınç, T.T.; Nadri, H.; Abdolahi, Z.; Ameri, A.; Jafari, M.; Ayazgok, B.; Baeeri, M.; Rahimifard, M.; Abbas Bukhari, S.N.; Abdollahi, M.; Ganjali, M.R.; Emami, S.; Khoobi, M.; Foroumadi, A. Design, synthesis and evaluation of novel multi-target-directed ligands for treatment of Alzheimer’s disease based on coumarin and lipoic acid scaffolds. Eur. J. Med. Chem., 2018, 152, 600-614.
[] [PMID: 29763808]
Bolós, M.; Perea, J.R.; Avila, J. Alzheimer’s disease as an inflammatory disease. Biomol. Concepts, 2017, 8(1), 37-43.
[] [PMID: 28231054]
Zhu, M.; Wang, X.; Sun, L.; Schultzberg, M.; Hjorth, E. Can inflammation be resolved in Alzheimer’s disease? Ther. Adv. Neurol. Disorder., 2018, 111756286418791107
[] [PMID: 30116300]
Spangenberg, E.E.; Green, K.N. Inflammation in Alzheimer’s disease: lessons learned from microglia-depletion models. Brain Behav. Immun., 2017, 61, 1-11.
[] [PMID: 27395435]
Daugherty, D.; Goldberg, J.; Fischer, W.; Dargusch, R.; Maher, P.; Schubert, D. A novel Alzheimer’s disease drug candidate targeting inflammation and fatty acid metabolism. Alzheimers Res. Ther., 2017, 9(1), 50.
[] [PMID: 28709449]
Fu, W.; Patel, A.; Kimura, R.; Soudy, R.; Jhamandas, J.H. Amylin receptor: A potential therapeutic target for Alzheimer’s disease. Trends Mol. Med., 2017, 23(8), 709-720.
[] [PMID: 28694141]
Soudy, R.; Patel, A.; Fu, W.; Kaur, K.; MacTavish, D.; Westaway, D.; Davey, R.; Zajac, J.; Jhamandas, J. Cyclic AC253, a novel amylin receptor antagonist, improves cognitive deficits in a mouse model of Alzheimer’s disease. Alzheimers Dement. (N. Y.), 2016, 3(1), 44-56.
[] [PMID: 29067318]
Fulop, T.; Witkowski, J.M.; Bourgade, K.; Khalil, A.; Zerif, E.; Larbi, A.; Hirokawa, K.; Pawelec, G.; Bocti, C.; Lacombe, G.; Dupuis, G.; Frost, E.H. Can an infection hypothesis explain the β Amyloid hypothesis of Alzheimer’s disease? Front. Aging Neurosci., 2018, 10, 224.
[] [PMID: 30087609]
Zhao, Y.; Jaber, V.; Lukiw, W.J. Secretory products of the human GI tract microbiome and their potential impact on Alzheimer’s disease (AD): detection of Lipopolysaccharide (LPS) in AD hippocampus. Front. Cell. Infect. Microbiol., 2017, 7, 318.
[] [PMID: 28744452]
Harris, S.A.; Harris, E.A. Molecular mechanisms for herpes simplex virus type 1 pathogenesis in Alzheimer’s disease. Front. Aging Neurosci., 2018, 10, 48.
[] [PMID: 29559905]
Kandimalla, R.; Thirumala, V.; Reddy, P.H. Is Alzheimer’s disease a Type 3 diabetes? A critical appraisal. Biochim. Biophys. Acta Mol. Basis Dis., 2017, 1863(5), 1078-1089.
[] [PMID: 27567931]
Kaminari, A.; Tsilibary, E.C.; Tzinia, A. A new perspective in utilizing MMP-9 as a therapeutic target for Alzheimer’s disease and type 2 diabetes mellitus. J. Alzheimers Dis., 2018, 64(1), 1-16.
[] [PMID: 29865065]
Chakraborty, S. Multi-potent natural scaffolds targeting amyloid cascade: In search of Alzheimer’s disease therapeutics. Curr. Top. Med. Chem., 2017, 17(31), 3336-3348.
[] [PMID: 29345580]
Ambure, P.; Roy, K. CADD modeling of multi-target drugs against Alzheimer’s disease. Curr. Drug Targets, 2017, 18(5), 522-533.
[] [PMID: 26343117]
Abeijón, P.; García-Mera, X.; Caamaño, O.; Yañez, M.; López-Castro, E.; Romero-Durán, F.J.; González-Díaz, H. Multi-target mining of alzheimer disease proteome with Hansch’s QSBR-perturbation theory and experimental-theoretic study of new thiophene isosters of rasagiline. Curr. Drug Targets, 2017, 18(5), 511-521.
[] [PMID: 26521774]
Shao, Z.Q. Comparison of the efficacy of four cholinesterase inhibitors in combination with memantine for the treatment of Alzheimer’s disease. Int. J. Clin. Exp. Med., 2015, 8(2), 2944-2948.
[PMID: 25932260]
Klatte, E.T.; Scharre, D.W.; Nagaraja, H.N.; Davis, R.A.; Beversdorf, D.Q. Combination therapy of donepezil and vitamin E in Alzheimer disease. Alzheimer Dis. Assoc. Disord., 2003, 17(2), 113-116.
[] [PMID: 12794389]

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Year: 2019
Published on: 03 December, 2018
Page: [5684 - 5710]
Pages: 27
DOI: 10.2174/0929867326666181203124102
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