A review on cholinesterase inhibitors for Alzheimer’s disease

다국어 초록 (Multilingual Abstract)

Alzheimer’s disease (AD), a progressiveneurodegenerative disorder, is characterized by the deficitsin the cholinergic system and deposition of beta amyloid(Ab) in the form of neurofibrillary tangles and amyloidplaques. Since the cholinergic system plays an importantrole in the regulation of learning and memory processes, ithas been targetted for the design of anti-Alzheimer’s drugs.
Cholinesterase inhibitors enhance cholinergic transmissiondirectly by inhibiting the enzyme acetylcholinesterase(AChE) which hydrolyses acetylcholine. Furthermore, ithas been also demonstrated that both acetylcholinesteraseand butrylcholinesterase (BuChE) play an important role inAb-aggregation during the early stages of senile plaqueformation. Therefore, AChE and BuChE inhibition havebeen documented as critical targets for the effectivemanagement of AD by an increase in the availability ofacetylcholine in the brain regions and decrease in the Abdeposition. This review discusses the different classes ofcholinesterase inhibitors including tacrine, donepezil,rivastigmine, galantamine, xanthostigmine, para-aminobenzoicacid, coumarin, flavonoid, and pyrrolo-isoxazoleanalogues developed for the treatment of AD.

참고문헌 (Reference)

• 1 Musial, A., 77-, 2006
• 2 Correa-Basurto, J., "p-Aminobenzoic acid derivatives as acetylcholinesterase inhibitors" 40 : 732-735, 2005
• 3 Mao, F., "o-Hydroxyl-or o-amino benzylamine-tacrine hybrids : Multifunctional biometals chelators, antioxidants, and inhibitors of cholinesterase activity and amyloid-b aggregation" 20 : 5884-5892, 2012
• 4 Bartolini, M., "beta-Amyloid aggregation induced by human acetylcholinesterase : Inhibition studies" 65 : 407-416, 2003
• 5 Harvey, A. L, "The pharmacology of galanthamine and its analogues" 68 : 113-128, 1995
• 6 Liu, J., "The nitric oxide donor, O2-vinyl 1-(pyrrolidin-1-l)diazen-1-ium-1, 2-diolate(V-PYRRO/NO), protects against cadmium-induced hepatotoxicity in mice" 310 : 18-24, 2004
• 7 Masilamoni, J. G., "The neuroprotective role of melatonin against amyloid beta peptide injected mice" 42 : 661-673, 2008
• 8 Radic´, Z., "The influence of peripheral site ligands on the reaction of symmetric and chiral organophosphates with wildtype and mutant acetylcholinesterases" 119 : 111-117, 1999
• 9 Marco-Contelles, J., "Tacripyrines, the first tacrine-dihydropyridine hybrids, as multitarget-directed ligands for the treatment of Alzheimer’s disease" 52 : 2724-2732, 2009
• 10 Ferna´ndez-Bachiller, M. I., "Tacrine-melatonin hybrids as multifunctional agents for Alzheimer’s disease, with cholinergic, antioxidant, and neuroprotective properties" 4 : 828-841, 2009
• 11 Winker, M. A, "Tacrine for Alzheimer’s disease. Which patient, what dose?" 271 : 1023-1024, 1994
• 12 Kato, K., "TAK-147, an acetylcholinesterase inhibitor, increases choline acetyltransferase activity in cultured rat septal cholinergic neurons" 260 : 5-8, 1999
• 13 Hamulakova, S., "Synthesis, design and biological evaluation of novel highly potent tacrine congeners for the treatment of Alzheimer’s disease" 55 : 23-31, 2012
• 14 Marco, J. L., "Synthesis, biological evaluation and molecular modelling of diversely functionalized heterocyclic derivatives as inhibitors of acetylcholinesterase/butyrylcholinesterase and modulators of Ca2? channels and nicotinic receptors" 12 : 2199-2218, 2004
• 15 Trujillo-Ferrara, J., "Synthesis, anticholinesterase activity and structure-activity relationships of m-Aminobenzoic acid derivatives" 13 : 1825-1827, 2003
• 16 Leo´n, R., "Synthesis, acetylcholinesterase inhibition and neuroprotective activity of new tacrine analogues" 13 : 1167-1175, 2005
• 17 Ismail, M. M., "Synthesis of new indole derivatives structurally related to donepezil and their biological evaluation as acetylcholinesterase inhibitors" 17 : 4811-4823, 2012
• 18 Herlem, D., "Synthesis and structure-activity relationships of open D-Ring galanthamine analogues" 13 : 2389-2391, 2003
• 19 Andreani, A., "Synthesis and screening for antiacetylcholinesterase activity of(1-benzyl-4-oxopiperidin-3-ylidene)methylindoles and-pyrroles related to donepezil" 44 : 4011-4014, 2001
• 20 Shao, D., "Synthesis and evaluation of tacrine-E2020 hybrids as acetylcholinesterase inhibitors for the treatment of Alzheimer’s disease" 14 : 4639-4642, 2004
• 21 Anand, P., "Synthesis and evaluation of novel carbamate substituted flavanone derivatives as potent acetylcholinesterase inhibitors and anti-amnestic agents" 2012
• 22 Anand, P., "Synthesis and evaluation of novel 4-[(3H, 3aH, 6aH)-3-phenyl)-4, 6-dioxo-2-phenyldihydro-2H-pyrrolo[ 3, 4-d]isoxazol-(3H, 6H, 6aH)-yl]benzoic acid derivatives as potent acetylcholinesterase inhibitors and anti-amnestic agents" 20 : 521-530, 2012
• 23 Mustazza, C., "Synthesis and cholinesterase activity of phenylcarbamates related to Rivastigmine, a therapeutic agent for Alzheimer’s disease" 37 : 91-109, 2002
• 24 Ismail, M. M., "Synthesis and biological evaluation of thiophene derivatives as acetylcholinesterase inhibitors" 17 : 7217-7231, 2012
• 25 Shen, Y., "Synthesis and biological evaluation of novel flavonoid derivatives as dual binding acetylcholinesterase inhibitors" 24 : 372-380, 2009
• 26 Shen, Q., "Synthesis and biological evaluation of functionalized coumarins as acetylcholinesterase inhibitors" 40 : 1307-1315, 2005
• 27 Marco, J. L., "Synthesis and acetylcholinesterase/ butyrylcholinesterase inhibition activity of new tacrine-like analogues" 9 : 727-732, 2001
• 28 Sippl, W., "Structure-based 3D QSAR and design of novel acetylcholinesterase inhibitors" 15 : 395-410, 2001
• 29 Kryger, G., "Structure of acetylcholinesterase complexed with E2020(Aricept) : Implications for the design of new anti-Alzheimer drugs" 7 : 297-307, 1999
• 30 Bourne, Y., "Structural insights into ligand interactions at the acetylcholinesterase peripheral anionic site" 22 : 1-12, 2003
• 31 Katalinic´, M., "Structural aspects of flavonoids as inhibitors of human butyrylcholinesterase" 45 : 186-192, 2010
• 32 Thomsen, T., "Stereoselectivity of cholinesterase inhibition by galanthamine and tolerance in humans" 39 : 603-605, 1990
• 33 Savini, L., "Specific targeting of acetylcholinesterase and butyrylcholinesterase recognition sites. Rational design of novel, selective, and highly potent cholinesterase inhibitors" 46 : 1-4, 2003
• 34 Thomsen, T., "Selective inhibition of human acetylcholinesterase by galanthamine in vitro and in vivo" 46 : 1553-1558, 1990
• 35 Gottwald, M. D., "Rivastigmine, a brainregion selective acetylcholinesterase inhibitor for treating Alzheimer’s disease : Review and current status" 8 : 1673-1682, 1999
• 36 Trujillo-Ferrara, J., "Reversible and irreversible inhibitory activity of succinic and maleic acid derivatives on acetylcholinesterase" 18 : 313-322, 2003
• 37 Chen, Z., "Reversal of scopolamine-induced spatial memory deficits in rats by TAK-147" 23 : 355-360, 2002
• 38 Rosini, M., "Rational approach to discover multipotent anti-Alzheimer drugs" 48 : 360-363, 2005
• 39 Heilmann, J., "Radical scavenger activity of phenylethanoid glycosides in FMLP stimulated human polymorphonuclear leukocytes : Structure-activity relationships" 66 : 746-748, 2000
• 40 Richetti, S. K., "Quercetin and rutin prevent scopolamine-induced memory impairment in zebrafish" 217 : 10-15, 2011
• 41 Harel, M., "Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase" 90 : 9031-9035, 1993
• 42 Wu, C. R., "Psoralen and isopsoralen, two coumarins of Psoraleae Fructus, can alleviate scopolamine-induced amnesia in rats" 73 : 275-278, 2007
• 43 Yan, J. J., "Protection against betaamyloid peptide toxicity in vivo with long-term administration of ferulic acid" 133 : 89-96, 2001
• 44 Bolognesi, M. L., "Propidium-based polyamine ligands as potent inhibitors of acetylcholinesterase and acetylcholinesteraseinduced amyloid-beta aggregation" 48 : 24-27, 2005
• 45 Guillou, C., "Potent acetylcholinesterase inhibitors : design, synthesis and structureactivity relationships of alkylene linked bis-galanthamine and galanthamine-galanthaminium salts" 10 : 637-639, 2000
• 46 Mary, A., "Potent acetylcholinesterase inhibitors : Design, synthesis, and structureactivity relationships of bis-interacting ligands in the galanthamine series" 6 : 1835-1850, 1998
• 47 Ladner, C. J., "Pharmacological drug treatment of Alzheimer disease : The cholinergic hypothesis revisited" 57 : 719-731, 1998
• 48 Radic´, Z., "Peripheral site ligands accelerate inhibition of acetylcholinesterase by neutral organophosphates" 21 (21): 13-14, 2001
• 49 Castro, A., "Peripheral and dual binding site acetylcholinesterase inhibitors : Implications in treatment of Alzheimer’s disease" 1 : 267-272, 2001
• 50 Zafrilla, P., "Oxidative stress in Alzheimer patients in different stages of the disease" 13 : 1075-1083, 2006
• 51 Rodrı´guez-Franco, M. I., "Novel tacrine-melatonin hybrids as dual-acting drugs for Alzheimer disease, with improved acetylcholinesterase inhibitory and antioxidant properties" 49 : 459-462, 2006
• 52 Marco-Contelles, J., "Novel multipotent tacrine-dihydropyridine hybrids with improved acetylcholinesterase inhibitory and neuroprotective activities as potential drugs for the treatment of Alzheimer’s disease" 49 : 7607-7610, 2006
• 53 Sterling, J., "Novel dual inhibitors of AChE and MAO derived from hydroxy aminoindan and phenethylamine as potential treatment for Alzheimer’s disease" 45 : 5260-5279, 2002
• 54 Camps, P., "Novel donepezil-based inhibitors of acetyl-and butyrylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation" 51 : 3588-3598, 2008
• 55 Villalobos, A., "Novel benzisoxazole derivatives as potent and selective inhibitors of acetylcholinesterase" 37 : 2721-2734, 1994
• 56 Savini, L., "Novel and potent tacrine-related hetero-and homobivalent ligands for acetylcholinesterase and butyrylcholinesterase" 11 : 1779-1782, 2001
• 57 Vidaluc, J. L., "Novel [2-(4-piperidinyl)ethyl](thio)ureas : Synthesis and antiacetylcholinesterase activity" 37 : 689-695, 1994
• 58 Thatcher, G. R., "Nitric oxide mimetic molecules as therapeutic agents in Alzheimer’s disease" 2 : 171-182, 2005
• 59 Malinski, T, "Nitric oxide and nitroxidative stress in Alzheimer’s disease" 11 : 207-218, 2007
• 60 Leo´n, R., "New tacrine-dihydropyridine hybrids that inhibit acetylcholinesterase, calcium entry, and exhibit neuroprotection properties" 16 : 7759-7769, 2008
• 61 Martinez, A., "N-Benzylpiperidine derivatives of 1, 2, 4-thiadiazolidinone as new acetylcholinesterase inhibitors" 35 : 913-922, 2000
• 62 Petroianu, G., "Multiple enzyme inhibitions by histamine H3 receptor antagonists as potential procognitive agents" 61 : 179-182, 2006
• 63 Piazzi, L., "Multi-targetdirected coumarin derivatives : hAChE and BACE1 inhibitors as potential anti-Alzheimer compounds" 18 : 423-426, 2008
• 64 Lin, G., "Molecular recognition by acetylcholinesterase at the peripheral anionic site : Structureactivity relationships for inhibitions by aryl carbamates" 7 : 2683-2689, 1999
• 65 Acuna-Castroviejo, D., "Melatonin role in the mitochondrial function" 12 : 947-963, 2007
• 66 Bachurin, S. O, "Medicinal chemistry approaches for the treatment and prevention of Alzheimer’s disease" 23 : 48-88, 2003
• 67 Holmquist, L., "Lipoic acid as a novel treatment for Alzheimer’s disease and related dementias" 113 : 154-164, 2007
• 68 Kim, J. Y., "Isolation of cholinesterase-inhibiting flavonoids from Morus lhou" 59 : 4589-4596, 2011
• 69 Huang, L., "Inhibition of cholinesterase activity and amyloid aggregation by berberine-phenyl-benzoheterocyclic and tacrine-phenyl-benzoheterocyclic hybrids" 20 : 3038-3048, 2012
• 70 Rosini, M., "Inhibition of acetylcholinesterase, betaamyloid aggregation, and NMDA receptors in Alzheimer’s disease : A promising direction for the multi-target-directed ligands gold rush" 51 : 4381-4384, 2008
• 71 Fallarero, A., "Inhibition of acetylcholinesterase by coumarins : The case of coumarin 106" 58 : 215-221, 2008
• 72 Leonetti, F., "Homo-and hetero-bivalent edrophonium-like ammonium salts as highly potent, dual binding site AChE inhibitors" 16 : 7450-7456, 2008
• 73 Pang, Y. P., "Highly potent, selective, and low cost bis-tetrahydroaminacrine inhibitors of acetylcholinesterase. Steps toward novel drugs for treating Alzheimer’s disease" 271 : 23646-23649, 1996
• 74 Watkins, P. B., "Hepatotoxic effects of tacrine administration in patients with Alzheimer’s disease" 271 : 992-998, 1994
• 75 Cappelli, A., "Further studies on the interaction of the 5-hydroxytryptamine3(5-HT3)receptor with arylpiperazine ligands. Development of a new 5-HT3 receptor ligand showing potent acetylcholinesterase inhibitory properties" 48 : 3564-3575, 2005
• 76 Piazzi, L., "Extensive SAR and computational studies of 3-{4-[(benzylmethylamino)methyl]phenyl}-6, 7-dimethoxy-2H-2-chromenone(AP2238)derivatives" 50 : 4250-4254, 2007
• 77 Nagabukuro, H., "Effects of TAK-802, a novel acetylcholinesterase inhibitor, and various cholinomimetics on the urodynamic characteristics in anesthetized guinea pigs" 494 : 225-232, 2004
• 78 Alonso, D., "Donepezil-tacrine hybrid related derivatives as new dual binding site inhibitors of AChE" 13 : 6588-6597, 2005
• 79 Campiani, G., "Development of molecular probes for the identification of extra interaction sites in the midgorge and peripheral sites of butyrylcholinesterase(BuChE). Rational design of novel, selective, and highly potent BuChE inhibitors" 48 : 1919-1929, 2005
• 80 Contreras, J. M., "Design, synthesis, and structure-activity relationships of a series of 3-[2-(1-benzylpiperidin-4-yl)ethylamino]pyridazine derivatives as acetylcholinesterase inhibitors" 44 : 2707-2718, 2001
• 81 Barreiro, E. J., "Design, synthesis, and pharmacological profile of novel fused pyrazolo[4, 3-d]pyridine and pyrazolo[3, 4-b][1, 8]naphthyridine isosteres : A new class of potent and selective acetylcholinesterase inhibitors" 46 : 1144-1152, 2003
• 82 Meng, F. C., "Design, synthesis, and evaluation of indanone derivatives as acetylcholinesterase inhibitors and metal-chelating agents" 22 : 4462-4466, 2012
• 83 Sheng, R., "Design, synthesis, and evaluation of 2-phenoxy-indan-1-one derivatives as acetylcholinesterase inhibitors" 15 : 3834-3837, 2005
• 84 Mun˜oz-Ruiz, P., "Design, synthesis, and biological evaluation of dual binding site acetylcholinesterase inhibitors : New disease-modifying agents for Alzheimer’s disease" 48 : 7223-7233, 2005
• 85 Pisani, L., "Design, synthesis, and biological evaluation of coumarin derivatives tethered to an edrophonium-like fragment as highly potent and selective dual binding site acetylcholinesterase inhibitors" 5 : 1616-1630, 2010
• 86 Bolognesi, M. L., "Design, synthesis, and biological evaluation of conformationally restricted rivastigmine analogues" 47 : 5945-5952, 2004
• 87 Zhou, X., "Design, synthesis, and acetylcholinesterase inhibitory activity of novel coumarin analogues" 16 : 8011-8021, 2008
• 88 Jia, P., "Design, synthesis and evaluation of galanthamine derivatives as acetylcholinesterase inhibitors" 44 : 772-784, 2009
• 89 Sheng, R., "Design, synthesis and evaluation of flavonoid derivatives as potent AChE inhibitors" 17 : 6692-6698, 2009
• 90 Fang, L., "Design and synthesis of tacrine-ferulic acid hybrids as multi-potent anti-Alzheimer drug candidates" 18 : 2905-2909, 2008
• 91 Selkoe, D. J, "Deciphering the genesis and fate of amyloid betaprotein yields novel therapies for Alzheimer disease" 110 : 1375-1381, 2002
• 92 Bru¨hlmann, C., "Coumarins derivatives as dual inhibitors of acetylcholinesterase and monoamine oxidase" 44 : 3195-3198, 2001
• 93 Howlett, D. R., "Common structural features determine the effectiveness of carvedilol, daunomycin and rolitetracycline as inhibitors of Alzheimer beta-amyloid fibril formation" 343 (343): 419-423, 1999
• 94 Sobrado, M., "Combined nimodipine and citicoline reduce infarct size, attenuate apoptosis and increase bcl-2 expression after focal cerebral ischemia" 118 : 107-113, 2003
• 95 Belluti, F., "Cholinesterase inhibitors : Xanthostigmine derivatives blocking the acetylcholinesterase-induced beta-amyloid aggregation" 48 : 4444-4456, 2005
• 96 Piazzi, L., "Cholinesterase inhibitors : SAR and enzyme inhibitory activity of 3-[omega-(benzylmethylamino)alkoxy]xanthen-9-ones" 15 : 575-585, 2007
• 97 Geula, C., "Butyrylcholinesterase, cholinergic neurotransmission and the pathology of Alzheimer’s disease" 40 : 711-721, 2004
• 98 Colombres, M., "An overview of the current and novel drugs for Alzheimer’s disease with particular reference to anti-cholinesterase compounds" 10 : 3121-3130, 2004
• 99 Contreras, J. M., "Aminopyridazines as acetylcholinesterase inhibitors" 42 : 730-741, 1999
• 100 Rees, T., "Acetylcholinesterase promotes beta-amyloid plaques in cerebral cortex" 24 : 777-787, 2003
• 101 Melchiorre, C., "Acetylcholinesterase noncovalent inhibitors based on a polyamine backbone for potential use against Alzheimer’s disease" 41 : 4186-4189, 1998
• 102 Mesulam, M. M., "Acetylcholinesterase knockouts establish central cholinergic pathways and can use butyrylcholinesterase to hydrolyze acetylcholine" 110 : 627-639, 2002
• 103 Jung, M., "Acetylcholinesterase inhibition by flavonoids from Agrimonia pilosa" 12 : 2130-2139, 2007
• 104 Changwong, N., "Acetyl-and butyryl-cholinesterase inhibitory activities of mansorins and mansonones" 26 : 392-396, 2012
• 105 De Ferrari, G. V., "A structural motif of acetylcholinesterase that promotes amyloid beta-peptide fibril formation" 40 : 10447-10457, 2001
• 106 Lin, G., "A rate determining step change in the pre-steady state of acetylcholinesterase inhibitions by 1, n-alkane-di-N-butylcarbamates" 15 : 951-955, 2005
• 107 Tomas-Zapico, C., "A proposed mechanism to explain the stimulatory effect of melatonin on antioxidative enzymes" 39 : 99-104, 2005
• 108 Toda, N., "A conformational restriction approach to the development of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer’s disease" 11 : 4389-4415, 2003
• 109 Knapp, M. J., "A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer’s disease. The Tacrine Study Group" 271 : 985-991, 1994
• 110 Schalk, I., "6-Coumarin diazonium salt : a specific affinity label of the Torpedo acetylcholinesterase peripheral site" 48 : 1063-1067, 1995
• 111 Villalobos, A., "5, 7-dihydro-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-6H-pyrrolo[ 3, 2-f]-1, 2 benzisoxazol-6-one : a potent and centrally-selective inhibitor of acetylcholinesterase with an improved margin of safety" 38 : 2802-2808, 1995
• 112 Piazzi, L., "3-(4-[[Benzyl(methyl)amino]methyl]phenyl)-6, 7-dimethoxy-2H-2-chromenone(AP2238)inhibits both acetylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation : A dual function lead for Alzheimer’s disease therapy" 46 : 2279-2282, 2003
• 113 Ucar, G., "1-NSubstituted thiocarbamoyl-3-phenyl-5-thienyl-2-pyrazolines : A novel cholinesterase and selective monoamine oxidase B inhibitors for the treatment of Parkinson’s and Alzheimer’s diseases" 382 : 327-331, 2005