Synthesis, molecular modelling and biological evaluation of novel heterodimeric, multiple ligands targeting cholinesterases and amyloid Beta

Molecules

Volumn 21, Issue 4, 2016, Pages

  Hebda, Michalina ^a   Bajda, Marek ^a   Wieckowska, Anna ^a   Szalłaj, Natalia ^a   Pasieka, Anna ^a   Panek, Dawid ^a   Godyń, Justyna ^a   Wichur, Tomasz ^a   Knez, Damijan ^b   Gobec, Stanislav ^b   Malawska, Barbara ^a  

^a JAGIELLONIAN UNIVERSITY MEDICAL COLLEGE   (Poland)

^b UNIVERSITY OF LJUBLJANA   (Slovenia)

Author keywords

Alzheimer's disease; Cholinesterase inhibitors; Molecular modelling; Multi target directed ligands (mtdl); Pampa bbb assay; amyloid aggregation inhibitors

Indexed keywords

ACETYLCHOLINESTERASE; AMYLOID BETA PROTEIN; CHOLINESTERASE; CHOLINESTERASE INHIBITOR; ISOINDOL-1-ONE; ISOINDOLE DERIVATIVE; LIGAND;

ALZHEIMER DISEASE; BINDING SITE; BLOOD BRAIN BARRIER; CHEMISTRY; DRUG EFFECTS; HUMAN; METABOLISM; MOLECULAR MODEL; PATHOLOGY; PROTEIN AGGREGATION, PATHOLOGICAL; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ACETYLCHOLINESTERASE; ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; BINDING SITES; BLOOD-BRAIN BARRIER; BUTYRYLCHOLINESTERASE; CHOLINESTERASE INHIBITORS; HUMANS; ISOINDOLES; LIGANDS; MODELS, MOLECULAR; PROTEIN AGGREGATION, PATHOLOGICAL; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84969136061     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules21040410     Document Type: Article

References (65)

1. Prince, M.; Prina, M.; Guerchet, M. World Alzheimer Report 2013 Journey of Caring: An Analysis of Long-Term Care for Dementia; Alzheimer's Disease International: London, UK, 2013; pp. 1-92.
2. Wimo, A.; Jönsson, L.; Bond, J.; Prince, M.; Winblad, B. The worldwide economic impact of dementia 2010. Alzheimer's Dement. 2013, 9.
3. Cummings, J.L.; Morstorf, T.; Zhong, K. Alzheimer's disease drug-development pipeline: Few candidates, frequent failures. Alzheimers. Res. Ther. 2014, 6.
4. Godyń, J.; Jończyk, J.; Panek, D.; Malawska, B. Therapeutic strategies for Alzheimer's disease in clinical trials. Pharmacol. Rep. 2015, 68, 127-138.
5. Blennow, K.; de Leon, M.J.; Zetterberg, H. Alzheimer's disease. Lancet 2006, 368, 387-403.
6. Querfurth, H.W.; LaFerla, F.M. Alzheimer's disease. N. Engl. J. Med. 2010, 362, 329-344.
7. Bowen, D.M.; Smith, C.B.; White, P.; Davison, A.N. Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies. Brain 1976, 99, 459-496.
8. Davies, P.; Maloney, A.J.F. Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 1976, 308.
9. Mufson, E.J.; Counts, S.E.; Perez, S.E.; Ginsberg, S.D. Cholinergic system during the progression of Alzheimer's disease: Therapeutic implications. Expert Rev. Neurother. 2008, 8, 1703-1718.
10. Giacobini, E. Cholinesterase inhibitors: New roles and therapeutic alternatives. Pharmacol. Res. 2004, 50, 433-440.
11. De Ferrari, G.V.; Canales, M.A.; Shin, I.; Weiner, L.M.; Silman, I.; Inestrosa, N.C. A Structural Motif of Acetylcholinesterase That Promotes Amyloid β-Peptide Fibril Formation. Biochemistry 2001, 40, 10447-10457.
12. Johnson, G.; Moore, S.W. Identification of a structural site on acetylcholinesterase that promotes neurite outgrowth and binds laminin-1 and collagen IV. Biochem. Biophys. Res. Commun. 2004, 319, 448-455.
13. 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, 881-891.
14. Sussman, J.L.; Harel, M.; Frolow, F.; Oefner, C.; Goldman, A.; Toker, L.; Silman, I. Atomic structure of acetylcholinesterase from Torpedo californica: A prototypic acetylcholine-binding protein. Science 1991, 253, 872-879.
15. Akasofu, S.; Kimura, M.; Kosasa, T.; Sawada, K.; Ogura, H. Study of neuroprotection of donepezil, a therapy for Alzheimer's disease. Chem. Biol. Interact. 2008, 175, 222-226.
16. Akaike, A.; Takada-Takatori, Y.; Kume, T.; Izumi, Y. Mechanisms of Neuroprotective Effects of Nicotine and Acetylcholinesterase Inhibitors: Role of α4 and α7 Receptors in Neuroprotection. J. Mol. Neurosci. 2009, 40, 211-216.
17. Verdile, G.; Fuller, S.J.; Martins, R.N. The role of type 2 diabetes in neurodegeneration. Neurobiol. Dis. 2015, 84, 22-38.
18. Zhao, Y.; Zhao, B. Oxidative stress and the pathogenesis of Alzheimer's disease. Oxid. Med. Cell. Longev. 2013, 2013.
19. Kan, M.J.; Lee, J.E.; Wilson, J.G.; Everhart, A.L.; Brown, C.M.; Hoofnagle, A.N.; Jansen, M.; Vitek, M.P.; Gunn, M.D.; Colton, C.A. Arginine Deprivation and Immune Suppression in a Mouse Model of Alzheimer's Disease. J. Neurosci. 2015, 35, 5969-5982.
20. Morphy, R.; Kay, C.; Rankovic, Z. From magic bullets to designed multiple ligands. Drug Discov. Today 2004, 9, 641-651.
21. Zimmermann, G.R.; Lehár, J.; Keith, C.T. Multi-target therapeutics: When the whole is greater than the sum of the parts. Drug Discov. Today 2007, 12, 34-42.
22. Guzior, N.; Ckowska, 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, 373-404.
23. Dias, K.S.T.; Viegas, C., Jr. Multi-Target Directed Drugs: A Modern Approach for Design of New Drugs for the treatment of Alzheimer's Disease. Curr. Neuropharmacol. 2014, 12, 239-255.
24. Agis-Torres, A.; Sölhuber, M.; Fernandez, M.; Sanchez-Montero, J.M. Multi-Target-Directed Ligands and other Therapeutic Strategies in the Search of a Real Solution for Alzheimer's Disease. Curr. Neuropharmacol. 2014, 12, 2-36.
25. Calza, L.; Antonio Baldassarro, V.; Giuliani, A.; Lorenzini, L.; Fernandez, M.; Mangano, C.; Sivilia, S.; Alessandri, M.; Gusciglio, M.; Torricella, R.; et al. From the Multifactorial Nature of Alzheimer's Disease to Multitarget Therapy: The Contribution of the Translational Approach. Curr. Top. Med. Chem. 2013, 13, 1843-1852.
26. Carreiras, M.; Mendes, E.; Perry, M.; Francisco, A.; Marco-Contelles, J. The Multifactorial Nature of Alzheimer's Disease for Developing Potential Therapeutics. Curr. Top. Med. Chem. 2013, 13, 1745-1770.
27. León, R.; Garcia, A.G.; Marco-Contelles, J. Recent advances in the multitarget-directed ligands approach for the treatment of Alzheimer's disease. Med. Res. Rev. 2013, 33, 139-189.
28. Sola, I.; Aso, E.; Frattini, D.; López-González, I.; Espargaró, A.; Sabaté, R.; Di Pietro, O.; Luque, F.J.; Clos, M.V.; Ferrer, I.; et al. Novel Levetiracetam Derivatives That Are Effective against the Alzheimer-like Phenotype in Mice: Synthesis, in Vitro, ex Vivo, and in Vivo Efficacy Studies. J. Med. Chem. 2015, 58, 6018-6032.
29. Knez, D.; Brus, B.; Coquelle, N.; Sosiě, I.; Šink, R.; Brazzolotto, X.; Mravljak, J.; Colletier, J.P.; Gobec, S. Structure-based development of nitroxoline derivatives as potential multifunctional anti-Alzheimer agents. Bioorg. Med. Chem. 2015, 23.
30. Tonelli, M.; Catto, M.; Tasso, B.; Novelli, F.; Canu, C.; Iusco, G.; Pisani, L.; de Stradis, A.; Denora, N.; Sparatore, A.; et al. Multitarget Therapeutic Leads for Alzheimer's Disease: Quinolizidinyl Derivatives of Biand Tricyclic Systems as Dual Inhibitors of Cholinesterases and β-Amyloid (Aβ) Aggregation. ChemMedChem 2015, 10, 1040-1053.
31. Farina, R.; Pisani, L.; Catto, M.; Nicolotti, O.; Gadaleta, D.; Denora, N.; Soto-Otero, R.; Mendez-Alvarez, E.; Passos, C.S.; Muncipinto, G.; et al. Structure-Based Design and Optimization of Multitarget-Directed 2 H -Chromen-2-one Derivatives as Potent Inhibitors of Monoamine Oxidase B and Cholinesterases. J. Med. Chem. 2015, 58, 5561-5578.
32. Xie, S.S.; Wang, X.; Jiang, N.; Yu, W.; Wang, K.D.G.; 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.
33. Bolea, I.; Juárez-Jiménez, J.; de los Ríos, C.; Chioua, M.; Pouplana, R.; Luque, F.J.; Unzeta, M.; Marco-Contelles, J.; Samadi, A. Synthesis, Biological Evaluation, and Molecular Modeling of Donepezil and N-[(5-(Benzyloxy)-1-methyl-1H-indol-2-yl)methyl]-N-methylprop-2-yn-1-amine Hybrids as New Multipotent Cholinesterase/Monoamine Oxidase Inhibitors for the Treatment of Alzheimer's Disease. J. Med. Chem. 2011, 54, 8251-8270.
34. Pau, A.; Catto, M.; Pinna, G.; Frau, S.; Murineddu, G.; Asproni, B.; Curzu, M.M.; Pisani, L.; Leonetti, F.; Loza, M.I.; et al. Multitarget-directed tricyclic pyridazinones as G protein-coupled receptor ligands and cholinesterase inhibitors. ChemMedChem 2015, 10, 1054-1070.
35. Rochais, C.; Lecoutey, C.; Gaven, F.; Giannoni, P.; Hamidouche, K.; Hedou, D.; Dubost, E.; Genest, D.; Yahiaoui, S.; Freret, T.; et al. Novel Multitarget-Directed Ligands (MTDLs) with Acetylcholinesterase (AChE) Inhibitory and Serotonergic Subtype 4 Receptor (5-HT4 R) Agonist Activities As Potential Agents against Alzheimer's Disease: The Design of Donecopride. J. Med. Chem. 2015, 58, 3172-3187.
36. Xie, S.S.; Lan, J.S.; Wang, X.B.; Jiang, N.; Dong, G.; Li, Z.R.; Wang, K.D.G.; Guo, P.P.; Kong, L.Y. Multifunctional tacrine-trolox hybrids for the treatment of Alzheimer's disease with cholinergic, antioxidant, neuroprotective and hepatoprotective properties. Eur. J. Med. Chem. 2015, 93, 42-50.
37. Ignasik, M.; Bajda, M.; Guzior, N.; Prinz, M.; Holzgrabe, U.; Malawska, B. Design, synthesis and evaluation of novel 2-(aminoalkyl)-isoindoline-1,3-dione derivatives as dual-binding site acetylcholinesterase inhibitors. Arch. Pharm. 2012, 345, 509-516.
38. Guzior, N.; Bajda, M.; Skrok, M.; Kurpiewska, K.; Lewiński, K.; Brus, B.; Pišlar, A.; Kos, J.; Gobec, S.; Malawska, B. Development of multifunctional, heterodimeric isoindoline-1,3-dione derivatives as cholinesterase and β-amyloid aggregation inhibitors with neuroprotective properties. Eur. J. Med. Chem. 2015, 92, 738-749.
39. Guzior, N.; Bajda, M.; Rakoczy, J.; Brus, B.; Gobec, S.; Malawska, B. Isoindoline-1,3-dione derivatives targeting cholinesterases: Design, synthesis and biological evaluation of potential anti-Alzheimer's agents. Bioorg. Med. Chem. 2015, 23, 1629-1637.
40. Szalłaj, N.; Bajda, M.; Dudek, K.; Brus, B.; Gobec, S.; Malawska, B. Multiple Ligands Targeting Cholinesterases and b-Amyloid: Synthesis, Biological Evaluation of Heterodimeric Compounds with Benzylamine Pharmacophore. Arch. Pharm. Chem. Life Sci. 2015, 348, 556-563.
41. Ckowska, A.; Ckowski, K.; Bajda, M.; Brus, B.; Salłat, K.; Czerwiñska, P.; Gobec, S.; Filipek, B.; Malawska, B. Synthesis of new N-benzylpiperidine derivatives as cholinesterase inhibitors with β-amyloid anti-aggregation properties and beneficial effects on memory in vivo. Bioorg. Med. Chem. 2015, 23, 2445-2457.
42. Ellman, G.L.; Courtney, K.D.; Andres, V.; Featherstone, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 1961, 7, 88-95.
43. Cornish-Bowden, A. A simple graphical method for determining the inhibition constants of mixed, uncompetitive and non-competitive inhibitors. Biochem. J. 1974, 137, 143-144.
44. Faller, P.; Hureau, C.; Berthoumieu, O. Role of metal ions in the self-assembly of the Alzheimer's amyloid-β peptide. Inorg. Chem. 2013, 52, 12193-12206.
45. Inestrosa, N.C.; Dinamarca, M.C.; Alvarez, A. Amyloid-cholinesterase interactions. Implications for Alzheimer's disease. FEBS J. 2008, 275, 625-632.
46. Huang, L.; Liu, X.; Cheng, B.; Huang, K. How our bodies fight amyloidosis: Effects of physiological factors on pathogenic aggregation of amyloidogenic proteins. Arch. Biochem. Biophys. 2015, 568, 46-55.
47. LeVine, H. Biotin-avidin interaction-based screening assay for Alzheimer's beta-peptide oligomer inhibitors. Anal. Biochem. 2006, 356, 265-272.
48. Bajda, M.; Ckowska, A.; Hebda, M.; Guzior, N.; Sotriffer, C.A.; Malawska, B. Structure-based search for new inhibitors of cholinesterases. Int. J. Mol. Sci. 2013, 14, 5608-5632.
49. Sopkova-de Oliveira Santos, J.; Lesnard, A.; Agondanou, J.-H.; Dupont, N.; Godard, A.-M.; Stiebing, S.; Rochais, C.; Fabis, F.; Dallemagne, P.; Bureau, R.; et al. Virtual Screening Discovery of New Acetylcholinesterase Inhibitors Issued from CERMN Chemical Library. J. Chem. Inf. Model. 2010, 50, 422-428.
50. Di, L.; Kerns, E.H.; Fan, K.; McConnell, O.J.; Carter, G.T. High throughput artificial membrane permeability assay for blood-brain barrier. Eur. J. Med. Chem. 2003, 38, 223-232.
51. Apelt, J.; Ligneau, X.; Pertz, H.H.; Arrang, J.M.; Ganellin, C.R.; Schwartz, J.C.; Schunack, W.; Stark, H. Development of a new class of nonimidazole histamine H3 receptor ligands with combined inhibitory histamine N-methyltransferase activity. J. Med. Chem. 2002, 45, 1128-1141.
52. Fisher, M.J.; Gunn, B.; Harms, C.S.; Kline, A.D.; Mullaney, J.T.; Nunes, A.; Scarborough, R.M.; Arfsten, A.E.; Skelton, M.A.; Um, S.L.; et al. Non-peptide RGD surrogates which mimic a Gly-Asp β-turn: Potent antagonists of platelet glycoprotein IIb-IIIa. J. Med. Chem. 1997, 40, 2085-2101.
53. Dehaen, W.; Hassner, A. Cycloadditions. 45. Annulation of heterocycles via intramolecular nitrile oxide-heterocycle cycloaddition reaction. J. Org. Chem. 1991, 56, 896-900.
54. Plocki, S.; Aoun, D.; Ahamada-Himidi, A.; Tavarès-Camarinha, F.; Dong, C.-Z.; Massicot, F.; Huet, J.; Adolphe-Pierre, S.; Chau, F.; Godfroid, J.-J.; et al. Molecular Modeling, Design, and Synthesis of Less Lipophilic Derivatives of 3-(4-Tetradecyloxybenzyl)-4H-1,2,4-oxadiazol-5-one (PMS1062) Specific for Group II Enzyme. Eur. J. Org. Chem. 2005, 2005, 2747-2757.
55. Choi, J.Y.; Seo, H.N.; Lee, M.J.; Park, S.J.; Park, S.J.; Jeon, J.Y.; Kang, J.H.; Pae, A.N.; Rhim, H.; Lee, J.Y. Synthesis and biological evaluation of novel T-type calcium channel blockers. Bioorg. Med. Chem. Lett. 2007, 17, 471-475.
56. Dickson, J.K. Jr.; Hodge, C.N.; Mendoza, J.S.; Chen, K. 2-Amido-Thiazole-based Compounds Exhibiting ATP-Utilizing Enzyme Inhibitory Activity, and Compositions, and Uses Thereof. U.S. Patent No 7,410,988, 12 August 2008.
57. Alisi, M.A.; Brufani, M.; Cesta, M.C.; Filocamo, L.; Gostoli, G.; Lappa, S.; Pagella, P.G.; Ferrari, E.; Maiorana, S.; Marchesini, D. Mediolanium Farmaceutucu S.P.A. Milan, Italy, Aminoalkylcarbamic Esters of Eseroline Suitable for Use As Chlorinesterase Activity Inhibitors. U.S. Patent No 5,302,593, 12 April 1994.
58. Mokrosz, J.L.; Dereń-Wesolłek, A.; Tatarczyńska, E.; Duszyńska, B.; Bojarski, A.J.; Mokrosz, M.J.; Chojnacka-Wójcik, E. 8-[4-[2-(1,2,3,4-Tetrahydroisoquinolinyl)]butyl]-8-azaspiro[4.5]decane-7,9-dione: A New 5-HT1A Receptor Ligand with the Same Activity Profile as Buspirone. J. Med. Chem. 1996, 39, 1125-1129.
59. Kowalski, P.; Mitka, K.; Jákowska, J.; Duszyńska, B.; Bojarski, A.J. New Arylpiperazines with Flexible versus Partly Constrained Linker as Serotonin 5-HT1A /5-HT7 Receptor Ligands. Arch. Pharm. (Weinheim). 2013, 346, 339-348.
60. Tsotinis, A.; Afroudakis, P.A.; Davidson, K.; Prashar, A.; Sugden, D. Design, Synthesis, and Melatoninergic Activity of New Azido- and Isothiocyanato-Substituted Indoles. J. Med. Chem. 2007, 50, 6436-6440.
61. Contreras, J.M.; Rival, Y.M.; Chayer, S.; Bourguignon, J.J.; Wermuth, C.G. Aminopyridazines as acetylcholinesterase inhibitors. J. Med. Chem. 1999, 42, 730-741.
62. Commerford, J.D.; Donahue, H.B. Notes -N-(-Bromoalkyl)saccharins and N,N'-Undecamethylenedisaccharin. J. Org. Chem. 1956, 21, 583-584.
63. Meng, F.C.; Mao, F.; Shan, W.J.; Qin, F.; Huang, L.; Li, X.S. Design, synthesis, and evaluation of indanone derivatives as acetylcholinesterase inhibitors and metal-chelating agents. Bioorg. Med. Chem. Lett. 2012, 22, 4462-4466.
64. Tasso, B.; Catto, M.; Nicolotti, O.; Novelli, F.; Tonelli, M.; Giangreco, I.; Pisani, L.; Sparatore, A.; Boido, V.; Carotti, A.; et al. Quinolizidinyl derivatives of bi- and tricyclic systems as potent inhibitors of acetyland butyrylcholinesterase with potential in Alzheimer's disease. Eur. J. Med. Chem. 2011, 46, 2170-2184.
65. Shaik, J.B.; Palaka, B.K.; Penumala, M.; Kotapati, K.V.; Devineni, S.R.; Eadlapalli, S.; Darla, M.M.; Ampasala, D.R.; Vadde, R.; Amooru, G.D. Synthesis, pharmacological assessment, molecular modeling and in silico studies of fused tricyclic coumarin derivatives as a new family of multifunctional anti-Alzheimer agents. Eur. J. Med. Chem. 2016, 107, 219-232.