Development of multifunctional, heterodimeric isoindoline-1,3-dione derivatives as cholinesterase and β-amyloid aggregation inhibitors with neuroprotective properties

European Journal of Medicinal Chemistry

Volumn 92, Issue , 2015, Pages 738-749

  Guzior, Natalia ^a   Bajda, Marek ^a   Skrok, Miroslaw ^a   Kurpiewska, Katarzyna ^b   LewiÅski, Krzysztof ^b   Brus, Boris ^c   Pišlar, Anja ^c   Kos, Janko ^c,d   Gobec, Stanislav ^c   Malawska, Barbara ^a  

^a JAGIELLONIAN UNIVERSITY MEDICAL COLLEGE   (Poland)

^b JAGIELLONIAN UNIVERSITY   (Poland)

^c UNIVERSITY OF LJUBLJANA   (Slovenia)

^d JO EF STEFAN INSTITUTE   (Slovenia)

Author keywords

Alzheimer's disease; Cholinesterase inhibitors; Multi target directed ligands; Neuroprotection; amyloid aggregation inhibitors

Indexed keywords

2 [4 (2 FLUOROBENZYLAMINO)BUTYL]ISOINDOLINE 1,3 DIONE; 2 [4 (2,4 DIFLUOROBENZYLAMINO)BUTYL]ISOINDOLINE 1,3 DIONE; 2 [4 (3 CHLOROBENZYLAMINO)BUTYL]ISOINDOLINE 1,3 DIONE; 2 [4 (4 FLUOROBENZYLAMINO)BUTYL]ISOINDOLINE 1,3 DIONE; 2 [4 (BENZYLAMINO)BUTYL]ISOINDOLINE 1,3 DIONE; 2 [5 (2 FLUOROBENZYLAMINO)PENTYL]ISOINDOLINE 1,3 DIONE; 2 [5 (2,4 DIFLUOROBENZYLAMINO)PENTYL]ISOINDOLINE 1,3 DIONE; 2 [5 (3 CHLOROBENZYLAMINO)PENTYL]ISOINDOLINE 1,3 DIONE; 2 [5 (4 FLUOROBENZYLAMINO)PENTYL]ISOINDOLINE 1,3 DIONE; 2 [6 (2 FLUOROBENZYLAMINO)HEXYL]ISOINDOLINE 1,3 DIONE; 2 [6 (2,4 DIFLUOROBENZYLAMINO)HEXYL]ISOINDOLINE 1,3 DIONE; 2 [6 (3 CHLOROBENZYLAMINO)HEXYL]ISOINDOLINE 1,3 DIONE; 2 [6 (4 FLUOROBENZYLAMINO)HEXYL]ISOINDOLINE 1,3 DIONE; 2 [7 (2 FLUOROBENZYLAMINO)HEPTYL]ISOINDOLINE 1,3 DIONE; 2 [7 (2,4 DIFLUOROBENZYLAMINO)HEPTYL]ISOINDOLINE 1,3 DIONE; 2 [7 (3 CHLOROBENZYLAMINO)HEPTYL]ISOINDOLINE 1,3 DIONE; 2 [7 (4 FLUOROBENZYLAMINO)HEPTYL]ISOINDOLINE 1,3 DIONE; 2 [8 (2 FLUOROBENZYLAMINO)OCTYL]ISOINDOLINE 1,3 DIONE; 2 [8 (2,4 DIFLUOROBENZYLAMINO)OCTYL]ISOINDOLINE 1,3 DIONE; 2 [8 (3 CHLOROBENZYLAMINO)OCTYL]ISOINDOLINE 1,3 DIONE; 2 [8 (4 FLUOROBENZYLAMINO)OCTYL]ISOINDOLINE 1,3 DIONE; ACETYLCHOLINESTERASE; CHOLINESTERASE INHIBITOR; DONEPEZIL; HETERODIMER; ISOINDOLE DERIVATIVE; NEUROPROTECTIVE AGENT; PROTEIN INHIBITOR; TACRINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; 2-(5-(3-CHLOROBENZYLAMINO)PENTYL)ISOINDOLINE-1,3-DIONE; 2-(5-(4-FLUOROBENZYLAMINO)PENTYL)ISOINDOLINE-1,3-DIONE; AMYLOID BETA PROTEIN; BENZYLAMINE DERIVATIVE; PHTHALIMIDE DERIVATIVE; PROTEIN AGGREGATE;

ARTICLE; BIOLOGICAL ACTIVITY; CATALYST; CHOLINESTERASE INHIBITION; COLUMN CHROMATOGRAPHY; CONTROLLED STUDY; CRYSTAL STRUCTURE; CYTOTOXICITY; DRUG ACTIVITY; DRUG BINDING SITE; DRUG CONFORMATION; DRUG POTENCY; DRUG SYNTHESIS; ELECTROPHORUS; ENZYME INHIBITION; ENZYME KINETICS; HUMAN; HUMAN CELL; HYDROGEN BOND; IC50; IN VITRO STUDY; MOLECULAR MODEL; NEUROPROTECTION; NONHUMAN; PROTEIN AGGREGATION; STRUCTURE ACTIVITY RELATION; X RAY DIFFRACTION; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; DOSE RESPONSE; DRUG EFFECTS; METABOLISM; PROTEIN AGGREGATION, PATHOLOGICAL; SYNTHESIS; TUMOR CELL LINE;

ACETYLCHOLINESTERASE; AMYLOID BETA-PEPTIDES; BENZYLAMINES; CELL LINE, TUMOR; CHOLINESTERASE INHIBITORS; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; NEUROPROTECTIVE AGENTS; PHTHALIMIDES; PROTEIN AGGREGATES; PROTEIN AGGREGATION, PATHOLOGICAL; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84921689816     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2015.01.027     Document Type: Article

References (71)

1. D.J. Selkoe Alzheimer disease: mechanistic understanding predicts novel therapies Ann. Intern. Med. 140 2004 627 638
2. S. Salloway S. Correia Alzheimer disease: time to improve its diagnosis and treatment Cleve. Clin. J. Med. 76 2009 49 58
3. H.W. Querfurth F.M. La Ferla Alzheimer's disease N. Engl. J. Med. 362 2010 329 344
4. E. Żerovnik Protein conformational pathology in Alzheimer's and other neurodegenerative diseases; new targets for therapy Curr. Alzh. Res. 7 2010 74 83
5. P. Davies J.F. Maloney Selective loss of central cholinergic neurons in Alzheimer's disease Lancet 308 1976 1403
6. J. Hardy D. Allsop Amyloid deposition as the central event in the aetiology of Alzheimer's disease Trends Pharmacol. Sci. 12 1991 383 388
7. J. Hardy D.J. Selkoe The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics Science 297 2002 353 356
8. M.J. Berridge Calcium hypothesis of Alzheimer's disease Eur. J. Physiol. 459 2010 441 449
9. C.J. Maynard A.I. Bush C.L. Masters R. Cappai Q.X. Li Metals and amyloid-beta in Alzheimer's disease Int. J. Exp. Pathol. 86 2005 147 159
10. Y. Ke Z. Ming Qian Iron misregulation in the brain: a primary cause of neurodegenerative disorders Lancet Neurol. 2 2003 246 253
11. R.J. Van Marum Current and future therapy in Alzheimer's disease Fundam. Clin. Pharmacol. 22 2008 265 274
12. J. Rodda J. Carter Cholinesterase inhibitors and memantine for symptomatic treatment of dementia BMJ 344 2012 e2986
13. U. Holzgrabe P. Kapkova V. Alptüzün J. Scheiber E. Kugelmann Targeting acetylcholinesterase to treat neurodegeneration Expert Opin. Ther. Targets 11 2007 161 179
14. T. Darreh-Shori H. Soininen Effects of cholinesterase inhibitors on the activities and protein levels of cholinesterases in the cerebrospinal fluid of patients with Alzheimer's disease: a review of recent clinical studies Curr. Alzh. Res. 7 2010 67 73
15. A. Coin E. Perissinotto S. Catanzaro M. Mosele M. De Rui A. Girardi E.M. Inelmen E.D. Toffanello E. Manzato G. Sergi Effects of 21 months of cholinesterase inhibitors on cognitive and functional decline in demented patients Aging Clin. Exper. Res. 24 Suppl. 3 2012 14 16
16. R.M. Lane S.G. Potkin A. Enz Targeting acetylcholinesterase and butyrylcholinesterase in dementia Int. J. Neuropsychopharmacol. 9 2006 101 124
17. A. Alvarez R. Alarcon C. Opazo E.O. Campos F.J. Munoz F.H. Calderon F. Dajas M.K. Gentry B.P. Doctor F.G. De Mello N.C. Interosa Stable complexes involving acetylcholinesterase and amyloid-beta peptide change the biochemical properties of the enzyme and increase the neurotoxicity of Alzheimer's fibrils J. Neurosci. 18 1998 3213 3223
18. M. Bartolini C. Bertucci V. Cavrini V. Andrisano β-Amyloid aggregation induced by human acetylcholinesterase: inhibition studies Biochem. Pharmacol. 65 2003 407 416
19. N.C. Inestrosa A. Alvarez C.A. Pérez R.D. Moreno M. Vicente C. Linker O.I. Casanueva C. Soto J. Garrido Acetylcholinesterase accelerates assembly of amyloid-β-peptides into Alzheimer's fibrils: possible role of the peripheral site of the enzyme Neuron 16 1996 881 891
20. M.C. Dinamarca J.P. Sagal R.A. Quintanilla J.A. Godoy M.S. Arrzola N.C. Inestrosa Amyloid-β-Acetylcholinesterase complexes potentiate neurodegenerative changes induced by the A peptide. Implications for the pathogenesis of Alzheimer's disease Mol. Neurodegener. 5 1 2010 art. no. 4
21. E. Giacobini Cholinesterase inhibitors: new roles and therapeutic alternatives Pharmacol. Res. 50 2004 433 440
22. G. Pepeu M.G. Giovannini Cholinesterase inhibitors and beyond Curr. Alzh. Res. 6 2009 86 96
23. V. Frisardi V. Solfrizzi B.P. Imbimbo C. Capurso A. D'Introno A.M. Colacicco G. Vendemiale D. Seripa A. Pilotto A. Capurso F. Panza Towards disease-modifying treatment of Alzheimer's disease: drugs targeting beta-amyloid Curr. Alzh. Res. 7 2010 40 55
24. R. Morphy Z. Rankovic Designed multiple ligands. An emerging drug discovery paradigm J. Med. Chem. 48 2005 6523 6543
25. K. Iqbal I. Grundke-Iqbal Alzheimer's disease, a multifactorial disorder seeking multitherapies Alzheimers Dement. 6 2010 420 424
26. M.L. Bolognesi R. Matera A. Minarini M. Rosini C. Melchiorre Alzheimer's disease: new approaches to drug discovery Curr. Opin. Chem. Biol. 13 2009 303 308
27. E. Maalej F. Chabchoub M.J. Oset-Gasque M. Esquivias-Pérez M.P. González L. Monjas C. Pérez C. de los Ríos M.I. Rodríguez-Franco I. Iriepa I. Moraleda M. Chioua A. Romero J. Marco-Contelles A. Samadi Synthesis, biological assessment, and molecular modeling of racemic 7-aryl-9,10,11,12-tetrahydro-7 H-benzo[7,8]chromeno[2,3-b]quinolin-8-amines as potential drugs for the treatment of Alzheimer's disease Eur. J. Med. Chem. 54 2012 750 763
28. S. Thiratmatrakul C. Yenjai P. Waiwut O. Vajragupta P. Reubroycharoen M. Tohda C. Boonyarat 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. 75 2014 21 30
29. S.Y. Li X.B. Wang S.S. Xie N. Jiang K.D.G. Wang H.Q. Yao H.B. Sun L.Y. Kong Multifunctional tacrine-flavonoid hybrids with cholinergic, β-amyloid-reducing, and metal chelating properties for the treatment of Alzheimer's disease Eur. J. Med. Chem. 69 2013 632 646
30. S.S. Xie X.B. Wang J.Y. Li L. Wang L.Y. Kong Design, synthesis and evaluation of novel tacrine-coumarin hybrids as multifunctional cholinesterase inhibitors against Alzheimer's disease Eur. J. Med. Chem. 64 2013 540 553
31. Y. He P.-F. Yao S.-B. Chen Z.-H. Huang S.-L. Huang J.-H. Tan D. Li L.-Q. Gu Z.-S. Huang Synthesis and evaluation of 7,8-dehydrorutaecarpine derivatives as potential multifunctional agents for the treatment of Alzheimer's disease Eur. J. Med. Chem. 63 2013 299 312
32. C. Lu Y. Guo J. Yan Z. Luo H.B. Luo M. Yan L. Huang X. Li Design, synthesis, and evaluation of multitarget-directed resveratrol derivatives for the treatment of Alzheimer's disease J. Med. Chem. 56 2013 5843 5859
33. S.-Y. Li X.-B. Wang L.-Y. Kong Design, synthesis and biological evaluation of imine resveratrol derivatives as multi-targeted agents against Alzheimer's disease Eur. J. Med. Chem. 71 2014 36 45
34. L. Fang X. Fang S. Gou A. Lupp I. Lenhardt Y. Sun Z. Huang Y. Chen Y. Zhang C. Fleck Design, synthesis and biological evaluation of D-ring opened galantamine analogs as multifunctional anti-Alzheimer agents Eur. J. Med. Chem. 76 2014 376 386
35. S. Rizzo A. Tarozzi M. Bartolini G. Da Costa A. Bisi S. Gobbi F. Belluti A. Ligresti M. Allarà J.P. Monti V. Andrisano V. Di Marzo P. Hrelia A. Rampa 2-Arylbenzofuran-based molecules as multipotent Alzheimer's disease modifying agents Eur. J. Med. Chem. 58 2012 519 532
36. A. Musial M. Bajda B. Malawska Recent developments in cholinesterases inhibitors for Alzheimer's disease treatment Curr. Med. Chem. 14 2007 2654 2679
37. A. Cavalli M.L. Bolognesi A. Minarini M. Rosini V. Tumiatti M. Recanatini C. Melchiorre Multi-target-directed ligands to combat neurodegenerative diseases J. Med. Chem. 51 2008 347 372
38. M. Bajda M. Ignasik N. Guzior B. Malawska Multi-target-directed ligands in Alzheimer's disease treatment Curr. Med. Chem. 18 2011 4949 4975
39. A. Minarini A. Milelli E. Simoni M. Rosini M.L. Bolognesi C. Marchetti V. Tumiatti Multifunctional tacrine derivatives in Alzheimer's disease Curr. Top. Med. Chem. 13 2013 1771 1786
40. E. Viayna R. Sabate D. Muñoz-Torrero Dual inhibitors of β-amyloid aggregation and acetylcholinesterase as multi-target anti-Alzheimer drug candidates Curr. Top. Med. Chem. 13 2013 1820 1842
41. M. Bajda K. Kuder D. Lażewska K. Kieć-Kononowicz A. Więckowska M. Ignasik N. Guzior J. JoÅ.,czyk B. Malawska Dual-acting diether derivatives of piperidine and homopiperidine with histamine H3 receptor antagonistic and anticholinesterase activity Arch. Pharm. Chem. Life S. C. 345 2012 591 597
42. A. Więckowska M. Bajda N. Guzior B. Malawska Novel alkyl-and arylcarbamate derivatives with N-benzylpiperidine and N-benzylpiperazine moieties as cholinesterases inhibitors Eur. J. Med. Chem. 45 2010 5602 5611
43. M. Ignasik M. Bajda N. Guzior M. Prinz U. Holzgrabe B. Malawska Design, synthesis and evaluation of novel 2-(aminoalkyl)-isoindoline-1,3-dione derivatives as dual-binding site acetylcholinesterase inhibitors Arch. Pharm. Chem. Life S. C. 345 2012 509 516
44. A. Jakubowska K. Kulig N. Guzior B. Malawska Synthesis of novel N-benzyl substituted piperidine amides of 1H-indole-5-carboxylic acid as potential inhibitors of cholinesterases Acta Pol. Pharm. Drug Res. 69 2012 449 455
45. M. Bajda A. Więckowska M. Hebda N. Guzior C. Sotriffer B. Malawska Structure-based search for new inhibitors of cholinesterases Int. J. Mol. Sci. 14 2013 5608 5632
46. G. Kryger I. Silman J.L. Sussman Structure of acetylcholinesterase complexed with E2020 (Aricept®): implications for the design of new anti-Alzheimer drugs Structure 7 1999 297 307
47. H. Sugimoto Y. Iimura Y. Yamanishi K. Yamatsu Synthesis and structure-activity relationships of acetylcholinesterase inhibitors: 1-benzyl-4-[(5,6-dimethoxy-l-oxoindan-2-yl)methyl]piperidine hydrochloride and related compounds J. Med. Chem. 38 1996 4821 4829
48. H.M. Greenblatt C. Guillou D. Guénard A. Argaman S. Botti B. Badet C. Thal I. Silman J.L. Sussman The complex of a bivalent derivative of galanthamine with torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design J. Am. Chem. Soc. 126 2004 15405 15411
49. G.L. Ellman K.D. Courtney V. Andres Jr. R.M. Featherstone A new and rapid colorimetric determination of acetylcholinesterase activity Biochem. Pharmacol. 7 1961 88 95
50. S.L. Chan D.Y. Shirachi H.N. Bhargava E. Gardner A.J. Trevor Purification and properties of multiple forms of brain acetylcholinesterase J. Neurochem. 19 1972 2747 2758
51. B. Cheng H. Gong H. Xiao R.B. Petersen L. Zheng K. Huang Inhibiting toxic aggregation of amyloidogenic proteins: a therapeutic strategy for protein misfolding diseases Biochim. Biophys. Acta 2013 4860 4871
52. H. LeVine Thioflavine t interaction with synthetic Alzheimer's disease beta-amyloid peptides: detection of amyloid aggregation in solution Protein Sci. Publ. Protein Soc. 2 1993 404 410
53. M. Bartolini C. Bertucci M.L. Bolognesi A. Cavalli C. Melchiorre V. Andrisano Insight into the kinetic of amyloid beta(1-42) peptide self-aggregation: elucidation of inhibitors' mechanism of action CHEMBIOCHEM 8 2007 2152 2161
54. E.J. Calabrese L.A. Baldwin Hormesis: U-shaped dose responses and their centrality in toxicology Trends Pharmacol. Sci. 6 2001 285 291
55. E. Arias S. Gallego-Sandin M. Villarroya A.G. Garcia M.G. Lopez Unequal neuroprotection afforded by the acetylcholinesterase inhibitors galantamine, donepezil and rivastigmine in SH-SY5Y neuroblastoma cells: role of nicotinic receptors J. Pharmacol. Exp. Ther. 315 2005 1346 1353
56. T. Lührs C. Ritter M. Adrian D. Riek-Loher B. Bohrmann H. Döbeli D. Schubert R. Riek 3D structure of Alzheimer's amyloid-β(1-42) fibrils PNAS 102 2005 17342 17347
57. M. Landau M.R. Sawaya1 K.F. Faull A. Laganowsky L. Lin Jiang S.A. Sievers J. Liu J.B. Barrio D. Eisenberg PLoS Biol. 9 6 2011 e1001080
58. M. Catto A.A. Berezin D. Lo Re G. Loizou M. Marina Demetriades Design, synthesis and biological evaluation of benzo[e][1,2,4]triazin-7(1H)-one and [1,2,4]-triazino[5,6,1-jk]carbazol-6-one derivatives as dual inhibitors of beta-amyloid aggregation and acetyl/butyryl cholinesterase Eur. J. Med. Chem. 58 2012 84 97
59. D. Karlsson A. Fallarero G. Brunhofer P. Guzik M. Prinz U. Holzgrabe T. Erker P. Vuorela Identification and characterization of diarylimidazoles as hybrid inhibitors of butyrylcholinesterase and amyloid beta fibril formation Eur. J. Pharm. Sci. 45 2012 169 183
60. R.S. Keri C. Quintanova S.M. Marques A.R. Esteves Sandra M. Cardoso M.A. Santos Design, synthesis and neuroprotective evaluation of novel tacrine-benzothiazole hybrids as multi-targeted compounds against Alzheimer's disease Bioorg. Med. Chem. 21 2013 4559 4569
61. E.O. Özer O. Tan K. Ozadali T. Küçükkilinç A. Balkan G. Uçar Synthesis, molecular modeling and evaluation of novel N'-2-(4-benzylpiperidin-/piperazin-1-yl)acylhydrazone derivatives as dual inhibitors for cholinesterases and Aβ aggregation Bioorg. Med. Chem. Lett. 23 2013 440 443
62. H. Tang L.-Z. Zhao H.-T. Zhao S.-L. Huang S.-M. Zhong J.-K. Qin Z.-F. Chen Z.-S. Huang H. Liang Hybrids of oxoisoaporphine-tacrine congeners: novel acetylcholinesterase and acetylcholinesterase-induced β-amyloid aggregation inhibitors Eur. J. Med. Chem. 46 2011 4970 4979
63. C. Galdeano E. Viayn I. Sola X. Formosa P. Camps A. Badia M.V. Clos J. Relat M. Ratia M. Bartolini F. Mancini V. Andrisano M. Salmona C. Minguillón G.C. González-Muñoz M.I. Rodriguez-Franco A. Bidon-Chanal F.J. Luque D. Muñoz-Torrero Huprine-tacrine heterodimers as anti-amyloidogenic compounds of potential interest against Alzheimer's and prion diseases J. Med. Chem. 55 2012 661 669
64. M. Nitsu K. Samejima Syntheses of series of linear pentaamines with three and four methylene chain intervals Chem. Pharm. Bull. 34 1986 1032 1038
65. ONline Demo-Corina. Available online: http://www.molecular-networks.com/online-demos/corina-demo
66. Sybyl 8.0 2007 Tripos St. Louis, MO, USA
67. Protein data Bank. Available online: http://www.pdb.org
68. Gold 4.1 2009 The Cambridge Crystallographic Data Centre Cambridge, UK
69. PyMOL 0.99rc6 2006 DeLano Scientific LLC Palo Alto, CA, USA
70. A. Altomare G. Cascarano G. Giacovazzo A. Guagliardi M.C. Burla G. Polidori M. Camalli J. Appl. Cryst. 27 1994 435
71. G.M. Sheldrick A short history of SHELX Acta Crystallogr. 2008 112 122 Sect. A64