Multifunctional cholinesterase and amyloid beta fibrillization modulators. Synthesis and biological investigation

ACS Medicinal Chemistry Letters

Volumn 4, Issue 12, 2013, Pages 1178-1182

  Butini, Stefania ^a   Brindisi, Margherita ^a   Brogi, Simone ^a   Maramai, Samuele ^a   Guarino, Egeria ^a   Panico, Alessandro ^a   Saxena, Ashima ^b   Chauhan, Ved ^c   Colombo, Raffaella ^d   Verga, Laura ^e   De Lorenzi, Ersilia ^d   Bartolini, Manuela ^f   Andrisano, Vincenza ^f   Novellino, Ettore ^a,g   Campiani, Giuseppe ^a   Gemma, Sandra ^a  

^a UNIVERSITY OF SIENA   (Italy)

^b WALTER REED ARMY INSTITUTE OF RESEARCH   (United States)

^c NEW YORK STATE INSTITUTE FOR BASIC RESEARCH IN DEVELOPMENTAL DISABILITIES   (United States)

^d UNIVERSITY OF PAVIA   (Italy)

^e FONDAZIONE IRCCS POLICLINICO SAN MATTEO   (Italy)

^f UNIVERSITY OF BOLOGNA   (Italy)

^g UNIVERSITY OF NAPLES FEDERICO II   (Italy)

Author keywords

Alzheimer's disease; amyloid beta oligomers; amyloid beta peptides; bivalent ligands; Cholinesterase inhibitors; multifunctional tools

Indexed keywords

ACETYLCHOLINESTERASE; AMYLOID BETA PROTEIN; CHOLINESTERASE;

ARTICLE; BINDING SITE; CAPILLARY ELECTROPHORESIS; CATALYSIS; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; DEPLETION; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; MOLECULAR DOCKING; MOLECULAR MODEL; MOLECULAR WEIGHT; OLIGOMERIZATION; PRECIPITATION; PRIORITY JOURNAL; PROTEIN FUNCTION; SYNTHESIS; TRANSMISSION ELECTRON MICROSCOPY;

EID: 84890458088     PISSN: None     EISSN: 19485875     Source Type: Journal    
DOI: 10.1021/ml4002908     Document Type: Article

References (24)

1. Lauren, J.; Gimbel, D. A.; Nygaard, H. B.; Gilbert, J. W.; Strittmatter, S. M. Cellular prion protein mediates impairment of synaptic plasticity by amyloid-beta oligomers Nature 2009, 457, 1128-1132
2. Cavalli, A.; Bolognesi, M. L.; Capsoni, S.; Andrisano, V.; Bartolini, M.; Margotti, E.; Cattaneo, A.; Recanatini, M.; Melchiorre, C. A small molecule targeting the multifactorial nature of Alzheimer's disease Angew. Chem., Int. Ed. 2007, 46, 3689-3692
3. Sadowski, M.; Wisniewski, T. Disease modifying approaches for Alzheimer's pathology Curr. Pharm. Des. 2007, 13, 1943-1954
4. McShane, R.; Areosa Sastre, A.; Minakaran, N. Memantine for dementia Cochrane Database Syst. Rev. 2006, CD003154
5. Cummings, J. L. Treatment of Alzheimer's disease: Current and future therapeutic approaches Rev. Neurol. Dis. 2004, 1, 60-69
6. Greenblatt, H. M.; Dvir, H.; Silman, I.; Sussman, J. L. Acetylcholinesterase: A multifaceted target for structure-based drug design of anticholinesterase agents for the treatment of Alzheimer's disease J. Mol. Neurosci. 2003, 20, 369-383
7. Alvarez, A.; Opazo, C.; Alarcon, R.; Garrido, J.; Inestrosa, N. C. Acetylcholinesterase promotes the aggregation of amyloid-beta-peptide fragments by forming a complex with the growing fibrils J. Mol. Biol. 1997, 272, 348-361
8. 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 beta-peptide fibril formation Biochemistry 2001, 40, 10447-10457
9. Soreq, H.; Seidman, S. Acetylcholinesterase: new roles for an old actor Nat. Rev. Neurosci. 2001, 2, 294-302
10. Bartolini, M.; Bertucci, C.; Cavrini, V.; Andrisano, V. beta-Amyloid aggregation induced by human acetylcholinesterase: Inhibition studies Biochem. Pharmacol. 2003, 65, 407-416
11. Reyes, A. E.; Chacon, M. A.; Dinamarca, M. C.; Cerpa, W.; Morgan, C.; Inestrosa, N. C. Acetylcholinesterase-Abeta complexes are more toxic than Abeta fibrils in rat hippocampus: Effect on rat beta-amyloid aggregation, laminin expression, reactive astrocytosis, and neuronal cell loss Am. J. Pathol. 2004, 164, 2163-2174
12. Darvesh, S.; Cash, M. K.; Reid, G. A.; Martin, E.; Mitnitski, A.; Geula, C. Butyrylcholinesterase is associated with beta-amyloid plaques in the transgenic APPSWE/PSEN1dE9 mouse model of Alzheimer disease J. Neuropathol. Exp. Neurol. 2012, 71, 2-14
13. Benilova, I.; Karran, E.; De Strooper, B. The toxic Abeta oligomer and Alzheimer's disease: An emperor in need of clothes Nat. Neurosci. 2012, 15, 349-357
14. Hamley, I. W. The amyloid beta peptide: A chemist's perspective. Role in Alzheimer's and fibrillization Chem. Rev. 2012, 112, 5147-5192
15. Butini, S.; Campiani, G.; Borriello, M.; Gemma, S.; Panico, A.; Persico, M.; Catalanotti, B.; Ros, S.; Brindisi, M.; Agnusdei, M.; Fiorini, I.; Nacci, V.; Novellino, E.; Belinskaya, T.; Saxena, A.; Fattorusso, C. Exploiting protein fluctuations at the active-site gorge of human cholinesterases: further optimization of the design strategy to develop extremely potent inhibitors J. Med. Chem. 2008, 51, 3154-3170
16. Colletier, J. P.; Sanson, B.; Nachon, F.; Gabellieri, E.; Fattorusso, C.; Campiani, G.; Weik, M. Conformational flexibility in the peripheral site of Torpedo californica acetylcholinesterase revealed by the complex structure with a bifunctional inhibitor J. Am. Chem. Soc. 2006, 128, 4526-4527
17. Pang, Y. P.; Quiram, P.; Jelacic, T.; Hong, F.; Brimijoin, S. Highly potent, selective, and low cost bis-tetrahydroaminacrine inhibitors of acetylcholinesterase. Steps toward novel drugs for treating Alzheimer's disease J. Biol. Chem. 1996, 271, 23646-23649
18. Camps, P.; Formosa, X.; Galdeano, C.; Gomez, T.; Munoz-Torrero, D.; Ramirez, L.; Viayna, E.; Gomez, E.; Isambert, N.; Lavilla, R.; Badia, A.; Clos, M. V.; Bartolini, M.; Mancini, F.; Andrisano, V.; Bidon-Chanal, A.; Huertas, O.; Dafni, T.; Luque, F. J. Tacrine-based dual binding site acetylcholinesterase inhibitors as potential disease-modifying anti-Alzheimer drug candidates Chem. Biol. Interact. 2010, 187, 411-415
19. Minarini, A.; Milelli, A.; Tumiatti, V.; Rosini, M.; Simoni, E.; Bolognesi, M. L.; Andrisano, V.; Bartolini, M.; Motori, E.; Angeloni, C.; Hrelia, S. Cystamine-tacrine dimer: A new multi-target-directed ligand as potential therapeutic agent for Alzheimer's disease treatment Neuropharmacology 2012, 62, 997-1003
20. Bolognesi, M. L.; Cavalli, A.; Valgimigli, L.; Bartolini, M.; Rosini, M.; Andrisano, V.; Recanatini, M.; Melchiorre, C. Multi-target-directed drug design strategy: from a dual binding site acetylcholinesterase inhibitor to a trifunctional compound against Alzheimer's disease J. Med. Chem. 2007, 50, 6446-6449
21. Sanson, B. Dynamique structurale de l'acétylcholinestérase étudiée par cristallographie aux rayons X et par une méthode spectroscopique complémentaire. Ph.D. Thesis, Université Joseph Fourie, Grenoble I, 2009; see http://www.ibs.fr/ science/production-scientifique/theses-soutenues-a-l-ibs/?lang=fr. The refined X-ray structure will be reported elsewhere.
22. Schrödinger Suite 2011 Induced Fit Docking; Glide version 5.7; Prime version 3.0; Schrödinger, LLC: New York, 2011.
23. Sabella, S.; Quaglia, M.; Lanni, C.; Racchi, M.; Govoni, S.; Caccialanza, G.; Calligaro, A.; Bellotti, V.; De Lorenzi, E. Capillary electrophoresis studies on the aggregation process of beta-amyloid 1-42 and 1-40 peptides Electrophoresis 2004, 25, 3186-3194
24. Colombo, R.; Carotti, A.; Catto, M.; Racchi, M.; Lanni, C.; Verga, L.; Caccialanza, G.; De Lorenzi, E. CE can identify small molecules that selectively target soluble oligomers of amyloid beta protein and display antifibrillogenic activity Electrophoresis 2009, 30, 1418-1429