Multigram synthesis and in Vivo efficacy studies of a novel multitarget anti-alzheimer's compound

Molecules

Volumn 20, Issue 3, 2015, Pages 4492-4515

  Sola, Irene ^a   Viayna, Elisabet ^a   Gómez, Tània ^a   Galdeano, Carles ^a   Cassina, Matteo ^a   Camps, Pelayo ^a   Romeo, Margherita ^b   Diomede, Luisa ^b   Salmona, Mario ^b   Franco, Pilar ^c   Schaeffer, Mireille ^c   Colantuono, Diego ^c   Robin, David ^c   Brunner, Daniela ^d   Taub, Nicole ^d   Hutter Paier, Birgit ^d   Muñoz Torrero, Diego ^a  

^a UNIVERSITY OF BARCELONA   (Spain)

^b MARIO NEGRI INSTITUTE FOR PHARMACOLOGICAL RESEARCH   (Italy)

^c Chiral Technologies Europe   (France)

^d Neuropharmacology Department of QPS Austria Gmbh   (Austria)

Author keywords

Animal models of alzheimer's disease; Disease modifying anti alzheimer drugs; Multigram preparative chromatographic resolution; Multitarget drugs; Neuroprotection

Indexed keywords

AMINOQUINOLINE DERIVATIVE; AMYLOID PRECURSOR PROTEIN; APP PROTEIN, HUMAN; AVCRI104P4; DONEPEZIL; FUSED HETEROCYCLIC RINGS; HUPRINE Y; INDAN DERIVATIVE; PIPERIDINE DERIVATIVE;

ALZHEIMER DISEASE; ANIMAL; BRAIN; CAENORHABDITIS ELEGANS; CHEMICAL STRUCTURE; CHEMISTRY; DISEASE MODEL; GENETICS; HEPG2 CELL LINE; HUMAN; METABOLISM; MOUSE; PATHOLOGY; TRANSGENIC ANIMAL;

ALZHEIMER DISEASE; AMINOQUINOLINES; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; ANIMALS, GENETICALLY MODIFIED; BRAIN; CAENORHABDITIS ELEGANS; DISEASE MODELS, ANIMAL; HEP G2 CELLS; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; HUMANS; INDANS; MICE; MOLECULAR STRUCTURE; PIPERIDINES;

EID: 84928814864     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules20034492     Document Type: Article

References (44)

1. Prince, M.; Albanese, E.; Guerchet, M.; Prina, M. World Alzheimer Report 2014: Dementia and Risk Reduction; Alzheimer's Disease International: London, UK, 2014. Available online: http://www.alz.co.uk (accessed on 20 February 2015).
2. Hardy, J.; Selkoe, D.J. The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science 2002, 297, 353-356.
3. Citron, M. Alzheimer's disease: Strategies for disease modification. Nat. Rev. Drug Discov. 2010, 9, 387-398.
4. Pimplikar, S.W. Reassessing the amyloid cascade hypothesis of Alzheimer's disease. Int. J. Biochem. Cell Biol. 2009, 41, 1261-1268.
5. Cavalli, A.; Bolognesi, M.L.; Minarini, A.; Rosini, M.; Tumiatti, V.; Recanatini, M.; Melchiorre, C. Multi-target-directed ligands to combat neurodegenerative diseases. J. Med. Chem. 2008, 51, 347-372.
6. Guzior, N.; Więckowska, 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.
7. Geldenhuys, W.J.; van der Schyf, C.J. Rationally designed multi-targeted agents against neurodegenerative diseases. Curr. Med. Chem. 2013, 20, 1662-1672.
8. Chen, X.; Decker, M. Multi-target compounds acting in the central nervous system designed from natural products. Curr. Med. Chem. 2013, 20, 1673-1685.
9. Russo, P.; Frustaci, A.; Del Bufalo, A.; Fini, M.; Cesario, A. Multitarget drugs of plants origin acting on Alzheimer's disease. Curr. Med. Chem. 2013, 20, 1686-1693.
10. Capurro, V.; Busquet, P.; Lopes, J.P.; Bertorelli, R.; Tarozzo, G.; Bolognesi, M.L.; Piomelli, D.; Reggiani, A.; Cavalli, A. Pharmacological characterization of memoquin, a multitarget compound for the treatment of Alzheimer's disease. PLoS One 2013, 8, e56870.
11. Antequera, D.; Bolos, M.; Spuch, C.; Pascual, C.; Ferrer, I.; Fernandez-Bachiller, M.I.; Rodríguez-Franco, M.I.; Carro, E. Effects of a tacrine-8-hydroxyquinoline hybrid (IQM-622) on Aβ accumulation and cell death: Involvement in hippocampal neuronal loss in Alzheimer's disease. Neurobiol. Dis. 2012, 46, 682-691.
12. Viayna, E.; Gómez, T.; Galdeano, C.; Ramírez, L.; Ratia, M.; Badia, A.; Clos, M.V.; Verdaguer, E.; Junyent, F.; Camins, A.; et al. Novel huprine derivatives with inhibitory activity toward β-amyloid aggregation and formation as disease-modifying anti-Alzheimer drug candidates. ChemMedChem 2010, 5, 1855-1870.
13. 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.
14. 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.
15. 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.
16. Castro, A.; Martinez, A. Targeting beta-amyloid pathogenesis through acetylcholinesterase inhibitors. Curr. Pharm. Des. 2006, 12, 4377-4387.
17. Muñoz-Torrero, D. Acetylcholinesterase inhibitors as disease-modifying therapies for Alzheimer's disease. Curr. Med. Chem. 2008, 15, 2433-2455.
18. 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.
19. Morphy, R.; Rankovic, Z. Designed multiple ligands. An emerging drug discovery paradigm. J. Med. Chem. 2005, 48, 6523-6543.
20. Zhang, T.; Nguyen, D.; Franco, P. Enantiomer resolution screening strategy using multiple immobilised polysaccharide-based chiral stationary phases. J. Chromatogr. A 2008, 1191, 214-222.
21. Franco, P.; Zhang, T. Common approaches for efficient method development with immobilised polysaccharide-derived chiral stationary phases. J. Chromatogr. B 2008, 875, 48-56.
22. Zhang, T.; Schaeffer, M.; Franco, P. Optimization of the chiral separation of a Ca-sensitizing drug on an immobilized polysaccharide-based chiral stationary phase. Case study with a preparative perspective. J. Chromatogr. A 2005, 1083, 96-101.
23. Bertz, S.H. Tetramethyl 3,7-dihydroxybicyclo[3.3.1]nona-2,6-diene-2,4,6,8-tetracarboxylate: A useful companion to Meerwein's ester. Topological analysis of bicyclo[3.3.1]nonane synthesis. J. Org. Chem. 1985, 50, 3585-3592.
24. Camps, P.; El Achab, R.; Font-Bardia, M.; Görbig, D.; Morral, J.; Muñoz-Torrero, D.; Solans, X.; Simon, M. Easy synthesis of 7-alkylbicyclo[3.3.1]non-6-en-3-ones by silica gel-promoted fragmentation of 3-alkyl-2-oxaadamant-1-yl mesylates. Tetrahedron 1996, 52, 5867-5880.
25. Ronco, C.; Jean, L.; Renard, P.-Y. Improved synthetic pathway for the derivatization of huprine scaffold. Tetrahedron 2010, 66, 7399-7404.
26. Camps, P.; Contreras, J.; Font-Bardia, M.; Morral, J.; Muñoz-Torrero, D.; Solans, X. Enantioselective synthesis of tacrine-huperzine A hybrids. Preparative chiral MPLC separation of their racemic mixtures and absolute configuration assignments by X-ray diffraction analysis. Tetrahedron Asymmetry 1998, 9, 835-849.
27. Camps, P.; Formosa, X.; Galdeano, C.; Gómez, T.; Muñoz-Torrero, D.; Scarpellini, M.; Viayna, E.; Badia, A.; Clos, M.V.; Camins, A.; et al. Novel donepezil-based inhibitors of acetyl- and butyrylcholinesterase and acetylcholinesterase-induced β-amyloid aggregation. J. Med. Chem. 2008, 51, 3588-3598.
28. Volovik, Y.; Carvalhal Marques, F.; Cohen, E. The nematode Caenorhabditis elegans: A versatile model for the study of proteotoxicity and aging. Methods 2014, 68, 458-464.
29. Hassan, W.M.; Dostal, V.; Huemann, B.N.; Yerg, J.E.; Link, C.D. Identifying Aβ-specific pathogenic mechanisms using a nematode model of Alzheimer's disease. Neurobiol. Aging 2015, 36, 857-866, doi:10.1016/j.neurobiolaging.2014.10.016.
30. Li, J.; Le, W. Modeling neurodegenerative diseases in Caenorhabditis elegans. Exp. Neurol. 2013, 250, 94-103.
31. Sashidhara, K.V.; Modukuri, R.K.; Jadiya, P.; Prasad Dodda, R.; Kumar, M.; Sridhar, B.; Kumar, V.; Haque, R.; Imran Siddiqi, M.; Nazir, A. Benzofuran-chalcone hybrids as potential multifunctional agents against Alzheimer's disease: Synthesis and in vivo studies with transgenic Caenorhabditis elegans. ChemMedChem 2014, 9, 2671-2684.
32. Cao, Y.; Wang, L.; Lin, Z.; Liang, F.; Pei, Z.; Xu, J.; Gu, Q. Dehydroabietylamine derivatives as multifunctional agents for the treatment of Alzheimer's disease. Med. Chem. Commun. 2014, 5, 1736-1743.
33. Cao, Y.Y.; Wang, L.; Ge, H.; Lu, X.L.; Pei, Z.; Gu, Q.; Xu, J. Salvianolic acid A, a polyphenolic derivative from Salvia miltiorrhiza bunge, as a multifunctional agent for the treatment of Alzheimer's disease. Mol. Divers. 2013, 17, 515-524.
34. Link, C.D. Invertebrate models of Alzheimer's disease. Genes Brain Behav. 2005, 4, 147-156.
35. Diomede, L.; Rigacci, S.; Romeo, M.; Stefani, M.; Salmona, M. Oleuropein aglycone protects transgenic C. elegans strains expressing Aβ42 by reducing plaque load and motor deficit. PLoS One 2013, 8, e58893.
36. Diomede, L.; Cassata, G.; Fiordaliso, F.; Salio, M.; Ami, D.; Natalello, A.; Doglia, S.M.; De Luigi, A.; Salmona, M. Tetracycline and its analogues protect Caenorhabditis elegans from β amyloid-induced toxicity by targeting oligomers. Neurobiol. Dis. 2010, 40, 424-431.
37. Beeg, M.; Diomede, L.; Stravalaci, M.; Salmona, M.; Gobbi, M. Novel approaches for studying amyloidogenic peptides/proteins. Curr. Opin. Pharmacol. 2013, 13, 797-801.
38. Stoilova, T.; Colombo, L.; Forloni, G.; Tagliavini, F.; Salmona, M. A new face for old antibiotics: Tetracyclines in treatment of amyloidoses. J. Med. Chem. 2013, 56, 5987-6006.
39. Zhang, L.; Yu, H.; Li, W.M.; Cheung, M.C.; Pang, Y.P.; Gu, Z.M.; Chan, K.; Wang, Y.T.; Zuo, Z.; Han, Y.F. Preclinical characterization of intestinal absorption and metabolism of promising anti-Alzheimer's dimer bis(7)-tacrine. Int. J. Pharm. 2008, 357, 85-94.
40. Pan, S.Y.; Yu, Z.L.; Dong, H.; Lee, N.T.K.; Wang, H.; Fong, W.F.; Han, Y.F.; Ko, K.M. Evaluation of acute bis(7)-tacrine treatment on behavioral functions in 17-day-old and 30-day-old mice, with attention to drug toxicity. Pharmacol. Biochem. Behav. 2007, 86, 778-783.
41. Qian, S.; He, L.; Mak, M.; Han, Y.; Ho, C.-Y.; Zuo, Z. Synthesis, biological activity, and biopharmaceutical characterization of tacrine dimers as acetylcholinesterase inhibitors. Int. J. Pharm. 2014, 477, 442-453.
42. Wu, Y.; Wu, Z.; Butko, P.; Christen, Y.; Lambert, M.P.; Klein, W.L.; Link, C.D.; Luo, Y. Amyloid-β-induced pathological behaviors are suppressed by Ginkgo biloba extract EGb 761 and ginkgolides in transgenic Caenorhabditis elegans. J. Neurosci. 2006, 26, 13102-13113.
43. Styren, S.D.; Hamilton, R.L.; Styren, G.C.; Klunk, W.E. X-34, a fluorescent derivative of Congo red: A novel histochemical stain for Alzheimer's disease pathology. J. Histochem. Cytochem. 2000, 48, 1223-1232.
44. Havas, D.; Hutter-Paier, B.; Ubhi, K.; Rockenstein, E.; Crailsheim, K.; Masliah, E.; Windisch, M. A longitudinal study of behavioral deficits in an AßPP transgenic mouse model of Alzheimer's disease. J. Alzheimers Dis. 2011, 25, 231-243.