7-methoxytacrine-adamantylamine heterodimers as cholinesterase inhibitors in Alzheimer's disease treatment - Synthesis, biological evaluation and molecular modeling studies

Molecules

Volumn 18, Issue 2, 2013, Pages 2397-2418

  Spilovska, Katarina ^a   Korabecny, Jan ^a,b   Kral, Jan ^c   Horova, Anna ^a   Musilek, Kamil ^a,b,d   Soukup, Ondrej ^b   Drtinova, Lucie ^a   Gazova, Zuzana ^e   Siposova, Katarina ^e,f   Kuca, Kamil ^b,g  

^a UNIVERSITY OF DEFENCE   (Czech Republic)

^b UNIVERSITY HOSPITAL HRADEC KRALOVE   (Czech Republic)

^c Charles University in Prague Faculty of Pharmacy   (Czech Republic)

^d UNIVERSITY OF HRADEC KRALOVE   (Czech Republic)

^e INSTITUTE OF EXPERIMENTAL PHYSICS   (Slovakia)

^f P J AFÁRIK UNIVERSITY   (Slovakia)

^g UNIVERSITY OF DEFENCE   (Czech Republic)

Author keywords

7 MEOTA; Acetylcholinesterase; Alzheimer's disease; Amantadine; Butyrylcholinesterase; Inhibitor

Indexed keywords

7 METHOXYTACRINE; ACETYLCHOLINESTERASE; AMANTADINE; CHOLINESTERASE INHIBITOR; DRUG DERIVATIVE; TACRINE; THIOUREA;

ALZHEIMER DISEASE; ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; DIMERIZATION; ENZYME ASSAY; HUMAN; IC 50; METABOLISM; MOLECULAR DOCKING; STANDARD; SYNTHESIS;

ACETYLCHOLINESTERASE; ALZHEIMER DISEASE; AMANTADINE; CHOLINESTERASE INHIBITORS; DIMERIZATION; ENZYME ASSAYS; HUMANS; INHIBITORY CONCENTRATION 50; MODELS, MOLECULAR; MOLECULAR DOCKING SIMULATION; REFERENCE STANDARDS; TACRINE; THIOUREA;

MLCS; MLOWN;

EID: 84874613897     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules18022397     Document Type: Article

References (65)

1. Lipton, S.A. The molecular basis of memantine action in Alzheimer's disease and other neurologic disorders: Low-affinity, Uncompetitive antagonism. Curr. Alzheimer Res. 2005, 2, 155-165. (Pubitemid 40862876)
2. Dominguez, E.; Chin, T.Y.; Chen, C.P.; Wu, T.Y. Management of moderate to severe Alzheimer's disease: Focus on memantine. Taiwan J. Obstet. Gynecol. 2011, 50, 415-423.
3. Benzi, G.; Moretti, A. Is there a rationale for use of acetylcholinesterase inhibitors in the therapy of Alzheimer's disease? Eur. J. Pharmacol. 1998, 346, 1-13. (Pubitemid 28197082)
4. Walsh, D.M.; Selkoe, D.J. Deciphering the molecular basis of memory failure in Alzheimer's disease. Neuron 2004, 44, 181-193. (Pubitemid 39348839)
5. Belluti, F.; Bartolini, M.; Bottegoni, G.; Bisi, A.; Cavalli, A.; Andrisano, V.; Rampa, A. Benzophenone-based derivatives: A novel series of potent and selective dual inhibitors of acetylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation. Eur. J. Med. Chem. 2011, 46, 1682-1693.
6. Scarpini, E.; Scheltens, P.; Feldman, H. Treatment of Alzheimer's disease: Current status and new perspectives. Lancet Neurol. 2003, 2, 39-47.
7. Shan, W.J.; Huang, L.; Zhou, Q.; Meng, F.C.; Li, X.S. Synthesis, biological evaluation of 9-N-substituted berberine derivatives as multifunctional agents of antioxidant, inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation. Eur. J. Med. Chem. 2011, 46, 5885-5893.
8. Guo, T.; Hobbs, D.W. Development of BACE1 inhibitors for Alzheimer's disease. 2006, 13, 1811-1829.
9. Zhu, Y.; Xiao, L.; Xiong, B.; Fu, Y.; Yu, H.; Wang, W.; Wang, X.; Hu, D.; Peng, H.; Li, J.; et al. Design, Synthesis and biological evaluation of novel dual inhibitors of acetylcholinesterase and beta-secretase. Bioorg. Med. Chem. 2009, 17, 1600-1613.
10. Bartus, R.T.; Dean 3rd, R.L.; Beer, B.; Lippa, A.S. Thee cholinergic hypothesis of geriatric memory dysfunction. Science 1982, 217, 408-414.
11. Terry, Jr, A.V.; Buccafusco, J.J. The cholinergic hypothesis age and Alzheimer's disease- related cognitive deficits: Recent challenges and their implications for novel drug development. J. Pharmacol. Exp. Ther. 2003, 306, 821-827. (Pubitemid 37025286)
12. Whitehouse, P.J. Cholinergic therapy in dementia. Acta Neurol. Scand. Suppl. 1993, 149, 42-45. (Pubitemid 24027491)
13. Kelly, C.A.; Harvey, R.J.; Cayton, H. Drug treatments for Alzheimer's disease. BMJ 1997, 314, 693-694. (Pubitemid 27113069)
14. Scott, L.J.; Goa, K.L. Galantamine: A review of its use in Alzheimer's disease. Drug 2000, 60, 1095-1122.
15. Bielavsky, J. Analogues of 9-amino-1,2,3,4-tetrahydroacridine. Collect. Czech. Chem. Commun. 1977, 42, 2802-2808.
16. Yan, A.; Wang, K. Quantitative structure and bioactivity relationship study on human acetylcholinesterase inhibitors. Bioorg. Med. Chem. Lett. 2012, 22, 3336-3342.
17. Birks, J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst. Rev. 2006, CD005593.
18. McShane, R.; Areosa Sastre, A.; Minakaran, N. Memantine for dementia. Cochrane Database Syst. Rev. 2006, CD003154.
19. Weiner, M.W.; Sadowsky, C.; Saxton, J.; Hofbauer, R.K.; Graham, S.M.; Yu, S.Y.; Li, S.; Hsu, H.A.; Suhy, J.; Fridman, M.; et al. Magnetic resonance imaging and neuropsychological results from a trial of memantine in Alzheimer's disease. Alzheimers Dement. 2011, 7, 425-435.
20. Munoz-Torrero, D. Acetylcholinesterase inhibitors as disease-modifying therapies for Alzheimer's disease. Curr. Med. Chem. 2008, 15, 2433-2455.
21. Chen, H.S.; Pellegrini, J.W.; Aggarwall, S.K.; Lei, S.Z.; Warach, S.; Jensen, F.E.; Lipton, S.A. Open-channel block of N-metyhl-D-aspartate (NMDA) responses by memantine: Therapeutic advantage against NMDA receptor-mediated neurotoxicity. J. Neurosci. 1992, 12, 4427-4436.
22. Parson, C.G.; Danysz, W.; Quack, G. Memantine is a clinically well tolerated N-methyl-Daspartate (NMDA) receptor antagonist - A review of preclinical data. Neuropharmacology 1999, 38, 735-767. (Pubitemid 29187336)
23. Wu, H.M. Tzeng, N.S.; Qian, L.; Wei, S.J.; Hu, X.; Chen, H.S.; Rawls, S.M.; Flood, P.; Hong, J.S.; Lu, R.B. Novel neuroprotective mechanisms of memantine: increase in neurotropic factor release from astroglia and anti-inflammation by preventing microglial activation. Neuropsychopharmacology 2009, 34, 2344-2357.
24. Kim, J.H.; Lee, H.W.; Hwang, J.; Kim, J.; Lee, M.J.; Han, H.S.; Lee, W.H.; Suk, K. Microglialinhibiting activity of Parkinson's disease drug amantadine. Neurobiol. Aging 2012, 33, 2145-2159.
25. Kornhuber, J.; Bormann, J.; Hübers, M.; Rusche, K.; Riederer, P. Effects of the 1-aminoadamantanes at the MK-801-binding site of the NMDA-receptor-gated ion channel: A human postmortem brain study. Eur. J. Pharmacol. 1991, 206, 297-300.
26. Inzelberg, R.; Bonuccelli, U.; Schechtman, E.; Miniowich, A.; Strugatsky, R.; Ceravolo, R.; Logi, C.; Rossi, C.; Klein, C.; Rabey, J.M. Association between amantadine and the onset of dementia in Parkinson's disease. Mor. Disord. 2006, 21, 1375-1379. (Pubitemid 44613288)
27. Robinson, D.M.; Keating, G.M. Memantine: A review of its use in Alzheimer's disease. Drugs 2006, 66, 1515-1534. (Pubitemid 44250755)
28. Dejmek, L. 7-MEOTA. Drug. Future 1990, 15, 126.
29. Watkins, P.B.; Zimmerman, H.J.; Knapp, M.J.; Gracon, S.I.; Lewis, K.W. Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease. JAMA 1994, 271, 992-998. (Pubitemid 24099919)
30. Patocka, J.; Jun, D.; Kuca, K. Possible role of hydroxylated metabolites of tacrine in drug toxicity and therapy of Alzheimer's disease. Curr. Drug. MeTable 2008, 9, 332-335. (Pubitemid 351836422)
31. Korabecny, J.; Musilek, K.; Zemek, F.; Horova, A.; Holas, O.; Nepovimova, E.; Opletalova, V.; Hroudova, J.; Fisar, Z.; Jung, Y.S.; et al. Synthesis and in vitro evaluation of 7-methoxy-N-(pent- 4-enyl)-1,2,3,4-tetrahydroacridin-9- amine - New tacrine derivative with cholinergic properties. Bioorg. Med. Chem. Lett. 2011, 21, 6563-6566.
32. Korabecny, J.; Musilek, K.; Holas, O.; Nepovimova, E.; Jun, D.; Zemek, F.; Opletalova, V.; Patocka, J.; Dohnal, V.; Nachon, F.; et al. Synthesis and in vitro evaluation of N-(Bromobut-3-en- 2-yl)-7-methoxy-1,2,3,4- tetrahydroacridin-9-amine as a cholinesterase inhibitor with regard to Alzheimer's disease treatment. Molecules 2010, 15, 8804-8812.
33. Korabecny, J.; Musilek, K.; Holas, O.; Binder, J.; Zemek, F.; Marek, J.; Pohanka, M.; Opletalova, V.; Dohnal, V.; Kuca, K. Synthesis and in vitro evaluation of N-alkyl-7- methoxytacrine hydrochlorides as potential cholinesterase inhibitors in Alzheimer disease. Bioorg. Med. Chem. Lett. 2010, 20, 6093-6095.
34. Korabecny, J.; Holas, O.; Musilek, K.; Pohanka, M.; Opletalova, V.; Dohnal, V.; Kuca, K. Synthesis and in vitro evaluation of new tacrine derivatives - Bis-alkylene linked 7-MEOTA. Lett. Org. Chem. 2010, 7, 327-331.
35. Youdim, M.B.; Buccafusco, J.J. Multi-functional drugs for various CNS targets in the treatment of neurodegenerative disorders. Trends Pharmacol. Sci. 2005, 26, 27-35. (Pubitemid 40052707)
36. 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. (Pubitemid 351252260)
37. Kozurkova, M.; Hamulakova, S.; Gazova, Z.; Paulikova, H.; Kristian, P. Neuroactive Multifunctional Tacrine Congeners with Cholinesterase, Anti-Amyloid Aggregation and Neuroprotective Properties. Pharmaceuticals 2011, 4, 382-418.
38. Melchiorre, C. Andrisano, V.; Bolognesi, M.L.; Budriesi, R.; Cavalli, A.; Cavrini, A.; Rosini, M.; Tumiatti, V.; Recanatini, M. Acetylcholinesterase noncovalent inhibitors based on a polyamine backbone for potential use against Alzheimer's disease. J. Med. Chem. 1998, 41, 4186-4189. (Pubitemid 28498739)
39. Sterling, J.; Herzig, Y.; Goren, T.; Finkelstein, N.; Lerner, D.; Goldenberg, W.; Miskolezi, I.; Molnar, S.; Rantal, F.; Tamas, T.; et al. Novel dual inhibitors of AchE and MAO derived from hydroxy aminoindan and phenethylamine as potential treatment for Alzheimer's disease. J. Med. Chem. 2002, 45, 5260-5279. (Pubitemid 35429165)
40. Zheng, H.; Amit, T.; Bar-Am, O.; Fridkin, M.; Youdim, M.B.; Mandel, S.A. From anti-Parkinson's drug rasagiline to novel multitarget iron chelators with acetylcholinesterase and monoamine oxidase inhibitory and neuroprotective properties for Alzheimer's disease. J. Alzheimers Dis. 2012, 30, 1-16.
41. Weinreb, O.; Amit, T.; Bar-Am, O.; Youdim, M.B. Ladostigil: a novel multimodal neuroprotective drug with cholinesterase and brain- selective monoamine oxidase inhibitory activities for Alzheimer's disease treatment. Curr. Drug Targets 2012, 13, 483-494.
42. Kogen, H.; Toda, N.; Tago, K.; Marumoto, S.; Takami, K.; Ori, M.; Yamada, N.; Koyama, K.; Naruto, S.; Abe, K.; et al. Design and synthesis of dual inhibitors of acetylcholinesterase and serotonin transporter targeting potential agents for Alzheimer's disease. Org. Lett. 2002, 4, 3359-3362.
43. Toda, N.; Kaneko, T.; Kogen, H. Development of an efficient therapeutic agent for Alzheimer's disease: Design and synthesis of dual inhibitors of acetylcholinesterase and serotonin transporter. Chem. Pharm. Bull. (Tokyo) 2011, 58, 273-287.
44. 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. Engl. 2007, 46, 3689-3692. (Pubitemid 46981250)
45. Hamulakova, S.; Janovec, L.; Hrabinova, M.; Kristian, P.; Kuca, K.; Banasova, M. Synthesis, Design and biological evaluation of novel highly potent tacrine congeners for the treatment of Alzheimer's disease. Eur. J. Med. Chem. 2012, 55, 23-31.
46. Di Santo, R.; Costi, R.; Cuzzucoli Crucitti, G.; Pescatori, L.; Rosi, F.; Scipione, L.; Celona, D.; Vertechy, M.; Ghirardi, O.; Piovesan, P.; et al. Design, Synthesis, and Structure - activity relationship of N-arylnaphtylmine derivatives as amyloid aggregation inhibitors. J. Med. Chem. 2012, 55, 8538-8548.
47. Chen, Y.; Sun, J.; Fang, L.; Liu, M.; Peng, S.; Liao, H.; Lehmann, J.; Zhang, Y. Tacrine-ferulic acid-nitric oxide (NO) donor trihybrids os potent, multifunctional acetyl- and butyrylcholinesterase inhibitors. J. Med. Chem. 2012, 55, 4309-4321.
48. Fernandez-Bachiller, M.I.; Perez, C.; Monjas, L.; Rademann, J.; Rodriguez-Franco, M.I. New tacrine-4-oxo-4H-chromene hybrids as multifunctional agents for the treatment of Alzheimer's disease, with cholinergic, Antioxidant, and β-amyloid-reducing. J. Med. Chem. 2012, 55, 1303-1317.
49. Galdeano, C.; Viayna, E.; Sola, I.; Formosa, X.; Camps, P.; Badia, A.; Clos, M.V.; Relat, J.; Ratia, M.; Bartolini, M.; et al. Huprine-tacrine heterodimers as anti-amyloidogenic compounds of potential interest against Alzheimer's and prion disease. J. Med. Chem. 2012, 55, 661-669.
50. 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. (Pubitemid 350309081)
51. Stetter, H.; Wulff, C. Über Verbindungen mit Urotropin-Struktur, XXIV1) Derivative des 1-Amino-adamantans. Chem. Ber. 1962, 95, 2302-2304.
52. Munch, H.; Hansen, J.S.; Pittelkow, M.; Christensen, J.B.; Boas, U. A new efficient synthesis of isothiocyanates from amines using di-tert-butyl dicarbonate. Tetrahedron Lett. 2008, 49, 3117-3119.
53. Ellman, G.L.; Courtney, K.D.; Andres, V.; Feather-Stone, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol. 1961, 7, 88-95.
54. Pohanka, M.; Jun, D.; Kuca, K. Improvement of acetylcholinesterase-based assay for organophosphates in way of identification by reactivators. Talanta. 2008, 77, 451-454.
55. Greig, N.H.; Utsuki, T.; Yu, Q.; Zhu, X.; Holloway, H.W.; Perry, T.; Lee, B.; Ingram, D.K.; Lahiri, D.K. A new therapeutic target in Alzheimer's disease treatment: Attention to butyrylcholinesterase. Curr. Med. Res. Opin. 2001, 17, 159-165. (Pubitemid 34003119)
56. Harel, M.; Schalk, I.; Ehret-Sabatier, L.; Bouet, F.; Goeldner, M.; Hirth, C.; Axelsen, P.H.; Silman, I.; Sussman, J.L. Quaternary ligand binding to aromatic residues in the active-site gorge of acetylcholinesterase. Proc. Natl. Acad. Sci. USA 1993, 90, 9031-9035. (Pubitemid 23306445)
57. Rydberg, E.H.; Brumshtein, B.; Greenblatt, H.M.; Wong, D.M.; Shaya, D.; Williams, L.D.; Carlier, P.R.; Pang, Y.P.; Silman, I.; Sussman, J.L. Complexes of alkylene-liked tacrine dimers with Torpedo california acetylcholinesterase: Binding of Bis(5)-tacrine produces a dramatic rearrangement in the active-site gorge. J. Med. Chem. 2006, 49, 5491-5500. (Pubitemid 44373181)
58. Camps, P.; Formosa, X.; Galdeano, C.; Munoz-Torrero, D.; Ramirez, L.; Gomez, E.; Isambert, N.; Lavilla, R.; Badia, A.; Clos, M.V.; et al. Pyrano[3,2-c]quinoline-6-chlorotacrine hybrids as a novel family of acetylcholinesterase- and beta-amyloid-directed anti-Alzheimer compounds. J. Med. Chem. 2009, 52, 5365-5379.
59. Fernandez-Bachiller, M.I.; Perez, C.; Campillo, N.E.; Paez, J.A.; Gonzales-Munoz, G.C.; Usan, P.; Garcia-Palomero, E.; Lopez, M.G.; Villarroya, M.; Garcia, A.G.; et al. Tacrine-melatonin hybrids as multifunctional agents for Alzheimer's disease, with cholinergic, antioxidant, and neuroprotective properties. ChemMedChem 2009, 4, 828-841.
60. Haviv, H.; Wong, D.M.; Greenblatt, H.M.; Carlier, P.R.; Pang, Y.P.; Silman, I.; Sussman, J.L. Crystal packing mediates enantioselective ligand recognition at the peripheral site of acetylcholinesterase. J. Am. Chem. Soc. 2005, 127, 11029-11036. (Pubitemid 41129879)
61. Nicolet, Y.; Lockbridge, O.; Masson, P.; Fontecilla-Camps, J.C.; Nachon, F. Crystal structure of human butyrylcholinesterase and of its complexes with substrate and products. J. Biol. Chem. 2003, 278, 41141-41147. (Pubitemid 37280939)
62. Trott, O.; Olson, A.J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem. 2010, 31, 455-461.
63. Pettersen, E.F.; Goddard, T.D.; Huang, C.C.; Couch, G.S.; Greenblatt, D.M.; Meng, E.C.; Ferrin, T.E. UCSF Chimera - A visualization system for exploratory research and analysis. J. Comput. Chem. 2004, 25, 1605-1612.
64. Kryger, G.; Harel, M.; Giles, K.; Toker, L.; Velan, B.; Lazar, A.; Kronman, C.; Barak, D.; Ariel, N.; Shafferman, A.; et al. Structures of recombinant native and E202Q mutant human acetylcholinesterase complexed with the snake-venom toxin fasciculin-II. Acta Crystallogr. D Biol. Crystalogr. 2000, 56, 1385-1394.
65. DeLano, W.L. The PyMOL Molecular Graphics System. Available online: http://www.pymol.org (accessed on 1 January 2002).