JOURNAL OF THE CZECH PHARMACEUTICAL SOCIETY AND THE SLOVAK PHARMACEUTICAL SOCIETY

Čes. slov. farm. 2012, 61(5):210-221

Tacrine and its derivatives in the therapy of Alzheimer's disease

Jan Korábečný1, Katarína Špilovská2, Ondřej Benek1, Kamil Musílek3, Ondřej Soukup1, Kamil Kuča4,*
1 Univerzita Obrany Hradec Králové, Fakulta vojenského zdravotnictví a Fakultní nemocnice Hradec Králové
2 Univerzita Obrany Hradec Králové, Fakulta vojenského zdravotnictví
3 Univerzita Hradec Králové, Přírodovědecká fakulta a Fakultní nemocnice Hradec Králové
4 Univerzita Obrany, Fakulta vojenského zdravotnictví, Centrum pokročilých studií a Fakultní nemocnice Hradec Králové

Cholinesterase inhibitors have beneficial effects on the cognitive, functional, and behavioural symptoms of Alzheimer's disease (AD). Up to date, they represent almost the only drugs approved by the U.S. Food and Drug Administration agency for AD treatment. The group involves donepezil, rivastigmine and galantamine. Apart from the above mentioned cholinesterase inhibitors, memantine is used for AD treatment as well acting as N-methyl-D-aspartate (NMDA) non-competitive antagonist. Tacrine (9-amino-1,2,3,4-tetrahydroacridine) was the first cholinesterase inhibitor approved for symptomatic AD treatment. However, its several side effects (hepatotoxicity and gastrointestinal discomfort) limited tacrine further use. Recently, novel tacrine analogues are extensively investigated in endeavour to find less toxic compounds with the "multi-target directed ligand" profile affecting more AD pathological mechanisms. The following study summarizes the knowledge of up to date published tacrine analogues, their structural aspects and biological properties. According to structural aspects, tacrine derivatives are divided into three groups, where they are discussed.

Keywords: Alzheimer's disease; tacrine and its derivatives; acetylcholinesterase; inhibitor

Received: August 13, 2012; Accepted: September 19, 2012; Published: May 1, 2012  Show citation

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Korábečný J, Špilovská K, Benek O, Musílek K, Soukup O, Kuča K. Tacrine and its derivatives in the therapy of Alzheimer's disease. Čes. slov. farm. 2012;61(5):210-221.
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    References

    1. Alzheimer's Association: 2012 Alzheimer's disease facts and figures. Alzheimers Dement. 2012; 8, 131-168. Go to original source... Go to PubMed...
    2. Chopra K., Misra S., Kuhad A. Current perspectives on pharmacotherapy of Alzheimer's disease. Expert Opin. Pharmacother. 2011; 12, 335-350. Go to original source... Go to PubMed...
    3. Launer L. J., Fratiglioni L., Andersen K., Breteler M. M. B., Copeland R. J. M., Dartiques J. F., Lobo A., Martinez-Lage J., Soininen H., Hofman A. Regional differences in the incidence of dementia in Europe: EURODEM collaborative analyses 1999. Collective authors of Alzheimer Europe organization: Dementia in Europe Yearbook: 2008, 20; 1-178.
    4. Weiner M. W., Aisen P. S., Clifford R. J. Jr., Jagust W. J., Trojanowski J. Q., Shaw L., Saykin A. J., Morris J. C., Cairns N., Beckett L. A., Toga A., Green R., Walter S., Soares H., Snyder P., Siemers E., Potter W., Cole P. E., Schmidt M. The Alzheimer's disease neuroimaging initiative: Progress report and future plans. Alzheimers Dement. 2010; 6, 202-211. Go to original source... Go to PubMed...
    5. Green R. C., Cupples L. A., Go R., Benke K. S., Edeki T., Griffith P. A., Williams M., Hipps Y., Graff-Radford N., Bachman D., Farrer L. A. MIRAGE Study Group. Risk of dementia among white and African-American relatives of patients with Alzheimer's disease. J. Am. Med. Assoc. 2002; 287, 329-336. Go to original source... Go to PubMed...
    6. Drtinová L., Pohanka M. Alzheimerova demence: aspekty současné farmakologické léčby. Čes. slov. Farm. 2011; 60, 219-228.
    7. Bartus R. T., Dean R. L., Beer B., Lippa A. S. The cholinergic hypothesis of geriatric memory dysfunction. Science 1982; 217, 408-414. Go to original source... Go to PubMed...
    8. Bartus R. T., Dean R. L., Goas J. A., Lippa A. S. Age-related changes in passive avoidance retention: modulation with dietary choline. Science 1980; 209, 301-303. Go to original source... Go to PubMed...
    9. Perry E. K., Tomlinson B. E., Blessed G., Perry R. H., Cross A. J., Crow T. T. Noradrenergic and cholinergic systems in senile dementia of Alzheimer type. Lancet 1981; 2, 8238-8249. Go to original source... Go to PubMed...
    10. Drachman D. A. Memory and cognitive function in man: does the cholinergic system have a specific role? Neurology 1977; 27, 783-790. Go to original source... Go to PubMed...
    11. 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. Go to original source... Go to PubMed...
    12. Davies P., Maloney A. J. F. Selective loss of central cholinergic neurones in Alzheimer's disease. Lancet 1976; 2, 1403. Go to original source... Go to PubMed...
    13. Perry E. K., Gibson P. H., Blessed G., Perry R. H., Tomlinson B. E. Neurotransmitter enzyme abnormalities in senile dementia. Choline acetyltransferase and glutamic acid decarboxylase activities in necropsy brain tissue. J. Neurol. Sci. 1977; 34, 247-265. Go to original source... Go to PubMed...
    14. Drachman D. A., Leavitt J. Human memory and the cholinergic system. Arch. Neurol. 1974; 30, 113-121. Go to original source... Go to PubMed...
    15. Bartus R. T., Dean R. L., Beer B., Lippa A. S. The cholinergic hypothesis of geriatric memory dysfunction. Science 1982; 217, 408-417. Go to original source... Go to PubMed...
    16. Albert A. The chemical and biological properties of acridines. Sci. Prog. 1949; 37, 418-434.
    17. Valenti P., Rampa A., Bisi A., Andrisano V., Cavrini V., Fin L., Buriani A., Giusti P. Acetylcholinesterase inhibition by tacrine analogues. Bioorg. Med. Chem. Lett. 1997; 7, 2599-2602. Go to original source...
    18. Lee N. Y., Choi H. O., Kang Y. S. The acetylcholinesterase inhibitors competitively inhibited an acetyl L-carnitine transport through the blood-brain barrier. Neurochem. Res. 2012; 37, 1499-1507. Go to original source... Go to PubMed...
    19. 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-beta-peptides into Alzheimer's fibrils: possible role of the peripheral site of the enzyme. Neuron. 1996; 16, 881-891. Go to original source... Go to PubMed...
    20. Recanatini M., Cavalli A., Belluti F., Piazzi L., Rampa A., Bisi A., Gobbi S., Valenti P., Andrisano V., Bartolini M., Cavrini V. SAR of 9-amino-1,2,3,4-tetrahydroacridine-based acetylcholinesterase inhibitors: Synthesis, enzyme inhibitory activity, QSAR, and structure-based CoMFA of tacrine analogues. J. Med. Chem. 2000; 43, 2007-2018. Go to original source... Go to PubMed...
    21. dos Santos Pisoni D., Sobieski da Costa J., Gamba D., Petzhold C. L., de Amorim Borges A. C., Ceschi M. A., Lunardi P., Saraiva Gonçalves C. A. Synthesis and AChE inhibitory activity of new chiral tetrahydroacridine analoques from terpenic cyclanones. Eur. J. Med. Chem. 2010; 45, 526-535.
    22. Hamuľakova S., Kristian P., Jun D., Kuca K., Imrich J., Danihel I., Bőhm S., Klika K. D. Synthesis, structure, and cholinergic effect of novel neuroprotective compounds bearing the tacrine pharmacophore. Heterocycles 2008; 76, 1219-1235. Go to original source...
    23. Marco-Contelles J., León R., de Los Ríos C., Guglietta A., Terencio J., López M. G., García A. G., Villarroya M. Novel multipotent tacrine-dihydropyridine hybrids with improved acetylcholinesterase inhibitory and neuroprotective activities as potential drugs for the treatment of Alzheimer's disease. J. Med. Chem. 2006; 49, 7607-7610. Go to original source... Go to PubMed...
    24. Marco-Contelles J., León R., de los Ríos C., Samadi A., Bartolini M., Andrisano V., Huertas O., Barril X., Luque F. J., Rodríguez-Franco M. I., López B., López M. G., García A. G., Carreiras Mdo. C., Villarroya M. Tacripyrines, the first tacrine-dihydropyridine hybrids, as multitarget-directed ligands for the treatment of Alzheimer's disease. J. Med. Chem. 2009; 52, 2724-2732. Go to original source... Go to PubMed...
    25. Samadi A., Valderas C., de los Ríos C., Bastida A., Chioua M., González-Lafuente L., Colmena I., Gandía L., Romero A., Del Barrio L., Martín-de-Saavedra M. D., López M. G., Villarroya M., Marco-Contelles J. Cholinergic and neuroprotective drugs for the treatment of Alzheimer and neuronal vascular diseases. II. Synthesis, biological assessment, and molecular modelling of new tacrine analogues from highly substituted 2-aminopyridine-3-carbonitriles. Bioorg. Med. Chem. 2011; 19, 122-133. Go to original source... Go to PubMed...
    26. Dejmek L. 7-MEOTA. Drugs Future 1990, 15, 126-129. Go to original source...
    27. Patocka J., Jun D., Kuca K. Possible role of hydroxylated metabolites of tacrine in drug toxicity and therapy of Alzheimer's disease. Curr. Drug Metab. 2008; 9, 332-335. Go to original source... Go to PubMed...
    28. 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 cholinestrase inhibitors in Alzhemeir disease. Bioorg. Med. Chem. Lett. 2010; 20, 6093-6095. Go to original source... Go to PubMed...
    29. Korabecny J., Musilek K., Holas O., Nepovimova E., Jun D., Zemek F., Opletalova V., Patocka J., Dohnal V., Nachon F., Hroudova J., Fisar Z., Kuca K. 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. Go to original source... Go to PubMed...
    30. Korabecny J., Musilek K., Zemek F., Horova A., Holas O., Nepovimova E., Opletalova V., Hroudova J., Fisar Z., Jung Y.-S., Kuca K. 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. Go to original source... Go to PubMed...
    31. Hroudova J., Fisar Z., Korabecny J., Kuca K. In vitro effects of acetylcholinesterase inhibitors and reactivators on Complex I of electron transport chain. Neuroendocrinol. Lett. 2011; 32, 259-263.
    32. Defaux J., Sala M., Formosa X., Galdeano C., Taylor M. C., Alobaid W. A., Kelly J. M., Wright C. W., Camps P., Muñoz- -Torrero D. Huprines as a new family of dual acting trypanocidal-antiplasmodial agents. Bioorg. Med. Chem. 2011; 19, 1702-1707. Go to original source... Go to PubMed...
    33. Vanlaer S., Voet A., Gielens C., De Maeyer M., Compernolle F. Bridged 5,6,7,8-tetrahydro-1,6-naphthyridines, analogues of huperzine A: Synthesis, modelling studies and evaluation as inhibitors of acetylcholinesterase. Eur. J. Org. Chem. 2009; 643-654. Go to original source...
    34. 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-Asymmetr. 1998; 9, 835-849. Go to original source...
    35. Ronco C., Jean L., Renard P.-Y. Improved synthetic pathway for the derivatization of huprine scaffold. Tetrahedron 2010; 66, 7399-7404. Go to original source...
    36. Camps P., El Achab R., Morral J., Muñoz-Torrero D., Badia A., Baños J. E., Vivas N. M., Barril X., Orozco M., Luque F. J. New tacrine-huperzine A hybrids (huprines): Highly potent tight-binding acetylcholinesterase inhibitors of interest for the treatment of Alzheimer's disease J. Med. Chem. 2000; 43, 4657-4666. Go to original source... Go to PubMed...
    37. 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. Go to original source... Go to PubMed...
    38. 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-linked tacrine dimers with Torpedo californica acetylcholinesterase: Binding of bis5-tacrine produces a dramatic rearrangement in the active-site gorge. J. Med. Chem. 2006; 49, 5491-5500. Go to original source... Go to PubMed...
    39. Yu H., Li W. M., Kan K. K., Ho J. M., Carlier P. R., Pang Y. P., Gu Z. M., Zhong Z., Chan K., Wang Y. T., Han Y. F. The physicochemical properties and the in vivo AChE inhibition of two potential anti-Alzheimer agents, bis(12)-hupyridone and bis(7)-tacrine. J. Pharm. Biomed. Anal. 2008; 46, 75-81. Go to original source... Go to PubMed...
    40. Li W., Xue J., Niu C., Fu H., Lam C. S., Luo J., Chan H. H., Xue H., Kan K. K., Lee N. T., Li C., Pang Y., Li M., Tsim K. W., Jiang H., Chen K., Li X., Han Y. Synergistic neuroprotection by bis(7)-tacrine via concurrent blockade of N-methyl-D-aspartate receptors and neuronal nitric-oxide synthase. Mol. Pharmacol. 2007; 71, 1258-1267. Go to original source... Go to PubMed...
    41. Li C., Carlier P. R., Ren H., Kan K. K., Hui K., Wang H., Li W., Li Z., Xiong K., Clement E. C., Xue H., Liu X., Li M., Pang Y., Han Y. Alkylene tether-length dependent gamma aminobutyric acid type A receptor competitive antagonism by tacrine dimers. Neuropharmacology 2007; 52, 436-443. Go to original source... Go to PubMed...
    42. Zhou L., Liu Y. W., Peoples R. W., Yang M., Tian X., Ai Y. X., Pang Y. P., Li Z. W., Han Y. F., Li C. Y. Mechanism of bis(7)-tacrine inhibition of GABA: activated current in cultured rat hippocampal neurons. Neuropharmacology 2009; 57, 33-40. Go to original source... Go to PubMed...
    43. 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. Go to original source...
    44. Wlodek S. T., Antosiewicz J., McCammon J. A., Straatsma T. P., Gilson M. K., Briggs J. M., Humblet C., Sussman J. L. Binding of tacrine and 6-chlorotacrine by acetylcholinesterase. Biopolymers 1996; 38, 109-117. Go to original source...
    45. Rosini M., Simoni E., Bartolini M., Cavalli A., Ceccarini L., Pascu N., McClymont D. W., Tarozzi A., Bolognesi M. L., Minarini A., Tumiatti V., Andrisano V., Mellor I. R., Melchiorre C. Inhibition of acetylcholinesterase, beta-amyloid aggregation, and NMDA receptors in Alzheimer's disease: a promising direction for the multi-target-directed ligands gold rush. J. Med. Chem. 2008; 51, 4381-4384. Go to original source... Go to PubMed...
    46. Alonso D., Dorronsoro I., Rubio L., Muñoz P., Garcia-Palomero E., Del Monte M., Bidon-Chanal A., Orozco M., Luque F. J., Castro A., Medina M., Martinez A. Donepezil-tacrine hybrid related derivatives as new dual binding site inhibitors of AChE. Bioorg. Med. Chem. 2005; 13, 6588-6597. Go to original source... Go to PubMed...
    47. Muñoz-Torrero D., Camps P. Dimeric and hybrid anti-Alzheimer drug candidates. Curr. Med. Chem. 2006; 13, 399-422. Go to original source... Go to PubMed...
    48. Carlier P. R., Du D. M., Han Y., Liu J., Pang Y. P. Potent, easily synthesized huperzine A-tacrine hybrid acetylcholinesterase inhibitors. Bioorg. Med. Chem. Lett. 1999; 9, 2335-2338. Go to original source... Go to PubMed...
    49. Musial A., Bajda M., Malawska B. Recent developments in cholinesterases inhibitors for Alzheimer's disease treatment. Curr. Med. Chem. 2007; 14, 2654-2679. Go to original source... Go to PubMed...
    50. Decker M. Recent advances in the development of hybrid molecules/designed multiple compounds with antiamnesic properties. Mini Rev. Med. Chem. 2007; 7, 221-229. Go to original source... Go to PubMed...
    51. Li W. M., Kan K. K., Carlier P. R., Pang Y. P., Han Y. F. East meets West in the search for Alzheimer's therapeutics - novel dimeric inhibitors from tacrine and huperzine A. Curr. Alzheimer Res. 2007; 4, 386-396. Go to original source... Go to PubMed...
    52. Jiang H., Luo X., Bai D. Progress in clinical, pharmacological, chemical and structural biological studies of huperzine A: a drug of traditional Chinese medicine origin for the treatment of Alzheimer's disease. Curr. Med. Chem. 2003; 10, 2231-2252. Go to original source... Go to PubMed...
    53. Fang L., Kraus B., Lehmann J., Heilmann J., Zhang Y., Decker M. Design and synthesis of tacrine-ferulic acid hybrids as multipotent anti-Alzheimer drug candidates. Bioorg. Med. Chem. Lett. 2008; 18, 2905-2909. Go to original source... Go to PubMed...
    54. Heilmann J., Calis I., Kirmizibekmez H., Schuhly W., Harput S., Sticher O. Radical scavenger activity of phenylethanoid glycosides in FMLP stimulated human polymorphonuclear leukocytes: structure-activity relationships. Planta Med. 2000; 66, 746-748. Go to original source... Go to PubMed...
    55. Yan J. J., Cho J. Y., Kim H. S., Kim K. L., Jung J. S., Huh S. O., Suh H. W., Kim Y. H., Song D. K. Protection against beta-amyloid peptide toxicity in vivo with long-term administration of ferulic acid. Br. J. Pharmacol. 2001; 133, 89-96. Go to original source... Go to PubMed...
    56. Davalos A., Gomez-Cordoves C., Bartolome B. Extending applicability of the oxygen radical absorbance capacity (ORAC fluorescein) assay. J. Agric. Food Chem. 2004; 52, 48-54. Go to original source... Go to PubMed...
    57. Pi R., Mao X., Chao X., Cheng Z., Liu M., Duan X., Ye M., Chen X., Mei Z., Liu P., Li W., Han Y. Tacrine-6-ferulic acid, a novel multifunctional dimer, inhibits amyloid-ββ-mediated Alzheimer's disease-associated pathogenesis in vitro and in vivo. PLoS One. 2012; 7, Epub. Go to original source... Go to PubMed...
    58. Fernández-Bachiller M. I., Pérez C., Campillo N. E., Páez J. A., González-Muñoz G. C., Usán P., García-Palomero E., López M. G., Villarroya M., García A. G., Martínez A., Rodríguez-Franco M. I. Tacrine-melatonin hybrids as multifunctional agents for Alzheimer's disease, with cholinergic, antioxidant, and neuroprotective properties. ChemMedChem. 2009; 4, 828-841. Go to original source... Go to PubMed...
    59. Nunomura R. J., Castellani X., Zhu P. I., Moreira G., Perry M. A., Smith J. Involvement of oxidative stress in Alzheimer disease. Neuropathol. Exp. Neurol. 2006; 65, 631-641. Go to original source... Go to PubMed...
    60. Reiter R. J., Tan D.-X., Manchester L. C., Terron M. P., Flores L. J., Koppisepi S. Medical implications of melatonin: receptor-mediated and receptor-independent actions. Adv. Med. Sci. 2007; 52, 11-28.
    61. Masilamoni J. G., Jesudason E. P., Dhandayuthapani S., Ashok B. S., Vignesh S., Jebaraj W. C., Paul S. F., Jayakumar R. The neuroprotective role of melatonin against amyloid beta peptide injected mice. Free Radical. Res. 2008; 42, 661-673. Go to original source... Go to PubMed...
    62. Rodríguez-Franco M. I., Fernández-Bachiller M. I., Pérez C., Hernández-Ledesma B., Bartolomé B. Novel tacrine-melatonin hybrids as dual-acting drugs for Alzheimer disease, with improved acetylcholinesterase inhibitory and antioxidant properties. J. Med. Chem. 2006; 49, 459-462. Go to original source... Go to PubMed...
    63. Lysko P. G., Lysko K. A., Webb C. L., Feuerstein G., Mason P. E., Walter M. F., Mason R. P. Neuroprotective activities of carvedilol and a hydroxylated derivative: role of membrane biophysical interactions. Biochem. Pharmacol. 1998; 56, 1645-1656. Go to original source... Go to PubMed...
    64. Rosini M., Simoni E., Bartolini M., Cavalli A., Ceccarini L., Pascu N., McClymont D. W., Tarozzi A., Bolognesi M. L., Minarini A., Tumiatti V., Andrisano V., Mellor I. R., Melchiorre C. Inhibition of acetylcholinesterase, beta-amyloid aggregation, and NMDA receptors in Alzheimer's disease: a promising direction for the multi-target-directed ligands gold rush. J. Med. Chem. 2008; 51, 4381-4384. Go to original source... Go to PubMed...
    65. Malinski T. Nitric oxide and nitroxidative stress in Alzheimer's disease. J. Alzheimers Dis. 2007; 11, 207-218. Go to original source... Go to PubMed...
    66. Fang L., Appenroth D., Decker M., Kiehntopf M., Lupp A., Peng S., Fleck C., Zhang Y., Lehmann J. NO-donating tacrine hybrid compounds improve scopolamine-induced cognition impairment and show less hepatotoxicity. J. Med. Chem. 2008; 51, 7666-7669. Go to original source... Go to PubMed...
    67. Elsinghorst P. W., Cieslik J. S., Mohr K., Tränkle C., Gütschow M. First gallamine-tacrine hybrid: design and characterization at cholinesterases and the M2 muscarinic receptor. J. Med. Chem. 2007; 50, 5685-5695. Go to original source... Go to PubMed...
    68. Camps P., Formosa X., Galdeano C., Gómez T., Muñoz-Torrero D., Scarpellini M., Viayna E., Badia A., Clos M. V., Camins A., Pallàs M., Bartolini M., Mancini F., Andrisano V., Estelrich J., Lizondo M., Bidon-Chanal A., Luque F. J. Novel donepezil-based inhibitors of acetyl- and butyrylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation. J. Med. Chem. 2008; 51, 3588-3598. Go to original source... Go to PubMed...
    69. Camps P., Formosa X., Galdeano C., Muñoz-Torrero D., Ramírez L., Gómez E., Isambert N., Lavilla R., Badia A., Clos M. V., Bartolini M., Mancini F., Andrisano V., Arce M. P., Rodríguez-Franco M. I., Huertas O., Dafni T., Luque F. J. 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. Go to original source... Go to PubMed...
    70. Morris M. C., Schneider J. A., Tangney C. C. Thoughts on B-vitamins and dementia. J. Alzheimers Dis. 2006; 9, 429-433. Go to original source... Go to PubMed...
    71. Morris M. C., Evans D. A., Bienias J. L., Scherr P. A., Tangney C. C., Hebert L. E., Bennett D. A., Wilson R. S., Aggarwal N. Dietary niacin and the risk of incident Alzheimer's disease and of cognitive decline. J. Neurol. Neurosurg. Psychiatry. 2004; 75, 1093-1099. Go to original source... Go to PubMed...
    72. Szymański P., Markowicz M., Mikiciuk-Olasik E. Synthesis and biological activity of derivatives of tetrahydroacridine as acetylcholinesterase inhibitors. Bioorg. Chem. 2011; 39, 138-142. Go to original source... Go to PubMed...
    73. Galdeano C., Viayna E., Sola I., Formosa X., Camps P., Badia A., Clos M. V., Relat J., Ratia M., Bartolini M., Mancini F., Andrisano V., Salmona M., Minguillón C., González-Muñoz G. C., Rodríguez-Franco M. I., Bidon-Chanal A., Luque F. J., Muñoz-Torrero D. Huprine-tacrine heterodimers as anti-amyloidogenic compounds of potential interest against Alzheimer's and prion diseases. J. Med. Chem. 2012; 55, 661-669. Go to original source... Go to PubMed...
    74. Hamulakova S., Janovec L., Hrabinova M., Kristian P., Kuca K., Banasova M., Imrich J. 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. Go to original source... Go to PubMed...

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