Design and synthesis of tacrine-phenothiazine hybrids as multitarget drugs for Alzheimer's disease

Medicinal Chemistry Research

Volumn 23, Issue 7, 2014, Pages 3546-3557

  Hui, Ai Ling ^a   Chen, Yan ^b   Zhu, Shi Jing ^a   Gan, Chang Sheng ^a   Pan, Jian ^a   Zhou, An ^c  

^a HEFEI UNIVERSITY OF TECHNOLOGY   (China)

^b ANHUI UNIVERSITY   (China)

^c ANHUI UNIVERSITY OF CHINESE MEDICINE   (China)

Author keywords

Acetylcholinesterase inhibitor (AChEI); Alzheimer's disease; Beta amyloid; Tacrine phenothiazine hybrids; Tau phosphorylation

Indexed keywords

1 (10H PHENOTHIAZIN 10 YL) 2 [4 (5,6,7,8 TETRAHYDROACRIDIN 9 YL) PIPERAZIN 1 YL]ETHANONE; 1 (10H PHENOTHIAZIN 10 YL) 2 [6 (5,6,7,8 TETRAHYDROACRIDIN 9 YLAMINO)HEXYLAMINO]ETHANONE; 1 (10H PHENOTHIAZIN 10 YL) 4 [4 (5,6,7,8 TETRAHYDROACRIDIN 9 YLAMINO) BUTYLAMINO]BUTAN 1 ONE; 2,2' [6 (5,6,7,8 TETRAHYDROACRIDIN 9 YLAMINO)HEXYLAZANEDIYL]BIS[1 (10H PHENOTHIAZIN 10YL)ETHANONE; 4,4' [4 (5,6,7,8 TETRAHYDROACRIDIN 9 YLAMINO)BUTYLAZANEDIYL)BIS[1 (10H PHENOTHIAZIN 10 YL)BUTAN 1 ONE; ACETYLCHOLINESTERASE; AMYLOID BETA PROTEIN; ENZYME INHIBITOR; OKADAIC ACID; PHENOTHIAZINE; TACRINE; TAU PROTEIN; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ARTICLE; BIOLOGICAL ACTIVITY; DRUG DESIGN; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; IC 50; PHYSICAL CHEMISTRY; SURFACE PLASMON RESONANCE;

EID: 84902385859     PISSN: 10542523     EISSN: 15548120     Source Type: Journal    
DOI: 10.1007/s00044-014-0931-2     Document Type: Article

References (32)

1. Bajda M, Guzior N, Ignasik M, Malawska B (2011) Multi-target-directed ligands in Alzheimer's disease treatment. Curr Med Chem 18:4949-4975
2. Carlier PR, Han YF, Chow ES-H, Li CP-L, Wang H, Lieu TX, Wong HS, Pang Y-P (1997) Evaluation of short-tether bis-THA AChE inhibitors. A further test of the dual binding site hypothesis. Bioorg Med Chem 7:351-357 (Pubitemid 29117099)
3. Cavalli A, Bolognesi ML, Capsoni S, Andrisano V, Bartolini M, Margotti E, Cattaneo A, Recanatini M, Melchiorre C (2007) A small molecule targeting the multifactorial nature of Alzheimer's disease. Angew Chem Int Ed 46:3689-3692 (Pubitemid 46981250)
4. Cavalli A, BolognesiML, Minarini A, Rosini M, Tumiatti V, Recanatini M, Melchiorre C (2008) Multi-target-directed ligands to combated neurodegenerative diseases. J Med Chem 51:347-370
5. Chitranshi N, Gupta S, Tripathi PK, Seth PK (2013) New molecular scaffolds for the design of Alzheimer's acetylcholinesterase inhibitors identified using ligand and receptor-based virtual screening. Med Chem Res 22:2328-2345
6. Darvesh S, McDonald RS, Renwell A, Conrad S, Darvesh KV, Mataija D, Comez G, Caines A, Walsh R, Martin E (2005) Structure-activity relationships for inhibition of human cholinesterase's by alkyl amide phenothiazine derivative. Bioorg Med Chem 13:211-222 (Pubitemid 39575706)
7. Fernández-Bachiller MI, Pérez C, González- Muñoz GC, Conde S, López MG, Villarroya M, García AG, Rodríguez-Franco MI (2010) Novel tacrine-8-hydroxyquinoline hybrids as multifunctional agents for the treatment of Alzheimer's diseases, with neuroprotective, cholinergic, antioxidant, and copper-complexing properties. J Med Chem 53:4927-4937
8. Fu HJ, Li WM, Luo JL, Lee NTK, Li MT, Tsim KWK, Pang YP, Youdim MBH, Han YF (2008) Promising anti-Alzheimer's dimer bis(7)-tacrine reduces b-amyloid generation by directly inhibiting BACE-1 activity. Biochem Biophys Res Commun 366:631-636
9. Ghadami SA, Hossein-pour Z, Khodarahmi R, Ghobadi S, Adibi H (2013) Synthesis and in vitro characterization of some benzo thiazole and benzofuranone-derivatives for quantification of fibrillar aggregates and inhibition of amyloid-mediated peroxidase activity. Med Chem Res 22:115-126
10. Hanger DP, Anderton BH, Noble W (2009a) Tau phosphorylation: the therapeutic challenge for neurodegenerative disease. Trends Mol Med 15:112-119
11. Hanger DP, Seereeram A, Noble W (2009b) Mediators of Tau phosphorylation in the pathogenesis of Alzheimer's disease. Exp Rev Neurother 9:1647-1666
12. Hu MK, Wu LJ, Hsiao G, Yen MH (2002) Homodimeric tacrine congener's asacetylcholinesterase inhibitions. J Med Chem 45:2277-2282 (Pubitemid 34525807)
13. Kapkovα P, Alptüzün V, Frey P, Erciyas E, Holzgrabe U (2006) Search for dual function inhibitors for Alzheimer's disease: synthesis and biological activity of acetylcholinesterase inhibitors of pyridinium-type and their Ab fibril formation inhibition capacity. Bioorg Med Chem 14:472-478
14. Lee SK, Lee IH, Kim HJ, Chang GS, Chung JE, No KT (2003) The PreADME approach: web-based program for rapid prediction of physic-chemical, drug absorption and drug-like properties, Euro QSAR 2002 Designing drugs and crop protectants: processes, problems and solutions. Blackwell, Boston, pp 418-420
15. Li WM, Pi RB, Chan HHN, Fu HJ, Lee NTK, Tsang HW, Pu YM, Chang DC, Li CC, Luo JL, Xiong KM, Li ZW, Xue H, Carlier PR, Pang YP, Tsim KWK, Li MT, Han YF (2005) Novel dimeric acetylcholinesterase inhibitor bis(7)-tarcrine, but not donepezil, prevents glutamate-induced neuronal apoptosis by blocking N-methyl-D-aspartate receptors. J Biol Chem 280:18179-18188 (Pubitemid 41389063)
16. Luo JL, Li WM, Liu YW, Zhang W, Fu HJ, Lee NTK, Yu H, Pang YP, Huang PB, Xia J, Li ZW, Li CY, Han YF (2007) Novel dimer bis(7)-tacrine proton-dependently inhibits NMDA-activated currents. Biochem Biophys Res Commun 361:505-509 (Pubitemid 47187285)
17. Massoud F, Guathier S (2010) Update on the pharmacological treatment of Alzheimer's disease. Curr Neuropharmacol 8:69-80
18. Minarini A, Milelli A, Rumiatti V, Rosini M, Simoni E, Bolognesi ML, Andrisano V, Bartolini M, Motori E, Angeloni C, Hrelia S (2012) Cystamine-tacrine dimer: a new multi-target-directed ligand as potential therapeutic agent for Alzheimer's disease treatment. Neuropharmacology 62:997-1003
19. Morphy R, Rankovic Z (2009) Designing multiple ligands-medicinal chemistry strategies and challenges. Curr Pharm Des 15:587-600
20. O'Leary JC, Li QY, Marinec P, Blair LJ, Congdon EE, Johnson AG, Jinwal UK, Koren J, Jones JR, Kraft C, Peters M, Abisambra JF, Duff KE, Weeber EJ, Gestwick JE, Dickey CA (2010) Phen-thiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden. Mol Neurodegener 5:45-55
21. Ouberai M, Brannstrom K, Vestling M, Olofsson A, Dumy P, Chierici S, Garcia J (2011) Clicked tacrine conjugates as acetylcholinesterase and b-amyloid directed compounds. Org Biomol Chem 9(4):1140-1147
22. Pang Y-P, Quiram P, Jelaric T, Hong F, Brimijoin S (1996) Highly potent, selective, and low cost bis-tetrahydroaminacrine inhibitors of acetylcholinesterase: steps toward novel drugs for treating Alzheimer's disease. J Biol Chem 271:23646-23649
23. Rizzo S, Tarozzi A, Bartolini M, Costa GD, Bisi A, Gobbi S, Belluti F, Ligresti A, Allará M, Monti JP, Andrisano V, Marzo VD, Hrelia P, Rampa A (2012) 2-arylbenzofuran-based molecules as multipotent Alzheimer's disease modifying agents. Eur J Med Chem 58:519-532
24. Rosini M, Simoni E, Bartolini M, Cavalli A, Ceccarini L, Pascu N, McClymont DW, Tarozzi A, Bolognesi ML, Minarini A, Tumiatti V, Andrisano V, Mellor IR, Melchiorre C (2008) Inhibition of acetylcholinesterase, β-amyloid aggregation, and NMDA acceptors in Alzheimer's disease: a promising direction for the multi-target-directed ligands gold rush. J Med Chem 51:4381-4384
25. Sterling J, Herzig Y, Goren T, Finkelstein N, Lerner D, Goldenberg W, Miskolczi I, Molnar S, Rantal F, Tamas T, Toth G, Zagyva A, Zekany A, Lavian G, Gross A, Friedman R, Razin M, Huang W, Krais B, Chorev M, Youdim MB, Weinstock M (2002) Novel dual inhibitors of AChE and MAO derived from hydroxy aminoindan and phenethylamine as potential treatment for Alzheimer's disease. J Med Chem 45:5260-5279 (Pubitemid 35429165)
26. Su H (2011) Design and synthesis of dual-target-directed ligands as potential treatment for Alzheimer's disease. M.S. Thesis, Hefei University of Technology
27. Takashima A (2006) GSK-3β is essential in the pathogenesis of Alzheimer's disease. J Alzheimer Dis 9:309-317
28. Tang H, Zhao LZ, Zhao HT, Huang SL, Zhong SM, Qin JK, Chen ZF, Huang ZS, Liang H (2011) Hybrids of oxoisoaporphine-tacrine congener: novel acetylcholinesterase and acetylcholinesterase-induced β-amyloid aggregation inhibitors. Eur J Med Chem 46:4970-4979
29. Taniguchi S, Suzuki N, Masuda M, Hisanaga S, Iwatsubo T, Goedert M, Hasegawa M (2005) Inhibition of heparin-induced tau filament formation by phenothiazine, polyphenols, and porphyrins. J Biol Chem 280:7614-7623 (Pubitemid 40349654)
30. Tumiatti V, Milelli A, Minarini A, Rosini M, Bolognesi ML, Micco M, Andeisano V, Bartolini M, Mancini F, Recanatini M, Cavalli A, Melchiorre C (2008) Structure-activity relationships of acetylcholinesterase noncovalent inhibitors based on a polyamine backbone 4. Further investigation on the inner spacer. J MedChem 51:7308-7312
31. Yan Y, Liu Y, Sorci M, Belfort G, Lusthader JW, Yan SS, Wang C (2007) Surface Plasmon resonance and unclear magnetic resonance studies of ABAD-A beta interaction. Biochemistry 46:1724-1731
32. Zhu YP, Xiao K, Ma LP, Xiong B, Fu Y, Yu HP, Wang W, Wang X, Hu DY, Heng HL, Li JY, Gong Q, Chai Q, Tang XC, Zhang HY, Li J, Shen JK (2009) Design, synthesis and biological evaluation of novel dual inhibitors of acetylcholinesterase and β-secretase. Bioorg Med Chem 17:1600-1613