Synthesis and biological evaluation of deferiprone-resveratrol hybrids as antioxidants, Aβ1–42aggregation inhibitors and metal-chelating agents for Alzheimer's disease

European Journal of Medicinal Chemistry

Volumn 127, Issue , 2017, Pages 174-186

  Xu, Ping ^a   Zhang, Minkui ^b   Sheng, Rong ^b   Ma, Yongmin ^a  

^a ZHEJIANG CHINESE MEDICAL UNIVERSITY   (China)

^b ZHEJIANG UNIVERSITY   (China)

Author keywords

3 hydroxypyridin 4 one; Antioxidant; Beta amyloid aggregation; Metal chelator; Resveratrol derivatives

Indexed keywords

2 [2 (3 FLUOROPHENYL)VINYL] 5 HYDROXY 1 METHYL 1H PYRIDIN 4 ONE; 2 [2 (3 FLUOROPHENYL)VINYL] 5 HYDROXY 1H PYRIDIN 4 ONE; 2 [2 (3,5 DIHYDROXYPHENYL)VINYL] 5 HYDROXY 1 METHYL 1H PYRIDIN 4 ONE; 2 [2 (3,5 DIHYDROXYPHENYL)VINYL] 5 HYDROXY 1H PYRIDIN 4 ONE; 2 [2 (3,5 DIMETHOXYPHENYL)VINYL] 5 HYDROXY 1 METHYL 1H PYRIDIN 4 ONE; 2 [2 (3,5 DIMETHOXYPHENYL)VINYL] 5 HYDROXY 1H PYRIDIN 4 ONE; 2 [2 (4 CHLOROPHENYL)VINYL] 5 HYDROXY 1 METHYL 1H PYRIDIN 4 ONE; 2 [2 (4 CHLOROPHENYL)VINYL] 5 HYDROXY 1H PYRIDIN 4 ONE; 2 [2 (4 DIMETHYLAMINOPHENYL)VINYL] 5 HYDROXY 1 METHYL 1H PYRIDIN 4 ONE; 2 [2 (4 DIMETHYLAMINOPHENYL)VINYL] 5 HYDROXY 1H PYRIDIN 4 ONE; 2 [2 (4 ETHOXYPHENYL)VINYL] 5 HYDROXY 1 METHYL 1H PYRIDIN 4 ONE; 2 [2 (4 ETHOXYPHENYL)VINYL] 5 HYDROXY 1H PYRIDIN 4 ONE; 5 HYDROXY 1 METHYL 2 STYRYL 1H PYRIDIN 4 ONE; 5 HYDROXY 1 METHYL 2 [2 (4 NITROPHENYL)VINYL] 1H PYRIDIN 4 ONE; 5 HYDROXY 2 STYRYL 1H PYRIDIN 4 ONE; 5 HYDROXY 2 [2 (2 HYDROXYPHENYL)VINYL] 1 METHYL 1H PYRIDIN 4 ONE; 5 HYDROXY 2 [2 (2 HYDROXYPHENYL)VINYL] 1H PYRIDIN 4 ONE; 5 HYDROXY 2 [2 (2 METHOXYPHENYL)VINYL] 1 METHYL 1H PYRIDIN 4 ONE; 5 HYDROXY 2 [2 (2 METHOXYPHENYL)VINYL] 1H PYRIDIN 4 ONE; 5 HYDROXY 2 [2 (4 HYDROXYPHENYL)VINYL] 1 METHYL 1H PYRIDIN 4 ONE; 5 HYDROXY 2 [2 (4 HYDROXYPHENYL)VINYL] 1H PYRIDIN 4 ONE; 5 HYDROXY 2 [2 (4 NITROPHENYL)VINYL] 1H PYRIDIN 4 ONE; AMYLOID BETA PROTEIN[1-42]; ANTIOXIDANT; CHELATING AGENT; CURCUMIN; DEFERIPRONE; PROTEIN INHIBITOR; RESVERATROL; TROLOX C; UNCLASSIFIED DRUG; AMYLOID BETA PROTEIN; AMYLOID BETA-PROTEIN (1-42); COPPER; IRON; PEPTIDE FRAGMENT; PROTEIN AGGREGATE; PYRIDONE DERIVATIVE; STILBENE DERIVATIVE;

ABTS RADICAL SCAVENGING ASSAY; ALZHEIMER DISEASE; ANTIOXIDANT ACTIVITY; ARTICLE; CHELATION; CONTROLLED STUDY; DRUG DESIGN; DRUG SCREENING; DRUG STRUCTURE; DRUG SYNTHESIS; IC50; IN VITRO STUDY; MOLECULAR DOCKING; PROTEIN AGGREGATION; STOICHIOMETRY; STRUCTURE ACTIVITY RELATION; TRANSMISSION ELECTRON MICROSCOPY; ULTRAVIOLET SPECTROPHOTOMETRY; CHEMISTRY; DRUG EFFECTS; METABOLISM; PROTEIN SECONDARY STRUCTURE; SYNTHESIS;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANTIOXIDANTS; CHELATING AGENTS; CHEMISTRY TECHNIQUES, SYNTHETIC; COPPER; DRUG DESIGN; IRON; MOLECULAR DOCKING SIMULATION; PEPTIDE FRAGMENTS; PROTEIN AGGREGATES; PROTEIN STRUCTURE, SECONDARY; PYRIDONES; STILBENES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 85007579851     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2016.12.045     Document Type: Article

References (36)

1. [1] Alzheimer's, A., 2014 Alzheimer's disease facts and figures. Alzheimer's dementia 10 (2014), e47–92.
2. [2] Jakob-Roetne, R., Jacobsen, H., Alzheimer's disease: from pathology to therapeutic approaches. Angew. Chem. 48 (2009), 3030–3059.
3. [3] Reitz, C., Alzheimer's disease and the amyloid cascade hypothesis: a critical review. Int. J. Alzheimer's Dis., 2012, 2012, 369808.
4. [4] Darvesh, A.S., Carroll, R.T., Bishayee, A., Geldenhuys, W.J., Van der Schyf, C.J., Oxidative stress and Alzheimer's disease: dietary polyphenols as potential therapeutic agents. Expert Rev. Neurother. 10 (2010), 729–745.
5. [5] Hider, R.C., Ma, Y., Molina-Holgado, F., Gaeta, A., Roy, S., Iron chelation as a potential therapy for neurodegenerative disease. Biochem. Soc. Trans. 36 (2008), 1304–1308.
6. [6] Tomic, J.L., Pensalfini, A., Head, E., Glabe, C.G., Soluble fibrillar oligomer levels are elevated in Alzheimer's disease brain and correlate with cognitive dysfunction. Neurobiol. Dis. 35 (2009), 352–358.
7. [7] Pepeu, G., Giovannini, M.G., Cholinesterase inhibitors and beyond. Curr. Alzheimer Res. 6 (2009), 86–96.
8. [8] Hider, R.C., Roy, S., Ma, Y.M., Le Kong, X., Preston, J., The potential application of iron chelators for the treatment of neurodegenerative diseases. Metallomics 3 (2011), 239–249.
9. [9] Wang, P., Wang, Z.Y., Metal ions influx is a double edged sword for the pathogenesis of Alzheimer's disease. Ageing Res. Rev., 2016, 10.1016/j.arr.2016.10.003.
10. [10] Gaeta, A., Hider, R.C., The crucial role of metal ions in neurodegeneration: the basis for a promising therapeutic strategy. Br. J. Pharmacol. 146 (2005), 1041–1059.
11. [11] Lu, C., Guo, Y., Yan, J., Luo, Z., Luo, H.B., Yan, M., Huang, L., Li, X., Design, synthesis, and evaluation of multitarget-directed resveratrol derivatives for the treatment of Alzheimer's disease. J. Med. Chem. 56 (2013), 5843–5859.
12. [12] Ono, K., Condron, M.M., Ho, L., Wang, J., Zhao, W., Pasinetti, G.M., Teplow, D.B., Effects of grape seed-derived polyphenols on amyloid beta-protein self-assembly and cytotoxicity. Biol. Chem. 283 (2008), 32176–32187.
13. [13] Ho, L., Chen, L.H., Wang, J., Zhao, W., Talcott, S.T., Ono, K., Teplow, D., Humala, N., Cheng, A., Percival, S.S., Ferruzzi, M., Janle, E., Dickstein, D.L., Pasinetti, G.M., Heterogeneity in red wine polyphenolic contents differentially influences Alzheimer's disease-type neuropathology and cognitive deterioration. J. Alzheimer's Dis. Jad. 16 (2009), 59–72.
14. [14] Ono, K., Naiki, H., Yamada, M., The development of preventives and therapeutics for Alzheimer's disease that inhibit the formation of beta-amyloid fibrils (fAbeta), as well as destabilize preformed fAbeta. Curr. Pharm. Des. 12 (2006), 4357–4375.
15. [15] Wang, J., Ho, L., Zhao, W., Ono, K., Rosensweig, C., Chen, L., Humala, N., Teplow, D.B., Pasinetti, G.M., Grape-derived polyphenolics prevent Abeta oligomerization and attenuate cognitive deterioration in a mouse model of Alzheimer's disease. J. Neurosci. 28 (2008), 6388–6392.
16. [16] Zhou, T., Ma, Y., Kong, X., Hider, R.C., Design of iron chelators with therapeutic application. Dalton Trans. 41 (2012), 6371–6389.
17. [17] Maggio, A., D'Amico, G., Morabito, A., Capra, M., Ciaccio, C., Cianciulli, P., Di Gregorio, F., Garozzo, G., Malizia, R., Magnano, C., Mangiagli, A., Quarta, G., Rizzo, M., D'Ascola, D.G., Rizzo, A., Midiri, M., Deferiprone versus deferoxamine in patients with thalassemia major: a randomized clinical trial. Blood Cells, Mol. Dis. 28 (2002), 196–208.
18. [18] Gaeta, A., Molina-Holgado, F., Kong, X.L., Salvage, S., Fakih, S., Francis, P.T., Williams, R.J., Hider, R.C., Synthesis, physical-chemical characterisation and biological evaluation of novel 2-amido-3-hydroxypyridin-4(1H)-ones: iron chelators with the potential for treating Alzheimer's disease. Bioorg. Med. Chem. 19 (2011), 1285–1297.
19. [19] Liu, Z.D., Hider, R.C., Design of clinically useful iron(III)-selective chelators. Med. Res. Rev. 22 (2002), 26–64.
20. [20] Ma, Y., Xie, Y., Hider, R.C., A novel fluorescence method for determination of pFe3+. Analyst 138 (2013), 96–99.
21. [21] Sheng, R., Tang, L., Jiang, L., Hong, L.J., Shi, Y., Zhou, N.M., Hu, Y.Z., Novel 1-Phenyl-3-hydroxy-4-pyridinone derivatives as multifunctional agents for the therapy of Alzheimer's disease. Acs Chem. Neurosci. 7 (2016), 69–81.
22. [22] Schugar, H., Green, D.E., Bowen, M.L., Scott, L.E., Storr, T., Bohmerle, K., Thomas, F., Allen, D.D., Lockman, P.R., Merkel, M., Thompson, K.H., Orvig, C., Combating Alzheimer's disease with multifunctional molecules designed for metal passivation. Angew. Chem. 46 (2007), 1716–1718.
23. [23] Sharma, A.K., Pavlova, S.T., Kim, J., Kim, J., Mirica, L.M., The effect of Cu(2+) and Zn(2+) on the Abeta42 peptide aggregation and cellular toxicity. Metallomics 5 (2013), 1529–1536.
24. [24] Tycko, R., Progress towards a molecular-level structural understanding of amyloid fibrils. Curr. Opin. Struct. Biol. 14 (2004), 96–103.
25. [25] Prado-Prado, F., Garcia, I., Review of theoretical studies for prediction of neurodegenerative inhibitors. Mini-Rev. Med. Chem. 12 (2012), 452–466.
26. [26] 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. 50 (2007), 6446–6449.
27. [27] Ma, Y.M., Hider, R.C., The selective quantification of iron by hexadentate fluorescent probes. Bioorg. Med. Chem. 17 (2009), 8093–8101.
28. [28] Sharma, A.K., Kim, J., Prior, J.T., Hawco, N.J., Rath, N.P., Kim, J., Mirica, L.M., Small bifunctional chelators that do not disaggregate amyloid beta fibrils exhibit reduced cellular toxicity. Inorg. Chem. 53 (2014), 11367–11376.
29. [29] Jiang, L., Zhang, M.K., Tang, L., Weng, Q.J., Shen, Y.H., Hu, Y.Z., Sheng, R., Identification of 2-subsituted benzothiazole derivatives as triple-functional agents with potential for AD therapy. Rsc Adv. 6 (2016), 17318–17327.
30. [30] Sheng, R., Tang, L., Jiang, L., Hong, L., Shi, Y., Zhou, N., Hu, Y., Novel 1-Phenyl-3-hydroxy-4-pyridinone derivatives as multifunctional agents for the therapy of Alzheimer's disease. ACS Chem. Neurosci. 7 (2016), 69–81.
31. [31] Huang, L., Lu, C., Sun, Y., Mao, F., Luo, Z., Su, T., Jiang, H., Shan, W., Li, X., Multitarget-directed benzylideneindanone derivatives: anti-beta-amyloid (Abeta) aggregation, antioxidant, metal chelation, and monoamine oxidase B (MAO-B) inhibition properties against Alzheimer's disease. J. Med. Chem. 55 (2012), 8483–8492.
32. [32] Ma, Y., Roy, S., Kong, X., Chen, Y., Liu, D., Hider, R.C., Design and synthesis of fluorinated iron chelators for metabolic study and brain uptake. J. Med. Chem. 55 (2012), 2185–2195.
33. [33] Ma, Y., Luo, W., Quinn, P.J., Liu, Z., Hider, R.C., Design, synthesis, physicochemical properties, and evaluation of novel iron chelators with fluorescent sensors. J. Med. Chem. 47 (2004), 6349–6362.
34. [34] Piyamongkol, S., Ma, Y.M., Kong, X.L., Liu, Z.D., Aytemir, M.D., van der Helm, D., Hider, R.C., Amido-3-hydroxypyridin-4-ones as iron(III) ligands. Chemistry 16 (2010), 6374–6381.
35. [35] Liu, Z.D., Kayyali, R., Hider, R.C., Porter, J.B., Theobald, A.E., Design, synthesis, and evaluation of novel 2-substituted 3-hydroxypyridin-4-ones: structure-activity investigation of metalloenzyme inhibition by iron chelators. J. Med. Chem. 45 (2002), 631–639.
36. [36] Crescenzi, O., Tomaselli, S., Guerrini, R., Salvadori, S., D'Ursi, A.M., Temussi, P.A., Picone, D., Solution structure of the Alzheimer amyloid beta-peptide (1-42) in an apolar microenvironment-Similarity with a virus fusion domain. Eur. J. Biochem. 269 (2002), 5642–5648.