Novel NSAID-derived drugs for the potential treatment of Alzheimer’s disease

International Journal of Molecular Sciences

Volumn 17, Issue 7, 2016, Pages

  Cacciatore, Ivana ^a   Marinelli, Lisa ^a   Fornasari, Erika ^a   Cerasa, Laura S ^a   Eusepi, Piera ^a   Türkez, Hasan ^a,b   Pomilio, Cristina ^a,c   Reale, Marcella ^a   D’Angelo, Chiara ^a   Costantini, Erica ^a   Di Stefano, Antonio ^a  

^a UNIVERSITY OF CHIETI   (Italy)

^b ERZURUM TECHNICAL UNIVERSITY   (Turkey)

^c Chemistry Section   (Italy)

Author keywords

Alzheimer s disease; Anti inflammatory drugs; Lipoic acid; Neuroinflammation

Indexed keywords

(R) N (2 AMINOETHYL) 2 (2 FLUORO [1,11 BIPHENYL] 4 YL) PROPANAMIDE; (R) N (6 AMINOETHYL) 2 (2 FLUORO [1,11 BIPHENYL] 4 YL) PROPANAMIDE; (S) N (2 AMINOBUTYL) 2 (6 METHOXYNAPHTHALEN 2 YL) PROPANAMIDE; (S) N (6 AMINOBUTYL) 2 (6 METHOXYNAPHTHALEN 2 YL) PROPANAMIDE; 5 [(R) 1,2 DITHIOLAN 3 YL] N [2 [(R) 2 (2 FLUORO [1,11 BIPHENYL] 4YL)PROPANAMIDO]ETHYL] PENTANAMIDE; 5 [(R) 1,2 DITHIOLAN 3 YL] N [2 [(S) 2 (6 METHOXYNAPHTHALEN 2 YL)PROPANAMIDO]ETHYL] PENTANAMIDE; 5 [(R) 1,2 DITHIOLAN 3 YL] N [4 [(R) 2 (2 FLUORO [1,11 BIPHENYL] 4YL)PROPANAMIDO]BUTYL] PENTANAMIDE; 5 [(R) 1,2 DITHIOLAN 3 YL] N [4 [(S) 2 (6 METHOXYNAPHTHALEN 2 YL)PROPANAMIDO]BUTYL] PENTANAMIDE; 5 [(R) 1,2 DITHIOLAN 3 YL] N [6 [(R) 2 (2 FLUORO [1,11 BIPHENYL] 4YL)PROPANAMIDO]HEXYL] PENTANAMIDE; 5 [(R) 1,2 DITHIOLAN 3 YL] N [6 [(S) 2 (6 METHOXYNAPHTHALEN 2 YL)PROPANAMIDO]HEXYL] PENTANAMIDE; CYCLOOXYGENASE 2; FLURBIPROFEN; INTERLEUKIN 1BETA; NAPROXEN DERIVATIVE; NONSTEROID ANTIINFLAMMATORY AGENT; PHORBOL 13 ACETATE 12 MYRISTATE; REACTIVE OXYGEN METABOLITE; THIOCTIC ACID; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; AMYLOID BETA PROTEIN; AMYLOID BETA-PROTEIN (25-35); ANTIOXIDANT; NAPROXEN; PEPTIDE FRAGMENT; TUMOR NECROSIS FACTOR;

ALZHEIMER DISEASE; ANTIOXIDANT ACTIVITY; ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CHEMICAL STRUCTURE; CHEMOTHERAPY; CONTROLLED STUDY; DRUG STABILITY; DRUG SYNTHESIS; ENZYME STABILITY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; INTESTINE FLUID; MTT ASSAY; OXIDATIVE STRESS; PHARMACOKINETIC ASSAY; PLASMA; PROTEIN EXPRESSION; PROTON NUCLEAR MAGNETIC RESONANCE; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA EXTRACTION; STOMACH JUICE; THIN LAYER CHROMATOGRAPHY; U937 CELL LINE; CELL LINE; CELL SURVIVAL; CHEMISTRY; DRUG EFFECTS; GENE EXPRESSION; GENETICS; METABOLISM;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ANTIOXIDANTS; CELL LINE; CELL SURVIVAL; CYCLOOXYGENASE 2; DRUG STABILITY; FLURBIPROFEN; GENE EXPRESSION; HUMANS; INTERLEUKIN-1BETA; NAPROXEN; PEPTIDE FRAGMENTS; REACTIVE OXYGEN SPECIES; TETRADECANOYLPHORBOL ACETATE; THIOCTIC ACID; TUMOR NECROSIS FACTOR-ALPHA;

EID: 85016399133     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms17071035     Document Type: Article

References (50)

1. Praveen Rao, P.N.; Knaus, E.E. Evolution of non-steroidal anti-inflammatory drugs (NSAIDs): COX inhibition and beyond. J. Pharm. Pharm. Sci. 2008, 11, 81-110.
2. Flower, R.J. The development of COX-2 inhibitors. Nat. Drug Discov. Rev. 2003, 2, 179-191. [CrossRef] [PubMed]
3. Umar, A.; Steele, V.E.; Menter, D.G.; Hawk, E.T. Mechanisms of nonsteroidal anti-inflammatory drugs in cancer prevention. Semin. Oncol. 2016, 43, 65-77. [CrossRef] [PubMed]
4. Wang, J.; Tan, L.; Wang, H.-F.; Tan, C.-C.; Meng, X.-F.; Wang, C.; Tang, S.-W.; Yu, J.-T.: Anti-inflammatory drugs and risk of Alzheimer’s disease: An updated systematic review and meta-analysis. J. Alzheimers Dis. 2015, 44, 385-396. [PubMed]
5. Dumont, M.; Beal, M.F.: Neuroprotective strategies involving ROS in Alzheimer disease. Free Radic. Biol. Med. 2011, 51, 1014-1026. [CrossRef] [PubMed]
6. Lloret, A.; Fuchsberger, T.; Giraldo, E.; Viña, J.: Molecular mechanisms linking amyloid β toxicity and Tau hyperphosphorylation in Alzheimer’s disease. Free Radic. Biol. Med. 2015, 83, 186-191. [CrossRef] [PubMed]
7. Townsend, K.P.; Praticó, D.: Novel therapeutic opportunities for Alzheimer’s disease: Focus on nonsteroidal anti-inflammatory drugs. FASEB J. 2005, 19, 1592-1601. [CrossRef] [PubMed]
8. Gilgun-Sherki, Y.; Melamed, E.; Offen, D.: Anti-inflammatory drugs in the treatment of neurodegenerative diseases: Current state. Curr. Pharm. Des. 2006, 12, 3509-3519. [CrossRef] [PubMed]
9. Dinarello, C.A.: Anti-inflammatory agents: Present and future. Cell 2010, 140, 935-950. [CrossRef] [PubMed]
10. Gasparini, L.; Rusconi, L.; Xu, H.; Del Soldato, P.; Ongini, E.: Modulation of β-amyloid metabolism by non-steroidal anti-inflammatory drugs in neuronal cell cultures. J. Neurochem. 2004, 88, 337-348. [CrossRef] [PubMed]
11. Scheiman, J.M.: NSAID-induced gastrointestinal injury: A focused update for clinicians. J. Clin. Gastroenterol. 2016, 50, 5-10. [CrossRef] [PubMed]
12. Reines, S.A.; Block, G.A.; Morris, J.C.; Lines, C.; Riggs, G.; Holloway, R. Rofecoxib did not slow progression of dementia in patients with established Alzheimer’s disease. Evid. Based Med. 2004, 9, 148.[CrossRef]
13. Pinnen, F.; Sozio, P.; Cacciatore, I.; Cornacchia, C.; Mollica, A.; Iannitelli, A.; D’Aurizio, E.; Cataldi, A.; Zara, S.; Nasuti, C. et al. Ibuprofen and glutathione conjugate as a potential therapeutic agent for treating Alzheimer’s disease. Arch. Pharm. 2011, 344, 139-148. [CrossRef] [PubMed]
14. Sozio, P.; Marinelli, L.; Cacciatore, I.; Fontana, A.; Türkez, H.; Giorgioni, G.; Ambrosini, D.; Barbato, F.; Grumetto, L.; Pacella, S. et al. New flurbiprofen derivatives: Synthesis, membrane affinity and evaluation of in vitro effect on β-amyloid levels. Molecules 2013, 18, 10747-10767. [CrossRef] [PubMed]
15. Sozio, P.; D’Aurizio, E.; Iannitelli, A.; Cataldi, A.; Zara, S.; Cantalamessa, F.; Nasuti, C.; di Stefano, A.: Ibuprofen and lipoic acid diamides as potential codrugs with neuroprotective activity. Arch. Pharm. 2010, 343, 133-142. [CrossRef] [PubMed]
16. Bannwarth, B.; Lapicque, F.; Pehourcq, F.; Gillet, P.; Schaeverbeke, T.; Laborde, C.; Dehais, J.; Gaucher, A.; Netter, P. Stereoselective disposition of ibuprofen enantiomers in human cerebrospinal fluid. Br. J. Clin. Pharmacol. 1995, 40, 266-269. [CrossRef] [PubMed]
17. Thomas, T.; Nadackal, T.G.; Thomas, K. Aspirin and non-steroidal anti-inflammatory drugs inhibit amyloid-β aggregation. Neuroreport 2001, 12, 3263-3267. [CrossRef] [PubMed]
18. Kim, S.; Chang, W.E.; Kumar, R.; Klimov, D.K.: (S)-naproxen interferes with the assembly of Aβ oligomers implicated in Alzheimer’s disease. Biophys. J. 2011, 100, 2024-2032. [CrossRef] [PubMed]
19. Gasparini, L.; Ongini, E.; Wilcock, D.; Morgan, D.: Activity of flurbiprofen and chemically related anti-inflammatory drugs in models of Alzheimer’s disease. Brain Res. Rev. 2005, 48, 400-408. [CrossRef] [PubMed]
20. Tegeder, I.; Niederberger, E.; Israr, E.; Gühring, H.; Brune, K.; Euchenhofer, C.; Grösch, S.; Geisslinger, G. Inhibition of NF-κB and AP-1 activation by R-and S-flurbiprofen. FASEB J. 2001, 15, 595-597. [PubMed]
21. Morihara, T.; Chu, T.; Ubeda, O.; Beech, W.; Cole, G.M.: Selective inhibition of Aβ42 production by NSAID R-enantiomers. J. Neurochem. 2002, 83, 1009-1012. [CrossRef] [PubMed]
22. Maczurek, A.; Hager, K.; Kenklies, M.; Sharman, M.; Martins, R.; Engel, J.; Carlson, D.A.; Münch, G.: Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer’s disease. Adv. Drug Deliv. Rev. 2008, 60, 1463-1470. [CrossRef] [PubMed]
23. Melchiorre, C.; Bolognesi, M.L.; Minarini, A.; Rosini, M.; Tumiatti, V. Polyamines in drug discovery: From the universal template approach to the multitarget-directed ligand design strategy. J. Med. Chem. 2010, 53, 5906-5914. [CrossRef] [PubMed]
24. Koufaki, M.; Calogeropoulou, T.; Detsi, A.; Roditis, A.; Kourounakis, A.P.; Papazafiri, P.; Tsiakitzis, K.; Gaitanaki, C.; Beis, I.; Kourounakis, P.N. Novel potent inhibitors of lipid peroxidation with protective effects against reperfusion arrhythmias. J. Med. Chem. 2001, 44, 4300-4303. [CrossRef] [PubMed]
25. Harnett, J.J.; Auguet, M.; Viossat, I.; Dolo, C.; Bigg, D.; Chabrier, P.-E. Novel lipoic acid analogues that inhibit nitric oxide synthase. Bioorg. Med. Chem. Lett. 2002, 12, 1439-1442. [CrossRef]
26. Sozio, P.; Cerasa, L.S.; Laserra, S.; Cacciatore, I.; Cornacchia, C.; Di Filippo, E.S.; Fulle, S.; Fontana, A.; Di Crescenzo, A.; Grilli, M. et al. Memantine-sulfur containing antioxidant conjugates as potential prodrugs to improve the treatment of Alzheimer’s disease. Eur. J. Pharm. Sci. 2013, 49, 187-198. [CrossRef] [PubMed]
27. Thériault, P.; Elali, A.; Rivest, S.: The dynamics of monocytes and microglia in Alzheimer’s disease. Alzheimers Res. Ther. 2015, 7. [CrossRef] [PubMed]
28. Malm, T.; Koistinaho, M.; Muona, A.; Magga, J.; Koistinaho, J. The role and therapeutic potential of monocytic cells in Alzheimer’s disease. GLIA 2010, 58, 889-900. [CrossRef] [PubMed]
29. Auwerx, J. The human leukemia cell line, THP-1: A multifacetted model for the study of monocyte-macrophage differentiation. Experientia 1991, 47, 22-31. [CrossRef] [PubMed]
30. Chanput, W.; Peters, V.; Wichers, H. THP-1 and U937 cells. In The Impact of Food Bioactives on Health: In Vitro and Ex Vivo Models; Verhoeckx, K., Cotter, P., López-Expósito, I., Kleiveland, C., Lea, T., Mackie, A., Requena, T., Swiatecka, D.,Wichers, H., Eds.; Springer International Publishing: Cham, Switzerland, 2015; pp. 147-159.
31. Song, M.-G.; Ryoo, I.-G.; Choi, H.-Y.; Choi, B.-H.; Kim, S.-T.; Heo, T.-H.; Lee, J.Y.; Park, P.-H.; Kwak, M.-K. NRF2 signaling negatively regulates phorbol-12-myristate-13-acetate (PMA)-induced differentiation of human monocytic U937 cells into pro-inflammatory macrophages. PLoS ONE 2015, 10, e0134235. [CrossRef] [PubMed]
32. Verin, A.D.; Liu, F.; Bogatcheva, N.; Borbiev, T.; Hershenson, M.B.; Wang, P.; Garcia, J.G.N.: Role of Ras-dependent ERK activation in phorbol ester-induced endothelial cell barrier dysfunction. Am. J. Physiol. Lung Cell. Mol. Physiol. 2000, 279, L360-L370. [PubMed]
33. Heuking, S.; Adam-Malpel, S.; Sublet, E.; Iannitelli, A.; Stefano, A.D.; Borchard, G. Stimulation of human macrophages (THP-1) using Toll-like receptor-2 (TLR-2) agonist decorated nanocarriers. J. Drug Target. 2009, 17, 662-670. [CrossRef] [PubMed]
34. Barbieri, S.S.; Eligini, S.; Brambilla, M.; Tremoli, E.; Colli, S. Reactive oxygen species mediate cyclooxygenase-2 induction during monocyte to macrophage differentiation: Critical role of NADPH oxidase. Cardiovasc. Res. 2003, 60, 187-197. [CrossRef]
35. Woods, A.G.; Cribbs, D.H.; Whittemore, E.R.; Cotman, C.W. Heparan sulfate and chondroit in sulfate glycosaminoglycan attenuate β-amyloid(25-35) induced neurodegeneration in cultured hippocampal neurons. Brain Res. 1995, 30, 53-62. [CrossRef]
36. Pike, C.J.; Walencewicz-Wasserman, A.J.; Kosmoski, J.; Cribbs, D.H.; Glabe, C.G.; Cotman, C.W. Structure-activity analyses of β-amyloid peptides: Contributions of the β 25-35 region to aggregation and neuro toxicity. J. Neurochem. 1995, 64, 253-265. [CrossRef] [PubMed]
37. Clementi, M.E.; Marini, S.; Coletta, M.; Orsini, F.; Giardina, B.; Misiti, F. Aβ(31-35) and Aβ(25-35) fragments of amyloid β-protein induce cellular death through apoptotic signals: Role of the redox state of methionine-35. FEBS Lett. 2005, 579, 2913-2918. [CrossRef] [PubMed]
38. Behl, C.; Davis, J.B.; Lesley, R.; Schubert, D. Hydrogen peroxide mediates amyloid β-protein toxicity. Cell 1994, 77, 817-827. [CrossRef]
39. Hsu, H.-Y.; Wen, M.-H.: Lipopolysaccharide-mediated reactive oxygen species and signal transduction in the regulation of interleukin-1 gene expression. J. Biol. Chem. 2002, 277, 22131-22139. [CrossRef] [PubMed]
40. Rochette, L.; Ghibu, S.; Richard, C.; Zeller, M.; Cottin, Y.; Vergely, C. Direct and indirect antioxidant properties of α-lipoic acid and therapeutic potential. Mol. Nutr. Food Res. 2013, 57, 114-125. [CrossRef] [PubMed]
41. Cacciatore, I.; Fornasari, E.; Baldassarre, L.; Cornacchia, C.; Fulle, S.; Di Filippo, E.S.; Pietrangelo, T.; Pinnen, F. A potent (R)-α-bis-lipoyl derivative containing 8-hydroxyquinoline scaffold: Synthesis and biological evaluation of its neuroprotective capabilities in SH-SY5Y human neuroblastoma cells. Pharmaceuticals 2013, 6, 54-69. [CrossRef] [PubMed]
42. Chanput, W.; Mes, J.; Vreeburg, R.A.M.; Savelkoul, H.F.J.; Wichers, H.J.: Transcription profiles of LPS-stimulated THP-1 monocytes and macrophages: A tool to study inflammation modulating effects of food-derived compounds. Food Funct. 2010, 1, 254-261. [CrossRef] [PubMed]
43. Millucci, L.; Ghezzi, L.; Bernardini, G.; Santucci, A.: Conformations and biological activities of amyloid β peptide 25-35. Curr. Protein Pept. Sci. 2010, 11, 54-67. [CrossRef] [PubMed]
44. Cacciatore, I.; Caccuri, A.M.; Cocco, A.; de Maria, F.; Di Stefano, A.; Luisi, G.; Pinnen, F.; Ricci, G.; Sozio, P.; Turella, P. Potent isozyme-selective inhibition of human glutathione S-transferase A1-1 by a novel glutathione S-conjugate. Amino Acids 2005, 29, 255-261. [CrossRef] [PubMed]
45. Cacciatore, I.; Caccuri, A.M.; Di Stefano, A.; Luisi, G.; Nalli, M.; Pinnen, F.; Ricci, G.; Sozio, P. Synthesis and activity of novel glutathione analogues containing an urethane backbone linkage. Farmaco 2003, 58, 787-793. [CrossRef]
46. Borde, A.S.; Karlsson, E.M.; Andersson, K.; Björhall, K.; Lennernäs, H.; Abrahamsson, B.: Assessment of enzymatic prodrug stability in human, dog and simulated intestinal fluids. Eur. J. Pharm. Biopharm. 2012, 80, 630-637. [CrossRef] [PubMed]
47. Cacciatore, I.; Cornacchia, C.; Fornasari, E.; Baldassarre, L.; Pinnen, F.; Sozio, P.; Di Stefano, A.; Marinelli, L.; Dean, A.; Fulle, S. et al. A glutathione derivative with chelating and in vitro neuroprotective activities: synthesis, physicochemical properties, and biological evaluation. Chem. Med. Chem. 2013, 8, 1818-1829. [CrossRef] [PubMed]
48. Prigol, M.; Nogueira, C.W.; Zeni, G.; Bronze, M.R.; Costantino, L.: Physicochemical and biochemical profiling of diphenyl diselenide. Appl. Biochem. Biotechnol. 2013, 169, 885-893. [CrossRef] [PubMed]
49. Wang, A.M.; Doyle, M.V.; Mark, D.F. Quantification of mRNA by the polymerase chain reaction. Proc. Natl. Acad. Sci. USA 1989, 86, 9717-9721. [CrossRef] [PubMed]
50. -ΔΔCt method. Methods 2001, 25, 402-408. [CrossRef] [PubMed]