Login Register Cart 0
Generic placeholder image

Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Research Article

Biological Evaluation of 8-Hydroxyquinolines as Multi-Target Directed Ligands for Treating Alzheimer’s Disease

Author(s): Damijan Knez, Izidor Sosič, Anja Pišlar, Ana Mitrović, Marko Jukič, Janko Kos and Stanislav Gobec*

Volume 16, Issue 9, 2019

Page: [801 - 814] Pages: 14

DOI: 10.2174/1567205016666191010130351

Price: $65

Abstract

Background: Accumulating evidence suggests that multi-target directed ligands have great potential for the treatment of complex diseases such as Alzheimer’s Disease (AD).

Objective: To evaluate novel chimeric 8-hydroxyquinoline ligands with merged pharmacophores as potential multifunctional ligands for AD.

Methods: Nitroxoline, PBT2 and compounds 2-4 were evaluated in-vitro for their inhibitory potencies on cathepsin B, cholinesterases, and monoamine oxidases. Furthermore, chelation, antioxidative properties and the permeability of Blood-Brain Barrier (BBB) were evaluated by spectroscopy-based assays and the inhibition of Amyloid β (Aβ) aggregation was determined in immunoassay. Cell-based assays were performed to determine cytotoxicity, neuroprotection against toxic Aβ species, and the effects of compound 2 on apoptotic cascade.

Results: Compounds 2-4 competitively inhibited cathepsin B β-secretase activity, chelated metal ions and were weak antioxidants. All of the compounds inhibited Aβ aggregation, whereas only compound 2 had a good BBB permeability according to the parallel artificial membrane permeability assay. Tested ligands 2 and 3 were not cytotoxic to SH-SY5Y and HepG2 cells at 10 μM. Compound 2 exerted neuroprotective effects towards Aβ toxicity, reduced the activation of caspase-3/7 and diminished the apoptosis of cells treated with Aβ1-42.

Conclusion: Taken together, our data suggest that compound 2 holds a promise to be used as a multifunctional ligand for AD.

Keywords: 8-hydroxyquinoline, PBT2, nitroxoline, multi-target directed ligands (MTDLs), Alzheimer’s disease, cathepsin B inhibition, metal chelation, neuroprotective activity.

« Previous Next »
[1]
Scheltens P, Blennow K, Breteler MM, de Strooper B, Frisoni GB, Salloway S, et al. Alzheimer’s disease. Lancet 388(10043): 505-17. (2016).
[http://dx.doi.org/10.1016/S0140-6736(15)01124-1] [PMID: 26921134]
[2]
Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer’s disease. Nat Rev Dis Primers 1: 15056. (2015).
[http://dx.doi.org/10.1038/nrdp.2015.56] [PMID: 27188934]
[3]
Zhang F, Jiang L. Neuroinflammation in Alzheimer’s disease. Neuropsychiatr Dis Treat 11: 243-56. (2015).
[http://dx.doi.org/10.2147/NDT.S75546] [PMID: 25673992]
[4]
Rodriguez-Vieitez E, Saint-Aubert L, Carter SF, Almkvist O, Farid K, Schöll M, et al. Diverging longitudinal changes in astrocytosis and amyloid PET in autosomal dominant Alzheimer’s disease. Brain 139(Pt 3): 922-36. (2016).
[http://dx.doi.org/10.1093/brain/awv404] [PMID: 26813969]
[5]
De Strooper B, Karran E. The cellular Phase of Alzheimer’s disease. Cell 164(4): 603-15. (2016).
[http://dx.doi.org/10.1016/j.cell.2015.12.056] [PMID: 26871627]
[6]
Jiang T, Sun Q, Chen S. Oxidative stress: a major pathogenesis and potential therapeutic target of antioxidative agents in Parkinson’s disease and Alzheimer’s disease. Prog Neurobiol 147: 1-19. (2016).
[http://dx.doi.org/10.1016/j.pneurobio.2016.07.005] [PMID: 27769868]
[7]
Bagheri S, Squitti R, Haertlé T, Siotto M, Saboury AA. Role of copper in the onset of Alzheimer’s disease compared to other metals. Front Aging Neurosci 9: 446. (2018).
[http://dx.doi.org/10.3389/fnagi.2017.00446] [PMID: 29472855]
[8]
Mathys ZK, White AR. Copper and Alzheimer’s disease. Adv Neurobiol 18: 199-216. (2017).
[http://dx.doi.org/10.1007/978-3-319-60189-2_10] [PMID: 28889269]
[9]
Ayton S, Lei P, Bush AI. Metallostasis in Alzheimer’s disease. Free Radic Biol Med 62: 76-89. (2013).
[http://dx.doi.org/10.1016/j.freeradbiomed.2012.10.558] [PMID: 23142767]
[10]
Šimić G, Babić Leko M, Wray S, Harrington CR, Delalle I, Jovanov-Milošević N, et al. Monoaminergic neuropathology in Alzheimer’s disease. Prog Neurobiol 151: 101-38. (2017).
[http://dx.doi.org/10.1016/j.pneurobio.2016.04.001] [PMID: 27084356]
[11]
Contestabile A. The history of the cholinergic hypothesis. Behav Brain Res 221(2): 334-40. (2011).
[http://dx.doi.org/10.1016/j.bbr.2009.12.044] [PMID: 20060018]
[12]
C Conley A. A Newhouse P. Advances in drug discovery and development in geriatric psychiatry. Curr Psychiatry Rep 20(2): 10. (2018).
[http://dx.doi.org/10.1007/s11920-018-0871-5] [PMID: 29504046]
[13]
Bawa P, Pradeep P, Kumar P, Choonara YE, Modi G, Pillay V. Multi-target therapeutics for neuropsychiatric and neurodegenerative disorders. Drug Discov Today 21(12): 1886-914. (2016).
[http://dx.doi.org/10.1016/j.drudis.2016.08.001] [PMID: 27506871]
[14]
Peters JU. Polypharmacology - foe or friend? J Med Chem 56(22): 8955-71. (2013).
[http://dx.doi.org/10.1021/jm400856t] [PMID: 23919353]
[15]
Mignani S, Huber S, Tomás H, Rodrigues J, Majoral JP. Why and how have drug discovery strategies in pharma changed? What are the new mindsets? Drug Discov Today 21(2): 239-49. (2016).
[http://dx.doi.org/10.1016/j.drudis.2015.09.007] [PMID: 26376356]
[16]
Gong CX, Liu F, Iqbal K. Multifactorial Hypothesis and Multi-Targets for Alzheimer’s Disease. J Alzheimers Dis 64(s1): S107-17. (2018).
[http://dx.doi.org/10.3233/JAD-179921] [PMID: 29562523]
[17]
Cavalli A, Bolognesi ML, Minarini A, Rosini M, Tumiatti V, Recanatini M, et al. Multi-target-directed ligands to combat neurodegenerative diseases. J Med Chem 51(3): 347-72. (2008).
[http://dx.doi.org/10.1021/jm7009364] [PMID: 18181565]
[18]
Oset-Gasque MJ, Marco-Contelles J. Alzheimer’s Disease, the “one-molecule, one-target” paradigm, and the multitarget directed ligand approach. ACS Chem Neurosci 9(3): 401-3. (2018).
[http://dx.doi.org/10.1021/acschemneuro.8b00069] [PMID: 29465220]
[19]
de Freitas Silva M, Dias KST, Gontijo VS, Ortiz CJC, Viegas C Jr. Multi-target directed drugs as a modern approach for drug design towards alzheimer’s disease: an update. Curr Med Chem 25(29): 3491-525. (2018).
[http://dx.doi.org/10.2174/0929867325666180111101843] [PMID: 29332563]
[20]
León R, Garcia AG, Marco-Contelles J. Recent advances in the multitarget-directed ligands approach for the treatment of Alzheimer’s disease. Med Res Rev 33(1): 139-89. (2013).
[http://dx.doi.org/10.1002/med.20248] [PMID: 21793014]
[21]
Bachurin SO, Bovina EV, Ustyugov AA. Drugs in clinical trials for Alzheimer’s disease: the major trends. Med Res Rev 37(5): 1186-225. (2017).
[http://dx.doi.org/10.1002/med.21434] [PMID: 28084618]
[22]
Ismaili L, Refouvelet B, Benchekroun M, Brogi S, Brindisi M, Gemma S, et al. Multitarget compounds bearing tacrine- and donepezil-like structural and functional motifs for the potential treatment of Alzheimer’s disease. Prog Neurobiol 151: 4-34. (2017).
[http://dx.doi.org/10.1016/j.pneurobio.2015.12.003] [PMID: 26797191]
[23]
Lanza V, Milardi D, Di Natale G, Pappalardo G. Repurposing of copper(II)-chelating drugs for the treatment of neurodegenerative diseases. Curr Med Chem 25(4): 525-39. (2018).
[http://dx.doi.org/10.2174/0929867324666170518094404] [PMID: 28521682]
[24]
Squitti R, Salustri C. Agents complexing copper as a therapeutic strategy for the treatment of Alzheimer’s disease. Curr Alzheimer Res 6(6): 476-87. (2009).
[http://dx.doi.org/10.2174/156720509790147133] [PMID: 19747159]
[25]
Johanssen T, Suphantarida N, Donnelly PS, Liu XM, Petrou S, Hill AF, et al. PBT2 inhibits glutamate-induced excitotoxicity in neurons through metal-mediated preconditioning. Neurobiol Dis 81: 176-85. (2015).
[http://dx.doi.org/10.1016/j.nbd.2015.02.008] [PMID: 25697105]
[26]
Crouch PJ, Savva MS, Hung LW, Donnelly PS, Mot AI, Parker SJ, et al. The Alzheimer’s therapeutic PBT2 promotes amyloid-β degradation and GSK3 phosphorylation via a metal chaperone activity. J Neurochem 119(1): 220-30. (2011).
[http://dx.doi.org/10.1111/j.1471-4159.2011.07402.x] [PMID: 21797865]
[27]
Adlard PA, Bica L, White AR, Nurjono M, Filiz G, Crouch PJ, et al. Metal ionophore treatment restores dendritic spine density and synaptic protein levels in a mouse model of Alzheimer’s disease. PLoS One 6(3)e17669 (2011).
[http://dx.doi.org/10.1371/journal.pone.0017669] [PMID: 21412423]
[28]
Grossi C, Francese S, Casini A, Rosi MC, Luccarini I, Fiorentini A, et al. Clioquinol decreases amyloid-beta burden and reduces working memory impairment in a transgenic mouse model of Alzheimer’s disease. J Alzheimers Dis 17(2): 423-40. (2009).
[http://dx.doi.org/10.3233/JAD-2009-1063] [PMID: 19363260]
[29]
Adlard PA, Cherny RA, Finkelstein DI, Gautier E, Robb E, Cortes M, et al. Rapid restoration of cognition in Alzheimer’s transgenic mice with 8-hydroxy quinoline analogs is associated with decreased interstitial Abeta. Neuron 59(1): 43-55. (2008).
[http://dx.doi.org/10.1016/j.neuron.2008.06.018] [PMID: 18614028]
[30]
Ryan TM, Roberts BR, McColl G, Hare DJ, Doble PA, Li QX, et al. Stabilization of nontoxic Aβ-oligomers: insights into the mechanism of action of hydroxyquinolines in Alzheimer’s disease. J Neurosci 35(7): 2871-84. (2015).
[http://dx.doi.org/10.1523/JNEUROSCI.2912-14.2015] [PMID: 25698727]
[31]
Lannfelt L, Blennow K, Zetterberg H, Ames D, Harrison J, Masters CL, et al. Safety, efficacy, and biomarker findings of PBT2 in targeting Abeta as a modifying therapy for Alzheimer’s disease: a phase IIa, double-blind, randomised, placebo-controlled trial. Lancet Neurol 7(9): 779-86. (2008).
[http://dx.doi.org/10.1016/S1474-4422(08)70167-4] [PMID: 18672400]
[32]
Huntington Study Group Reach2HD Investigators. Safety, tolerability, and efficacy of PBT2 in Huntington’s disease: a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Neurol 14(1): 39-47. (2015).
[http://dx.doi.org/10.1016/S1474-4422(14)70262-5] [PMID: 25467848]
[33]
Villemagne VL, Rowe CC, Barnham KJ, Cherny R, Woodward M, Bozinosvski S, et al. A randomized, exploratory molecular imaging study targeting amyloid β with a novel 8-OH quinoline in Alzheimer’s disease: The PBT2-204 IMAGINE study. Alzheimers Dement 3(4): 622-35. (2017).
[http://dx.doi.org/10.1016/j.trci.2017.10.001] [PMID: 29201996]
[34]
Langbehn DR. Criteria for success in safety and tolerability trials. Lancet Neurol 14(1): 24-5. (2015).
[http://dx.doi.org/10.1016/S1474-4422(14)70265-0] [PMID: 25467849]
[35]
Oliveri V, Vecchio G. 8-Hydroxyquinolines in medicinal chemistry: a structural perspective. Eur J Med Chem 120: 252-74. (2016).
[http://dx.doi.org/10.1016/j.ejmech.2016.05.007] [PMID: 27191619]
[36]
Prati F, Bergamini C, Fato R, Soukup O, Korabecny J, Andrisano V, et al. Novel 8-hydroxyquinoline derivatives as multitarget compounds for the treatment of Alzheimer’s disease. ChemMedChem 11(12): 1284-95. (2016).
[http://dx.doi.org/10.1002/cmdc.201600014] [PMID: 26880501]
[37]
Liang SH, Southon AG, Fraser BH, Soukup O, Korabecny J, Andrisano V, et al. Novel fluorinated 8-hydroxyquinoline based metal ionophores for exploring the metal hypothesis of Alzheimer’s disease. ACS Med Chem Lett 6(9): 1025-9. (2015).
[http://dx.doi.org/10.1021/acsmedchemlett.5b00281] [PMID: 26396692]
[38]
Wang L, Esteban G, Ojima M, Bautista-Aguilera OM, Inokuchi T, Moraleda I, et al. Donepezil + propargylamine + 8-hydroxyquinoline hybrids as new multifunctional metal-chelators, ChE and MAO inhibitors for the potential treatment of Alzheimer’s disease. Eur J Med Chem 80: 543-61. (2014).
[http://dx.doi.org/10.1016/j.ejmech.2014.04.078] [PMID: 24813882]
[39]
Wu MY, Esteban G, Brogi S, Shionoya M, Wang L, Campiani G, et al. Donepezil-like multifunctional agents: design, synthesis, molecular modeling and biological evaluation. Eur J Med Chem 121: 864-79. (2016).
[http://dx.doi.org/10.1016/j.ejmech.2015.10.001] [PMID: 26471320]
[40]
Mirković B, Markelc B, Butinar M, Mitrović A, Sosič I, Gobec S, et al. Nitroxoline impairs tumor progression in vitro and in vivo by regulating cathepsin B activity. Oncotarget 6(22): 19027-42. (2015).
[http://dx.doi.org/10.18632/oncotarget.3699] [PMID: 25848918]
[41]
Shim JS, Matsui Y, Bhat S, Nacev BA, Xu J, Bhang HE, et al. Effect of nitroxoline on angiogenesis and growth of human bladder cancer. J Natl Cancer Inst 102(24): 1855-73. (2010).
[http://dx.doi.org/10.1093/jnci/djq457] [PMID: 21088277]
[42]
Chang WL, Hsu LC, Leu WJ, Chen CS, Guh JH. Repurposing of nitroxoline as a potential anticancer agent against human prostate cancer: a crucial role on AMPK/mTOR signaling pathway and the interplay with Chk2 activation. Oncotarget 6(37): 39806-20. (2015).
[http://dx.doi.org/10.18632/oncotarget.5655] [PMID: 26447757]
[43]
Mirković B, Renko M, Turk S, Sosič I, Jevnikar Z, Obermajer N, et al. Novel mechanism of cathepsin B inhibition by antibiotic nitroxoline and related compounds. ChemMedChem 6(8): 1351-6. (2011).
[http://dx.doi.org/10.1002/cmdc.201100098] [PMID: 21598397]
[44]
Rawlings ND, Barrett AJ, Bateman A. MEROPS: the database of proteolytic enzymes, their substrates and inhibitors. Nucleic Acids Res 40(Database issue): D343-50. (2012).
[http://dx.doi.org/10.1093/nar/gkr987] [PMID: 22086950]
[45]
Klein DM, Felsenstein KM, Brenneman DE. Cathepsins B and L differentially regulate amyloid precursor protein processing. J Pharmacol Exp Ther 328(3): 813-21. (2009).
[http://dx.doi.org/10.1124/jpet.108.147082] [PMID: 19064719]
[46]
Andrew RJ, Kellett KA, Thinakaran G, Hooper NM. A greek tragedy: the growing complexity of Alzheimer amyloid precursor protein proteolysis. J Biol Chem 291(37): 19235-44. (2016).
[http://dx.doi.org/10.1074/jbc.R116.746032] [PMID: 27474742]
[47]
Lowry JR, Klegeris A. Emerging roles of microglial cathepsins in neurodegenerative disease. Brain Res Bull 139: 144-56. (2018).
[http://dx.doi.org/10.1016/j.brainresbull.2018.02.014] [PMID: 29454581]
[48]
Hook G, Yu J, Toneff T, Kindy M, Hook V. Brain pyroglutamate amyloid-β is produced by cathepsin B and is reduced by the cysteine protease inhibitor E64d, representing a potential Alzheimer’s disease therapeutic. J Alzheimers Dis 41(1): 129-49. (2014).
[http://dx.doi.org/10.3233/JAD-131370] [PMID: 24595198]
[49]
Hook V, Toneff T, Bogyo M, Greenbaum D, Medzihradszky KF, Neveu J, et al. Inhibition of cathepsin B reduces beta-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate beta-secretase of Alzheimer’s disease. Biol Chem 386(9): 931-40. (2005).
[http://dx.doi.org/10.1515/BC.2005.108] [PMID: 16164418]
[50]
Hook VY, Kindy M, Hook G. Inhibitors of cathepsin B improve memory and reduce beta-amyloid in transgenic Alzheimer disease mice expressing the wild-type, but not the Swedish mutant, beta-secretase site of the amyloid precursor protein. J Biol Chem 283(12): 7745-53. (2008).
[http://dx.doi.org/10.1074/jbc.M708362200] [PMID: 18184658]
[51]
Hook G, Hook V, Kindy M. The cysteine protease inhibitor, E64d, reduces brain amyloid-β and improves memory deficits in Alzheimer’s disease animal models by inhibiting cathepsin B, but not BACE1, β-secretase activity. J Alzheimers Dis 26(2): 387-408. (2011).
[http://dx.doi.org/10.3233/JAD-2011-110101] [PMID: 21613740]
[52]
Kindy MS, Yu J, Zhu H, El-Amouri SS, Hook V, Hook GR. Deletion of the cathepsin B gene improves memory deficits in a transgenic ALZHeimer’s disease mouse model expressing AβPP containing the wild-type β-secretase site sequence. J Alzheimers Dis 2012; 29(4): 827-40.
[http://dx.doi.org/10.3233/JAD-2012-111604] [PMID: 22337825]
[53]
Hook VY, Kindy M, Reinheckel T, Peters C, Hook G. Genetic cathepsin B deficiency reduces beta-amyloid in transgenic mice expressing human wild-type amyloid precursor protein. Biochem Biophys Res Commun 386(2): 284-8. (2009).
[http://dx.doi.org/10.1016/j.bbrc.2009.05.131] [PMID: 19501042]
[54]
Embury CM, Dyavarshetty B, Lu Y, Wiederin JL, Ciborowski P, Gendelman HE, et al. Cathepsin B improves ß-amyloidosis and learning and memory of Alzheimer’s Disease. J Neuroimmune Pharmacol 12(2): 340-52. (2017).
[http://dx.doi.org/10.1007/s11481-016-9721-6] [PMID: 27966067]
[55]
Mueller-Steiner S, Zhou Y, Arai H, Roberson ED, Sun B, Chen J, et al. Antiamyloidogenic and neuroprotective functions of cathepsin B: implications for Alzheimer’s disease. Neuron 51(6): 703-14. (2006).
[http://dx.doi.org/10.1016/j.neuron.2006.07.027] [PMID: 16982417]
[56]
Wang C, Sun B, Zhou Y, Grubb A, Gan L. Cathepsin B degrades amyloid-β in mice expressing wild-type human amyloid precursor protein. J Biol Chem 287(47): 39834-41. (2012).
[http://dx.doi.org/10.1074/jbc.M112.371641] [PMID: 23024364]
[57]
Sosič I, Mirković B, Arenz K, Stefane B, Kos J, Gobec S. Development of new cathepsin B inhibitors: combining bioisosteric replacements and structure-based design to explore the structure-activity relationships of nitroxoline derivatives. J Med Chem 56(2): 521-33. (2013).
[http://dx.doi.org/10.1021/jm301544x] [PMID: 23252745]
[58]
Sosič I, Mitrović A, Ćurić H, Knez D, Brodnik Žugelj H, Štefane B, et al. Cathepsin B inhibitors: Further exploration of the nitroxoline core. Bioorg Med Chem Lett 28(7): 1239-47. (2018).
[http://dx.doi.org/10.1016/j.bmcl.2018.02.042] [PMID: 29503024]
[59]
Kuhelj R, Dolinar M, Pungercar J, Turk V. The preparation of catalytically active human cathepsin B from its precursor expressed in Escherichia coli in the form of inclusion bodies. Eur J Biochem 229(2): 533-9. (1995).
[http://dx.doi.org/10.1111/j.1432-1033.1995.0533k.x] [PMID: 7744077]
[60]
Feng BY, Shoichet BK. A detergent-based assay for the detection of promiscuous inhibitors. Nat Protoc 1(2): 550-3. (2006).
[http://dx.doi.org/10.1038/nprot.2006.77] [PMID: 17191086]
[61]
Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7: 88-95. (1961).
[http://dx.doi.org/10.1016/0006-2952(61)90145-9] [PMID: 13726518]
[62]
Košak U, Knez D, Coquelle N, Brus B, Pišlar A, Nachon F, et al. N-Propargylpiperidines with naphthalene-2-carboxamide or naphthalene-2-sulfonamide moieties: Potential multifunctional anti-Alzheimer’s agents. Bioorg Med Chem 25(2): 633-45. (2017).
[http://dx.doi.org/10.1016/j.bmc.2016.11.032] [PMID: 27908752]
[63]
Zhou M, Panchuk-Voloshina N. A one-step fluorometric method for the continuous measurement of monoamine oxidase activity. Anal Biochem 253(2): 169-74. (1997).
[http://dx.doi.org/10.1006/abio.1997.2392] [PMID: 9367499]
[64]
Sharma OP, Bhat TK. DPPH antioxidant assay revisited. Food Chem 113(4): 1202-5. (2009).
[http://dx.doi.org/10.1016/j.foodchem.2008.08.008]
[65]
Knez D, Brus B, Coquelle N, Sosič I, Šink R, Brazzolotto X, et al. Structure-based development of nitroxoline derivatives as potential multifunctional anti-Alzheimer agents. Bioorg Med Chem 23(15): 4442-52. (2015).
[http://dx.doi.org/10.1016/j.bmc.2015.06.010] [PMID: 26116179]
[66]
Mao F, Yan J, Li J, Jia X, Miao H, Sun Y, et al. New multi-target-directed small molecules against Alzheimer’s disease: a combination of resveratrol and clioquinol. Org Biomol Chem 12(31): 5936-44. (2014).
[http://dx.doi.org/10.1039/C4OB00998C] [PMID: 24986600]
[67]
Lincoln KM, Richardson TE, Rutter L, Gonzalez P, Simpkins JW, Green KN. An N-heterocyclic amine chelate capable of antioxidant capacity and amyloid disaggregation. ACS Chem Neurosci 3(11): 919-27. (2012).
[http://dx.doi.org/10.1021/cn300060v] [PMID: 23173072]
[68]
Panek D, Więckowska A, Jończyk J, Godyń J, Bajda M, Wichur T, et al. Design, synthesis, and biological evaluation of 1-benzylamino-2-hydroxyalkyl derivatives as new potential disease-modifying multifunctional anti-Alzheimer’s agents. ACS Chem Neurosci 9(5): 1074-94. (2018).
[http://dx.doi.org/10.1021/acschemneuro.7b00461] [PMID: 29345897]
[69]
Murn J, Urleb U, Mlinaric-Rascan I. Internucleosomal DNA cleavage in apoptotic WEHI 231 cells is mediated by a chymotrypsin-like protease. Genes Cells 9(11): 1103-11. (2004).
[http://dx.doi.org/10.1111/j.1365-2443.2004.00794.x] [PMID: 15507121]
[70]
Barnham K, Gautier L, Kok G, Krippner G. 8-Hydroxy quinoline derivatives. US20080161353A1, 2008.
[71]
Kulshreshtha A, Piplani P. Current pharmacotherapy and putative disease-modifying therapy for Alzheimer’s disease. Neurol Sci 37(9): 1403-35. (2016).
[http://dx.doi.org/10.1007/s10072-016-2625-7] [PMID: 27250365]
[72]
Zemek F, Drtinova L, Nepovimova E, Sepsova V, Korabecny J, Klimes J, et al. Outcomes of Alzheimer’s disease therapy with acetylcholinesterase inhibitors and memantine. Expert Opin Drug Saf 13(6): 759-74. (2014).
[PMID: 24845946]
[73]
Spilovska K, Zemek F, Korabecny J, Nepovimova E, Soukup O, Windisch M, et al. Adamantane - a lead structure for drugs in clinical practice. Curr Med Chem 23(29): 3245-66. (2016).
[http://dx.doi.org/10.2174/0929867323666160525114026] [PMID: 27222266]
[74]
Ramsay RR, Majekova M, Medina M, Valoti M. Key targets for multi-target ligands designed to combat neurodegeneration. Front Neurosci 10: 375. (2016).
[http://dx.doi.org/10.3389/fnins.2016.00375] [PMID: 27597816]
[75]
Greig NH, Utsuki T, Ingram DK, Wang Y, Pepeu G, Scali C, et al. Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer beta-amyloid peptide in rodent. Proc Natl Acad Sci USA 102(47): 17213-8. (2005).
[http://dx.doi.org/10.1073/pnas.0508575102] [PMID: 16275899]
[76]
Ramsay RR. Molecular aspects of monoamine oxidase B. Prog Neuropsychopharmacol Biol Psychiatry 69: 81-9. (2016).
[http://dx.doi.org/10.1016/j.pnpbp.2016.02.005] [PMID: 26891670]
[77]
Sharma AK, Pavlova ST, Kim J, Kim J, Mirica LM. The effect of Cu(2+) and Zn(2+) on the Aβ42 peptide aggregation and cellular toxicity. Metallomics 5(11): 1529-36. (2013).
[http://dx.doi.org/10.1039/c3mt00161j] [PMID: 23995980]
[78]
Pelletier C, Prognon P, Bourlioux P. Roles of divalent cations and pH in mechanism of action of nitroxoline against Escherichia coli strains. Antimicrob Agents Chemother 39(3): 707-13. (1995).
[http://dx.doi.org/10.1128/AAC.39.3.707] [PMID: 7793877]
[79]
Sgarlata C, Arena G, Bonomo RP, Giuffrida A, Tabbì G. Simple and mixed complexes of copper(II) with 8-hydroxyquinoline derivatives and amino acids: Characterization in solution and potential biological implications. J Inorg Biochem 180: 89-100. (2018).
[http://dx.doi.org/10.1016/j.jinorgbio.2017.12.002] [PMID: 29247871]
[80]
Patel M. Targeting oxidative stress in central nervous system disorders. Trends Pharmacol Sci 37(9): 768-78. (2016).
[http://dx.doi.org/10.1016/j.tips.2016.06.007] [PMID: 27491897]
[81]
Shoji M, Kanai M. Cerebrospinal fluid Abeta40 and Abeta42: natural course and clinical usefulness. J Alzheimers Dis 3(3): 313-21. (2001).
[http://dx.doi.org/10.3233/JAD-2001-3306]
[82]
Findeis MA. The role of amyloid beta peptide 42 in Alzheimer’s disease. Pharmacol Ther 116(2): 266-86. (2007).
[http://dx.doi.org/10.1016/j.pharmthera.2007.06.006] [PMID: 17716740]
[83]
Savelieff MG, Lee S, Liu Y, Lim MH. Untangling amyloid-β, tau, and metals in Alzheimer’s disease. ACS Chem Biol 8(5): 856-65. (2013).
[http://dx.doi.org/10.1021/cb400080f] [PMID: 23506614]
[84]
Shankar GM, Li S, Mehta TH, Garcia-Munoz A, Shepardson NE, Smith I, et al. Amyloid-beta protein dimers isolated directly from Alzheimer’s brains impair synaptic plasticity and memory. Nat Med 14(8): 837-42. (2008).
[http://dx.doi.org/10.1038/nm1782] [PMID: 18568035]
[85]
Wolfe MS. Therapeutic strategies for Alzheimer’s disease. Nat Rev Drug Discov 1(11): 859-66. (2002).
[http://dx.doi.org/10.1038/nrd938] [PMID: 12415246]
[86]
Wang Z, Wang Y, Wang B, Li W, Huang L, Li X. Design, synthesis, and evaluation of orally available clioquinol-moracin m hybrids as multitarget-directed ligands for cognitive improvement in a rat model of neurodegeneration in Alzheimer’s disease. J Med Chem 58(21): 8616-37. (2015).
[http://dx.doi.org/10.1021/acs.jmedchem.5b01222] [PMID: 26473791]
[87]
Rankovic Z. CNS drug design: balancing physicochemical properties for optimal brain exposure. J Med Chem 58(6): 2584-608. (2015).
[http://dx.doi.org/10.1021/jm501535r] [PMID: 25494650]
[88]
Butterfield DA. Perspectives on oxidative stress in Alzheimer’s disease and predictions of future research emphases. J Alzheimers Dis 64(s1): S469-79. (2018).
[http://dx.doi.org/10.3233/JAD-179912] [PMID: 29504538]
[89]
Yang B, Sun X, Lashuel H, Zhang Y. Reactive oxidative species enhance amyloid toxicity in APP/PS1 mouse neurons. Neurosci Bull 28(3): 233-9. (2012).
[http://dx.doi.org/10.1007/s12264-012-1239-1] [PMID: 22622822]
[90]
Wang H, Ma J, Tan Y, Wang Z, Sheng C, Chen S, et al. Amyloid-beta1-42 induces reactive oxygen species-mediated autophagic cell death in U87 and SH-SY5Y cells. J Alzheimers Dis 21(2): 597-610. (2010).
[http://dx.doi.org/10.3233/JAD-2010-091207] [PMID: 20571221]
[91]
Awasthi A, Matsunaga Y, Yamada T. Amyloid-beta causes apoptosis of neuronal cells via caspase cascade, which can be prevented by amyloid-beta-derived short peptides. Exp Neurol 196(2): 282-9. (2005).
[http://dx.doi.org/10.1016/j.expneurol.2005.08.001] [PMID: 16137679]

Rights & Permissions Print Cite
Article Metrics
41
2
1
© 2024 Bentham Science Publishers | Privacy Policy