Design, synthesis and biological evaluation of edaravone derivatives bearing the N-benzyl pyridinium moiety as multifunctional anti-Alzheimer’s agents

References

• Karantzoulis S, Galvin JE. Distinguishing Alzheimer’s disease from other major forms of dementia. Expert Rev Neurother 2011;11:1579–91.
   PubMed Web of Science ®Google Scholar
• Alzheimer’s Association. 2019 Alzheimer’s disease facts and figures. Alzheimer’s Dement 2019;15:321–87.
   Web of Science ®Google Scholar
• Simunkova M, Alwasel SH, Alhazza IM, et al. Management of oxidative stress and other pathologies in Alzheimer’s disease. Arch. Toxicol 2019;93:2491–513.
   PubMed Web of Science ®Google Scholar
• World Health Organization. Dementia [online]. 2019. Available from: https://www.who.int/news-room/fact-sheets/detail/dementia
   Google Scholar
• Chopra K, Misra S, Kuhad A. Current perspectives on pharmacotherapy of Alzheimer’s disease. Expert Opin Pharmacother 2011;12:335–50.
   PubMed Web of Science ®Google Scholar
• Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med 2016;8:595–608.
   PubMed Web of Science ®Google Scholar
• Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 2002;297:353–6.
   PubMed Web of Science ®Google Scholar
• Kung HF. The β-amyloid hypothesis in Alzheimer’s disease: seeing is believing. ACS Med Chem Lett 2012;3:265–7.
   PubMed Web of Science ®Google Scholar
• Pimplikar SW. Reassessing the amyloid cascade hypothesis of Alzheimer’s disease. Int J Biochem Cell Biol 2009;41:1261–8.
   PubMed Web of Science ®Google Scholar
• Tramutola A, Lanzillotta C, Perluigi M, Butterfield DA. Butterfield, oxidative stress, protein modification and Alzheimer disease. Brain Res Bull 2017;133:88–96.
   PubMed Web of Science ®Google Scholar
• Lahiri DK, Farlow MR, Greig NH, Sambamurti K. Current drug targets for Alzheimer’s disease treatment. Drug Dev Res 2002;56:267–81.
   Web of Science ®Google Scholar
• Jalili-Baleh L, Babaei E, Abdpour S, et al. A review on flavonoid-based scaffolds as multi-target-directed ligands (MTDLs) for Alzheimer’s disease. Eur J Med Chem 2018;152:570–89.
   PubMed Web of Science ®Google Scholar
• Weinstock. Selectivity of cholinesterase inhibition. CNS Drugs 1999;12:307–23.
   Web of Science ®Google Scholar
• Lushchekina SV, Kots ED, Novichkova DA, et al. Role of acetylcholinesterase in β-amyloid aggregation studied by accelerated molecular dynamics. BioNanoSci 2017;7:396–402.
   Web of Science ®Google Scholar
• Belluti F, Bartolini M, Bottegoni G, et al. Benzophenone-based derivatives: a novel series of potent and selective dual inhibitors of acetylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation. Eur J Med Chem 2011;46:1682–93.
   PubMed Web of Science ®Google Scholar
• Semenov VE, Zueva IV, Mukhamedyarov MA, et al. 6-Methyluracil derivatives as bifunctional acetylcholinesterase inhibitors for the treatment of Alzheimer’s disease. ChemMedChem 2015;10:1863–74.
   PubMed Web of Science ®Google Scholar
• Huang WJ, Zhang X, Chen WW. Role of oxidative stress in Alzheimer’s disease. Biomed Rep 2016;4:519–22.
   PubMed Web of Science ®Google Scholar
• Cheignon C, Tomas M, Bonnefont-Rousselot D, et al. Oxidative stress and the amyloid beta peptide in Alzheimer’s disease. Redox Biol 2018;14:450–64.
   PubMed Web of Science ®Google Scholar
• Poprac P, Jomova K, Simunkova M, et al. Targeting free radicals in oxidative stress-related human diseases. Trends Pharmacol Sci 2017;38:592–607.
   PubMed Web of Science ®Google Scholar
• Kell DB. Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson’s, Huntington’s, Alzheimer’s, prions, bactericides, chemical toxicology and others as examples. Arch Toxicol 2010;84:825–89.
   PubMed Web of Science ®Google Scholar
• Butterfield DA. The 2013 SFRBM discovery award: selected discoveries from the butterfield laboratory of oxidative stress and its sequela in brain in cognitive disorders exemplified by Alzheimer disease and chemotherapy induced cognitive impairment, Free Radic. Free Radic Biol Med 2014;74:157–74.
   PubMed Web of Science ®Google Scholar
• Butterfield DA, Drake J, Pocernich C, Castegna A. Evidence of oxidative damage in Alzheimer’s disease brain: central role for amyloid beta-peptide. Trends Mol Med 2001;7:548–54.
   PubMed Web of Science ®Google Scholar
• Cai Z, Zhao B, Ratka A. Oxidative stress and β-amyloid protein in Alzheimer’s disease. Neuromolecular Med 2011;13:223–50.
   PubMed Web of Science ®Google Scholar
• Butterfield DA, Griffin S, Münch G, Pasinetti GM. Amyloid beta-peptide and amyloid pathology are central to the oxidative stress and inflammatory cascades under which Alzheimer’s disease brain exists. J Alzheimers Dis 2002;4:193–201.
   PubMed Web of Science ®Google Scholar
• Butterfield DA, Boyd-Kimball D. Redox proteomics and amyloid β-peptide: insights into Alzheimer disease. J Neurochem 2019;151:459–87.
   PubMed Web of Science ®Google Scholar
• Singh M, Kaur M, Chadha N, Silakari O. Hybrids: a new paradigm to treat Alzheimer’s disease. Mol Divers 2016;20:271–97.
   PubMed Web of Science ®Google Scholar
• Yiannopoulou KG, Papageorgiou SG. Current and future treatments for Alzheimer’s disease. Ther Adv Neurol Disord 2013;6:19–33.
   PubMed Web of Science ®Google Scholar
• Briggs R, Kennelly SP, O'Neill D. Drug treatments in Alzheimer’s disease. Clin Med (Lond) 2016;16:247–53.
   PubMed Web of Science ®Google Scholar
• Cavalli A, Bolognesi ML, Minarini A, et al. Multi-target-directed ligands to combat neurodegenerative diseases. J Med Chem 2008;51:347–72.
   PubMed Web of Science ®Google Scholar
• Unzeta M, Esteban G, Bolea I, et al. Multi-target directed donepezil-like ligands for Alzheimer’s disease. Front Neurosci 2016;10:1–24.
   PubMed Web of Science ®Google Scholar
• Qiang X, Li Y, Yang X, et al. DL-3-n-Butylphthalide-edaravone hybrids as novel dual inhibitors of amyloid-β aggregation and monoamine oxidases with high antioxidant potency for Alzheimer’s therapy. Bioorg Med Chem Lett 2017;27:718–22.
   PubMed Web of Science ®Google Scholar
• Kikuchi K, Kawahara KI, Uchikado H, et al. Potential of edaravone for neuroprotection in neurologic diseases that do not involve cerebral infarction. Exp Ther Med 2011;2:771–5.
   PubMed Web of Science ®Google Scholar
• Zhou S, Yu G, Chi L, et al. Neuroprotective effects of edaravone on cognitive deficit, oxidative stress and tau hyperphosphorylation induced by intracerebroventricular streptozotocin in rats. Neurotoxicology 2013;38:136–45.
   PubMed Web of Science ®Google Scholar
• Watanabe T, Tahara M, Todo S. The novel antioxidant edaravone: from bench to bedside. Cardiovasc Ther 2008;26:101–14.
   PubMed Web of Science ®Google Scholar
• Jiao S-S, Yao X-Q, Liu Y-H, et al. Edaravone alleviates Alzheimer’s disease-type pathologies and cognitive deficits. Proc Natl Acad Sci U S A 2015;112:5225–30.
   PubMed Web of Science ®Google Scholar
• Lan JS, Zhang T, Liu Y, et al. Design, synthesis and biological activity of novel donepezil derivatives bearing N-benzyl pyridinium moiety as potent and dual binding site acetylcholinesterase inhibitors. Eur J Med Chem 2017;133:184–96.
   PubMed Web of Science ®Google Scholar
• Alipour M, Khoobi M, Foroumadi A, et al. Novel coumarin derivatives bearing N-benzyl pyridinium moiety: Potent and dual binding site acetylcholinesterase inhibitors. Bioorg Med Chem 2012;20:7214–22.
   PubMed Web of Science ®Google Scholar
• Mollazadeh M, Mohammadi-Khanaposhtani M, Zonouzi A, et al. New benzyl pyridinium derivatives bearing 2,4-dioxochroman moiety as potent agents for treatment of Alzheimer’s disease: Design, synthesis, biological evaluation, and docking study. Bioorg Chem 2019;87:506–15.
   PubMed Web of Science ®Google Scholar
• Nadri H, Pirali-Hamedani M, Moradi A, et al. 5,6-Dimethoxybenzofuran-3-one derivatives: a novel series of dual acetylcholinesterase/butyrylcholinesterase inhibitors bearing benzyl pyridinium moiety. DARU J Pharm Sci 2013;21:1–9.
   Web of Science ®Google Scholar
• Baharloo F, Moslemin MH, Nadri H, et al. Benzofuran-derived benzylpyridinium bromides as potent acetylcholinesterase inhibitors. Eur J Med Chem 2015;93:196–201.
   PubMed Web of Science ®Google Scholar
• Chemical computing group. Molecular Operating Environment (MOE) Version 2015.10 [Online]. 2015. Available from: http://www.chemcomp.com
   Google Scholar
• Denya I, Malan SF, Enogieru AB, et al. Design, synthesis and evaluation of indole derivatives as multifunctional agents against Alzheimer’s disease. Medchemcomm 2018;9:357–70.
   PubMedGoogle Scholar
• Binda C, Li M, Hubalek F, et al. Insights into the mode of inhibition of human mitochondrial monoamine oxidase B from high-resolution crystal structures. Proc Natl Acad Sci U S A 2003;100:9750–5.
   PubMed Web of Science ®Google Scholar
• Ellman GL, Courtney KD, Andres V, Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 1961;7:88–95.
   PubMed Web of Science ®Google Scholar
• Timm M, Saaby L, Moesby L, Hansen EW. Considerations regarding use of solvents in in vitro cell based assays. Cytotechnology 2013;65:887–94.
   PubMed Web of Science ®Google Scholar
• Cotelle N, Bernier JL, Catteau JP, et al. Antioxidant properties of hydroxy-flavones. Free Radic Biol Med 1996;20:35–43.
   PubMed Web of Science ®Google Scholar
• Brand-Williams W, Cuvelier ME, Berset C, Leben-Wiss W. Use of a free radical method to evaluate antioxidant activity. Technol Food Sci Technol 1995;28:25–30.
   Web of Science ®Google Scholar
• Teponnou GAK, Joubert J, Malan SF. Tacrine, trolox and tryptoline as lead compounds for the design and synthesis of multi-target agents for Alzheimer’s Disease Therapy. Open Med Chem J 2017;11:24–37.
   PubMedGoogle Scholar
• Liu H, Wang L, Lv M, et al. AlzPlatform: an Alzheimer’s disease domain-specific chemogenomics knowledgebase for polypharmacology and target identification research. J Chem Inf Model 2014;54:1050–60.
   PubMed Web of Science ®Google Scholar
• Xie X-Q, Chen J-Z, Billings EM. 3D structural model of the G-protein-coupled cannabinoid CB2 receptor. Proteins 2003;53:307–19.
   PubMed Web of Science ®Google Scholar
• Vladimir VN. The nature of statistical learning theory. 2nd ed. New York (NY): Springer; 1995. Chapter 5.6.
   Google Scholar
• Zhao YH, Abraham MH, Ibrahim A, et al. Predicting penetration across the blood-brain barrier from simple descriptors and fragmentation schemes. J Chem Inf Model 2007;47:170–5.
   PubMed Web of Science ®Google Scholar
• De Ferrari GV, Canales MA, Shin I, et al. A structural motif of acetylcholinesterase that promotes amyloid beta-peptide fibril formation. Biochemistry 2001;40:10447–57.
   PubMed Web of Science ®Google Scholar
• Leong SW, Abas F, Lam KW, et al. 2-Benzoyl-6-benzylidenecyclohexanone analogs as potent dual inhibitors of acetylcholinesterase and butyrylcholinesterase. Bioorg Med Chem 2016;24:3742–51.
   PubMed Web of Science ®Google Scholar
• Castro A, Martinez A. Peripheral and dual binding site acetylcholinesterase inhibitors: implications in treatment of Alzheimer’s disease. Mini Rev Med Chem 2001;1:267–72.
   PubMed Web of Science ®Google Scholar
• Pakaski M, Rakonczay Z, Kasa P. Reversible and irreversible acetylcholinesterase inhibitors cause changes in neuronal amyloid precursor protein processing and protein kinase C level in vitro. Neurochem Int 2001;38:219–26.
   PubMed Web of Science ®Google Scholar
• Tougu V. Acetylcholinesterase: mechanism of catalysis and inhibition. Curr Med Chem CNS Agents 2001;1:155–70.
   Google Scholar
• Watanabe K, Tanaka M, Yuki S, et al. How is edaravone effective against acute ischemic stroke and amyotrophic lateral sclerosis? J Clin Biochem Nutr 2018;62:20–38.
   PubMed Web of Science ®Google Scholar
• Pal S, Mareddy J, Devi NS. High speed synthesis of pyrazolones using microwave-assisted neat reaction technology. J Brazilian Chem Soc 2008;19:1207–14.
   Web of Science ®Google Scholar
• Ruiz DL, Albesa AG, Ponzinibbio A, et al. Solvent effects on tautomerics equilibria in β-ketonitriles: NMR and theoretical studies. J Phys Org Chem 2010;23:985–94.
   Web of Science ®Google Scholar
• Ohara K, Fujii A, Ichimura Y, et al. Kinetic study of radical-scavenging and vitamin E-regenerating actions of edaravone (3-Methyl-1-phenyl-2-pyrazolin-5-one). Bullet Chem Soc Jpn 2006;79:421–6.
   Web of Science ®Google Scholar
• Erturk AG, Omerustaoglu H. Synthesis and cytotoxic evaluation of some substituted 5-pyrazolones and their urea derivatives. Molecules 2020;25:900–20.
   Web of Science ®Google Scholar
• Cbligand.org. Blood–Brain Barrier Predictor [online]. 2009. Available from: https://www.cbligand.org/BBB/predictor.php
   Google Scholar
• Sugimoto H, Iimura Y, Yamanishi Y, Yamatsu K. Synthesis and anti-acetylcholinesterase activity of 1-benzyl-4-[(5,6-dimethoxy-1-indanon-2-yl)methyl]piperidine hydrochloride (E2020) and related compounds’. Bioorg Med Chem Lett 1992;2:871–6.
   Web of Science ®Google Scholar
• Tokumaru O, Shuto Y, Ogata K, et al. Dose-dependency of multiple free radical-scavenging activity of edaravone. J Surg Res 2018;228:147–53.
   PubMed Web of Science ®Google Scholar
• Mostofi M, Mohammadi Ziarani G, Mahdavi M, et al. Synthesis and structure-activity relationship study of benzofuran-based chalconoids bearing benzylpyridinium moiety as potent acetylcholinesterase inhibitors. Eur J Med Chem 2015;103:361–9.
   PubMed Web of Science ®Google Scholar
• Darvesh S, Hopkins DA, Geula C. Neurobiology of butyrylcholinesterase. Nat Rev Neurosci 2003;4:131–8.
   PubMed Web of Science ®Google Scholar
• Darvesh S, Reid GA, Martin E. E. Biochemical and histochemical comparison of cholinesterases in normal and Alzheimer brain tissues. Curr Alzheimer Res 2010;7:386–400.
   PubMed Web of Science ®Google Scholar
• Harel M, Sussman JL, Krejci E, et al. Conversion of acetylcholinesterase to butyrylcholinesterase: modeling and mutagenesis. Proc Natl Acad Sci U S A 1992;89:10827–31.
   PubMed Web of Science ®Google Scholar
• Liston DR, Nielsen JA, Villalobos A, et al. Pharmacology of selective acetylcholinesterase inhibitors: implications for use in Alzheimer’s disease. Eur J Pharmacol 2004;486:9–17.
   PubMed Web of Science ®Google Scholar
• Barclay LRC, Locke SJ, MacNeil JM. Autoxidation in micelles. Synergism of vitamin C with lipid-soluble vitamin E and water-soluble Trolox. Can J Chem 1985;63:366–74.
   Web of Science ®Google Scholar
• Watanabe K, Morinaka Y, Iseki K, et al. Structure-activity relationship of 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone). Redox Rep 2003;8:151–5.
   PubMed Web of Science ®Google Scholar
• Queiroz AN, Mendes APS, Leal MS, et al. Tautomerism and radical-scavenging activity of edaravone by DFT methods. J Comput Theor Nanosci 2010;7:153–6.
   Google Scholar