Privileged multi-target directed propargyl-tacrines combining cholinesterase and monoamine oxidase inhibition activities

References

• Prince M, Ali G-C, Guerchet M, et al. Recent global trends in the prevalence and incidence of dementia, and survival with dementia. Alzheimers Res Ther 2016;8:23. https://doi.org/10.1186/s13195-016-0188-8.
   PubMed Web of Science ®Google Scholar
• Lane CA, Hardy J, Schott JM. Alzheimer’s disease. Eur J Neurol 2018;25:59–70. https://doi.org/10.1111/ene.13439.
   PubMed Web of Science ®Google Scholar
• Zemek F, Drtinova L, Nepovimova E, et al. Outcomes of Alzheimer’s disease therapy with acetylcholinesterase inhibitors and memantine. Expert Opin Drug Saf 2014;13:759–74. https://doi.org/10.1517/14740338.2014.914168.
   PubMed Web of Science ®Google Scholar
• Grossberg GT, Manes F, Allegri RF, et al. The safety, tolerability, and efficacy of once-daily memantine (28 mg): a multinational, randomized, double-blind, placebo-controlled trial in patients with moderate-to-severe Alzheimer’s disease taking cholinesterase inhibitors. CNS Drugs 2013;27:469–78. https://doi.org/10.1007/s40263-013-0077-7.
   PubMed Web of Science ®Google Scholar
• Weller J, Budson A. Current understanding of Alzheimer’s disease diagnosis and treatment. F1000Res 2018;7:1161. https://doi.org/10.12688/f1000research.14506.1.
   Google Scholar
• Cummings JL. The impact of depressive symptoms on patients with Alzheimer disease. Alzheimer Dis Assoc Disord 2003;17:61–2. https://doi.org/10.1097/00002093-200304000-00001.
   PubMed Web of Science ®Google Scholar
• Lyketsos CG, Lopez O, Jones B, et al. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA 2002;288:1475–83. https://doi.org/10.1001/jama.288.12.1475.
   PubMed Web of Science ®Google Scholar
• Starkstein SE, Mizrahi R. Depression in Alzheimer’s disease. Expert Rev Neurother 2006;6:887–95. https://doi.org/10.1586/14737175.6.6.887.
   PubMedGoogle Scholar
• Tipton KF. 90 years of monoamine oxidase: some progress and some confusion. J Neural Transm (Vienna) 2018;125:1519–51. https://doi.org/10.1007/s00702-018-1881-5.
   PubMed Web of Science ®Google Scholar
• Nicotra A, Pierucci F, Parvez H, Senatori O. Monoamine oxidase expression during development and aging. Neurotoxicology 2004;25:155–65. https://doi.org/10.1016/S0161-813X(03)00095-0.
   PubMed Web of Science ®Google Scholar
• Ramsay RR. Molecular aspects of monoamine oxidase B. Prog Neuropsychopharmacol Biol Psychiatry 2016;69:81–9. https://doi.org/10.1016/j.pnpbp.2016.02.005.
   PubMed Web of Science ®Google Scholar
• Bautista-Aguilera ÓM, Hagenow S, Palomino-Antolin A, et al. Multitarget-directed ligands combining cholinesterase and monoamine oxidase inhibition with histamine H3R antagonism for neurodegenerative diseases. Angewandte Chem Int Ed 2017;56:12765–9. https://doi.org/10.1002/anie.201706072.
   PubMed Web of Science ®Google Scholar
• Bautista-Aguilera ÓM, Budni J, Mina F, et al. Contilisant, a tetratarget small molecule for Alzheimer’s disease therapy combining cholinesterase, monoamine oxidase inhibition, and H3R antagonism with S1R agonism profile. J Med Chem 2018;61:6937–43. https://doi.org/10.1021/acs.jmedchem.8b00848.
   PubMed Web of Science ®Google Scholar
• Weinreb O, Amit T, Bar-Am O, Youdim MBH. Ladostigil: a novel multimodal neuroprotective drug with cholinesterase and brain-selective monoamine oxidase inhibitory activities for Alzheimer’s disease treatment. Curr Drug Targets 2012;13:483–94. https://doi.org/10.2174/138945012799499794.
   PubMed Web of Science ®Google Scholar
• Weinstock M, Bejar C, Wang RH, et al. TV3326, a novel neuroprotective drug with cholinesterase and monoamine oxidase inhibitory activities for the treatment of Alzheimer’s disease. J Neural Transm Suppl 2000;60:157–69. https://doi.org/10.1007/978-3-7091-6301-6_10.
   PubMedGoogle Scholar
• Weinstock M, Gorodetsky E, Poltyrev T, et al. A novel cholinesterase and brain-selective monoamine oxidase inhibitor for the treatment of dementia comorbid with depression and Parkinson’s disease. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:555–61. https://doi.org/10.1016/S0278-5846(03)00053-8.
   PubMed Web of Science ®Google Scholar
• Weinreb O, Amit T, Bar-Am O, Youdim MBH. A novel anti-Alzheimer’s disease drug, ladostigil neuroprotective, multimodal brain-selective monoamine oxidase and cholinesterase inhibitor. Int Rev Neurobiol 2011;100:191–215. https://doi.org/10.1016/B978-0-12-386467-3.00010-8.
   PubMed Web of Science ®Google Scholar
• Sagi Y, Weinstock M, Youdim MBH. Attenuation of MPTP-induced dopaminergic neurotoxicity by TV3326, a cholinesterase-monoamine oxidase inhibitor. J Neurochem 2003;86:290–7. https://doi.org/10.1046/j.1471-4159.2003.01801.x.
   PubMed Web of Science ®Google Scholar
• Korábečný J, Nepovimová E, Cikánková T, et al. Newly developed drugs for Alzheimer’s disease in relation to energy metabolism, cholinergic and monoaminergic neurotransmission. Neuroscience 2018;370:191–206. https://doi.org/10.1016/j.neuroscience.2017.06.034.
   PubMed Web of Science ®Google Scholar
• 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 2013;33:139–89. https://doi.org/10.1002/med.20248.
   PubMed Web of Science ®Google Scholar
• Gallagher DA, Schrag, A. Impact of newer pharmacological treatments on quality of life in patients with Parkinson’s disease. CNS Drugs 2008;22:563–86. https://doi.org/10.2165/00023210-200822070-00003.
   PubMed Web of Science ®Google Scholar
• do Carmo Carreiras M, Ismaili L, Marco-Contelles J. Propargylamine-derived multi-target directed ligands for Alzheimer’s disease therapy. Bioorg Med Chem Lett 2020;30:126880. https://doi.org/10.1016/j.bmcl.2019.126880.
   PubMed Web of Science ®Google Scholar
• Youdim MB, Gross A, Finberg JP. Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B. Br J Pharmacol 2001;132:500–6. https://doi.org/10.1038/sj.bjp.0703826.
   PubMed Web of Science ®Google Scholar
• Weinreb O, Amit T, Bar-Am O, et al. Involvement of multiple survival signal transduction pathways in the neuroprotective, neurorescue and APP processing activity of rasagiline and its propargyl moiety. J Neural Transm Suppl 2006;70:457–65.
   Google Scholar
• Horak M, Holubova K, Nepovimova E, et al. The pharmacology of tacrine at N-methyl-d-aspartate receptors. Prog Neuropsychopharmacol Biol Psychiatry 2017;75:54–62. https://doi.org/10.1016/j.pnpbp.2017.01.003.
   PubMed Web of Science ®Google Scholar
• Recanatini M, Cavalli A, Belluti F, et al. SAR of 9-amino-1,2,3,4-tetrahydroacridine-based acetylcholinesterase inhibitors: synthesis, enzyme inhibitory activity, QSAR, and structure-based CoMFA of tacrine analogues. J Med Chem 2000;43:2007–18. https://doi.org/10.1021/jm990971t.
   PubMed Web of Science ®Google Scholar
• Kaniakova M, Korabecny J, Holubova K, et al. 7-phenoxytacrine is a dually acting drug with neuroprotective efficacy in vivo. Biochem Pharmacol 2021;186:114460. https://doi.org/10.1016/j.bcp.2021.114460.
   PubMed Web of Science ®Google Scholar
• Soukup O, Jun D, Zdarova-Karasova J, et al. A resurrection of 7-MEOTA: a comparison with tacrine. Curr Alzheimer Res 2013;10:893–906.
   PubMed Web of Science ®Google Scholar
• Mao F, Li J, Wei H, et al. Tacrine-propargylamine derivatives with improved acetylcholinesterase inhibitory activity and lower hepatotoxicity as a potential lead compound for the treatment of Alzheimer’s disease. J Enzyme Inhib Med Chem 2015;30:995–1001. https://doi.org/10.3109/14756366.2014.1003212.
   PubMed Web of Science ®Google Scholar
• Tang J, Li J, Zhang L, et al. The divergent transformations of aromatic o-aminonitrile with carbonyl compound. J Heterocyclic Chem 2012;49:533–42. https://doi.org/10.1002/jhet.804.
   Web of Science ®Google Scholar
• Del Giudice MR, Borioni A, Mustazza C, et al. Synthesis and cholinesterase inhibitory activity of 6-, 7-methoxy-(and hydroxy-) tacrine derivatives. Farmaco 1996;51:693–8.
   PubMedGoogle Scholar
• Szymanski P, Karpiński A, Mikiciuk-Olasik E. Synthesis, biological activity and HPLC validation of 1,2,3,4-tetrahydroacridine derivatives as acetylcholinesterase inhibitors. Eur J Med Chem 2011;46:3250–7. https://doi.org/10.1016/j.ejmech.2011.04.038.
   PubMed Web of Science ®Google Scholar
• Spilovska K, Korabecny J, Kral J, et al. 7-Methoxytacrine-adamantylamine heterodimers as cholinesterase inhibitors in Alzheimer’s disease treatment–synthesis, biological evaluation and molecular modeling studies. Molecules 2013;18:2397–418. https://doi.org/10.3390/molecules18022397.
   PubMed Web of Science ®Google Scholar
• Spilovska K, Korabecny J, Sepsova V, et al. Novel tacrine-scutellarin hybrids as multipotent anti-alzheimer’s agents: design, synthesis and biological evaluation. Molecules 2017;22:1006. https://doi.org/10.3390/molecules22061006.
   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. https://doi.org/10.1016/0006-2952(61)90145-9.
   PubMed Web of Science ®Google Scholar
• Lockridge O. Review of human butyrylcholinesterase structure, function, genetic variants, history of use in the clinic, and potential therapeutic uses. Pharmacol Ther 2015;148:34–46. https://doi.org/10.1016/j.pharmthera.2014.11.011.
   PubMed Web of Science ®Google Scholar
• Greig NH, Lahiri DK, Sambamurti K. Butyrylcholinesterase: an important new target in Alzheimer’s disease therapy. Int Psychogeriatr 2002;14:77–91. https://doi.org/10.1017/s1041610203008676.
   PubMed Web of Science ®Google Scholar
• Nordberg A, Ballard C, Bullock R, et al. A review of butyrylcholinesterase as a therapeutic target in the treatment of Alzheimer’s disease. Prim Care Companion CNS Disord 2013;15:PCC.12r01412. https://doi.org/10.4088/PCC.12r01412.
   PubMedGoogle Scholar
• Inestrosa NC, Alvarez A, Pérez CA, et al. Acetylcholinesterase accelerates assembly of amyloid-beta-peptides into Alzheimer’s fibrils: possible role of the peripheral site of the enzyme. Neuron 1996;16:881–91. https://doi.org/10.1016/s0896-6273(00)80108-7.
   PubMed Web of Science ®Google Scholar
• Barak D, Ordentlich A, Kaplan D, et al. Lessons from functional analysis of AChE covalent and noncovalent inhibitors for design of AD therapeutic agents. Chem Biol Interact 2005;157–158:219–26. https://doi.org/10.1016/j.cbi.2005.10.030.
   PubMed Web of Science ®Google Scholar
• Zhang C, Lv Y, Bai R, Xie Y. Structural exploration of multifunctional monoamine oxidase B inhibitors as potential drug candidates against Alzheimer’s disease. Bioorg Chem 2021;114:105070. https://doi.org/10.1016/j.bioorg.2021.105070.
   PubMed Web of Science ®Google Scholar
• Verma P, Truhlar DG. Status and challenges of density functional theory. Trends Chem 2020;2:302–18. https://doi.org/10.1016/j.trechm.2020.02.005.
   Google Scholar
• Borštnar R, Repič M, Kržan M, et al. Irreversible inhibition of monoamine oxidase B by the antiparkinsonian medicines rasagiline and selegiline: a computational study. Eur J Organic Chem 2011;2011:6419–33. https://doi.org/10.1002/ejoc.201100873.
   Web of Science ®Google Scholar
• Di L, Kerns EH, Fan K, et al. High throughput artificial membrane permeability assay for blood-brain barrier. Eur J Med Chem 2003;38:223–32.
   PubMed Web of Science ®Google Scholar
• Wang Q, Rager JD, Weinstein K, et al. Evaluation of the MDR-MDCK cell line as a permeability screen for the blood-brain barrier. Int J Pharm 2005;288:349–59. https://doi.org/10.1016/j.ijpharm.2004.10.007.
   PubMed Web of Science ®Google Scholar
• Parepally JMR, Mandula H, Smith QR. Brain uptake of nonsteroidal anti-inflammatory drugs: ibuprofen, flurbiprofen, and indomethacin. Pharm Res 2006;23:873–81. https://doi.org/10.1007/s11095-006-9905-5.
   PubMed Web of Science ®Google Scholar
• Romero A, Cacabelos R, Oset-Gasque MJ, et al. Novel tacrine-related drugs as potential candidates for the treatment of Alzheimer’s disease. Bioorg Med Chem Lett 2013;23:1916–22. https://doi.org/10.1016/j.bmcl.2013.02.017.
   PubMed Web of Science ®Google Scholar
• Gracon SI, Knapp MJ, Berghoff WG, et al. Safety of tacrine: clinical trials, treatment IND, and postmarketing experience. Alzheimer Dis Assoc Disord 1998;12:93–101. https://doi.org/10.1097/00002093-199806000-00007.
   PubMed Web of Science ®Google Scholar
• Watkins PB, Zimmerman HJ, Knapp MJ, et al. Hepatotoxic effects of tacrine administration in patients with Alzheimer’s disease. JAMA 1994;271:992–8.
   PubMed Web of Science ®Google Scholar
• Nepovimova E, Korabecny J, Dolezal R, et al. Tacrine-trolox hybrids: a novel class of centrally active, nonhepatotoxic multi-target-directed ligands exerting anticholinesterase and antioxidant activities with low in vivo toxicity. J Med Chem 2015;58:8985–9003. https://doi.org/10.1021/acs.jmedchem.5b01325.
   PubMed Web of Science ®Google Scholar
• Lineweaver H, Burk D. The determination of enzyme dissociation constants. J Am Chem Soc 1934;56:658–66. https://doi.org/10.1021/ja01318a036 (last accessed 9 Mar 2022].
   Web of Science ®Google Scholar
• Carpenter TS, Kirshner DA, Lau EY, et al. A method to predict blood-brain barrier permeability of drug-like compounds using molecular dynamics simulations. Biophys J 2014;107:630–41. https://doi.org/10.1016/j.bpj.2014.06.024.
   PubMed Web of Science ®Google Scholar
• Muckova L, Pejchal J, Jost P, et al. Cytotoxicity of acetylcholinesterase reactivators evaluated in vitro and its relation to their structure. Drug Chem Toxicol 2019;42:252–6. https://doi.org/10.1080/01480545.2018.1432641.
   PubMed Web of Science ®Google Scholar