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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Review Article

Acridine: A Scaffold for the Development of Drugs for Alzheimer's Disease

Author(s): Anuradha Sharma* and Poonam Piplani

Volume 23, Issue 13, 2023

Published on: 01 March, 2023

Page: [1260 - 1276] Pages: 17

DOI: 10.2174/1568026623666230203141543

Price: $65

Abstract

Alzheimer's disease (AD) is drawing scientists' consideration, being one of the gravest diseases mankind will have to battle against in the near future. The number of people with AD is expected to triple in the next 40 years. It is a most common age-related multifactorial neurodegenerative disease and characterized by two histopathological hallmarks; the formation of senile plaques composed of the amyloid-β (Aβ) peptide and neurofibrillary tangles composed of hyperphosphorylated tau protein. Discovery and development of rationally designed multi-targeted ligands for the management of AD could be more beneficial than classical single targeted molecules. Acridine, a heterocyclic nucleus is a sole moiety in various existing drug molecules such as quinacrine (antimalarial), acriflavine and proflavine (antiseptics), ethacridine (abortifacient), amsacrine and nitracine (anticancer) and tacrine (anti-Alzheimer). It is proposed that acridine may combat the AD by acting on several targets like acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), dual specificity tyrosine kinase 1A (Dyrk 1A), amyloid and prion protein (PrPC) etc. involved in its pathogenesis. The main aim of this compilation is to review the most promising therapeutic developments within the vast research area dealing with acridine derivatives. Further research is required to evaluate the effectiveness of the acridine derivatives with various substitutions in the treatment of AD. In conclusion, our review will suggest the potentiality of the versatile acridine framework for drug designing and developing novel multi-target inhibitors for the Alzheimer’s disease.

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[1]
New report reveals the true impact of neurological conditions. Available from: http://www.neural.org.uk/updates/235-New-report-reveals-the-true-impact-of-neurological-conditions (Accessed on: 13 May 2022)
[2]
Brookmeyer, R.; Abdalla, N.; Kawas, C.H.; Corrada, M.M. Forecasting the prevalence of preclinical and clinical Alzheimer’s disease in the United States. Alzheimers Dement., 2018, 14(2), 121-129.
[http://dx.doi.org/10.1016/j.jalz.2017.10.009] [PMID: 29233480]
[3]
Alzheimer’s Association 2019 Alzheimer’s disease facts and figures. Alzheimers Dement., 2019, 15(3), 321-387.
[http://dx.doi.org/10.1016/j.jalz.2019.01.010]
[4]
Winner, P.P. “Alzheimer’s and Cancer: Partners in Mystery.” Alzheimer’s Disease Decoded: The History, Present, and Future of Alzheimer’s Disease and Dementia; WSPC; , 2021, p. 293. Available from: https://www.worldscientific.com/doi/abs/10.1142/9789811235115_0014
[5]
Cui, M. Past and recent progress of molecular imaging probes for β-amyloid plaques in the brain. Curr. Med. Chem., 2013, 21(1), 82-112.
[http://dx.doi.org/10.2174/09298673113209990216] [PMID: 23992340]
[6]
Srivastava, S.; Ahmad, R.; Khare, S.K. Alzheimer’s disease and its treatment by different approaches: A review. Eur. J. Med. Chem., 2021, 216, 113320.
[http://dx.doi.org/10.1016/j.ejmech.2021.113320] [PMID: 33652356]
[7]
Vecchio, I.; Sorrentino, L.; Paoletti, A.; Marra, R.; Arbitrio, M. The state of the art on acetylcholinesterase inhibitors in the treatment of Alzheimer’s disease. J. Cent. Nerv. Syst. Dis., 2021, 13, 11795735211029113.
[http://dx.doi.org/10.1177/11795735211029113] [PMID: 34285627]
[8]
Cloete, S.J.; Petzer, A.; Petzer, J.P. Interactions of dye compounds that are structurally related to methylene blue with acetylcholinesterase and butyrylcholinesterase. Chem. Biol. Drug Des., 2021, 97(4), 854-864.
[http://dx.doi.org/10.1111/cbdd.13814]
[9]
Jin, L.; Liu, C.; Zhang, N.; Zhang, R.; Yan, M.; Bhunia, A.; Zhang, Q.; Liu, M.; Han, J.; Siebert, H.C. Attenuation of human lysozyme amyloid fibrillation by ACE inhibitor captopril: A combined spectroscopy, microscopy, cytotoxicity, and docking study. Biomacromolecules, 2021, 22(5), 1910-1920.
[http://dx.doi.org/10.1021/acs.biomac.0c01802] [PMID: 33844512]
[10]
Wei, T.; Wang, J.; Liang, R.; Chen, W.; Chen, Y.; Ma, M.; He, A.; Du, Y.; Zhou, W.; Zhang, Z.; Zeng, X.; Wang, C.; Lu, J.; Guo, X.; Chen, X.W.; Wang, Y.; Tian, R.; Xiao, J.; Lei, X. Selective inhibition reveals the regulatory function of DYRK2 in protein synthesis and calcium entry. eLife, 2022, 11, e77696.
[http://dx.doi.org/10.7554/eLife.77696] [PMID: 35439114]
[11]
Zattoni, Marco Legname, Giuseppe Tackling prion diseases: A review of the patent landscape. Expert Opin. Thera. Patents, 2021, 31(12), 1097-1115.
[http://dx.doi.org/10.1080/13543776.2021.1945033]
[12]
Martorana, A.; Esposito, Z.; Koch, G. Beyond the cholinergic hypothesis: Do current drugs work in Alzheimer’s disease? CNS Neurosci. Ther., 2010, 16(4) no.
[http://dx.doi.org/10.1111/j.1755-5949.2010.00175.x] [PMID: 20560995]
[13]
Craig, L.A.; Hong, N.S.; McDonald, R.J. Revisiting the cholinergic hypothesis in the development of Alzheimer’s disease. Neurosci. Biobehav. Rev., 2011, 35(6), 1397-1409.
[http://dx.doi.org/10.1016/j.neubiorev.2011.03.001] [PMID: 21392524]
[14]
Karran, E.; Mercken, M.; Strooper, B.D. The amyloid cascade hypothesis for Alzheimer’s disease: An appraisal for the development of therapeutics. Nat. Rev. Drug Discov., 2011, 10(9), 698-712.
[http://dx.doi.org/10.1038/nrd3505] [PMID: 21852788]
[15]
Karran, E.; De Strooper, B. The amyloid hypothesis in Alzheimer disease: New insights from new therapeutics. Nat. Rev. Drug Discov., 2022, 21(4), 306-318.
[http://dx.doi.org/10.1038/s41573-022-00391-w] [PMID: 35177833]
[16]
Maccioni, R.B.; Farías, G.; Morales, I.; Navarrete, L. The revitalized tau hypothesis on Alzheimer’s disease. Arch. Med. Res., 2010, 41(3), 226-231.
[http://dx.doi.org/10.1016/j.arcmed.2010.03.007] [PMID: 20682182]
[17]
Arnsten, A.F.T.; Datta, D.; Del Tredici, K.; Braak, H. Hypothesis: Tau pathology is an initiating factor in sporadic Alzheimer’s disease. Alzheimers Dement., 2021, 17(1), 115-124.
[http://dx.doi.org/10.1002/alz.12192] [PMID: 33075193]
[18]
Laguna, A.; Aranda, S.; Barallobre, M.J.; Barhoum, R.; Fernández, E.; Fotaki, V.; Delabar, J.M.; de la Luna, S.; de la Villa, P.; Arbonés, M.L. The protein kinase DYRK1A regulates caspase-9-mediated apoptosis during retina development. Dev. Cell, 2008, 15(6), 841-853.
[http://dx.doi.org/10.1016/j.devcel.2008.10.014] [PMID: 19081073]
[19]
Tejedor, F.; Zhu, X.R.; Kaltenbach, E.; Ackermann, A.; Baumann, A.; Canal, I.; Heisenberg, M.; Fischbach, K.F.; Pongs, O. minibrain: A new protein kinase family involved in postembryonic neurogenesis in drosophila. Neuron, 1995, 14(2), 287-301.
[http://dx.doi.org/10.1016/0896-6273(95)90286-4] [PMID: 7857639]
[20]
Park, J.; Song, W.J.; Chung, K.C. Function and regulation of Dyrk1A: Towards understanding Down syndrome. Cell. Mol. Life Sci., 2009, 66(20), 3235-3240.
[http://dx.doi.org/10.1007/s00018-009-0123-2] [PMID: 19685005]
[21]
Ferrer, I.; Barrachina, M.; Puig, B.; Martínez de Lagrán, M.; Martí, E.; Avila, J.; Dierssen, M. Constitutive Dyrk1A is abnormally expressed in Alzheimer disease, Down syndrome, Pick disease, and related transgenic models. Neurobiol. Dis., 2005, 20(2), 392-400.
[http://dx.doi.org/10.1016/j.nbd.2005.03.020] [PMID: 16242644]
[22]
Wegiel, J.; Gong, C.X.; Hwang, Y.W. The role of DYRK1A in neurodegenerative diseases. FEBS J., 2011, 278(2), 236-245.
[http://dx.doi.org/10.1111/j.1742-4658.2010.07955.x] [PMID: 21156028]
[23]
Smith, B.; Medda, F.; Gokhale, V.; Dunckley, T.; Hulme, C. Recent advances in the design, synthesis, and biological evaluation of selective DYRK1A inhibitors: A new avenue for a disease modifying treatment of Alzheimer’s? ACS Chem. Neurosci., 2012, 3(11), 857-872.
[http://dx.doi.org/10.1021/cn300094k] [PMID: 23173067]
[24]
Himpel, S.; Panzer, P.; Eirmbter, K.; Czajkowska, H.; Sayed, M.; Packman, L.C.; Blundell, T.; Kentrup, H.; Grötzinger, J.; Joost, H.G.; Becker, W. Identification of the autophosphorylation sites and characterization of their effects in the protein kinase DYRK1A. Biochem. J., 2001, 359(3), 497-505.
[http://dx.doi.org/10.1042/bj3590497] [PMID: 11672423]
[25]
Kentrup, H.; Becker, W.; Heukelbach, J.; Wilmes, A.; Schürmann, A.; Huppertz, C.; Kainulainen, H.; Joost, H.G. Dyrk, a dual specificity protein kinase with unique structural features whose activity is dependent on tyrosine residues between subdomains VII and VIII. J. Biol. Chem., 1996, 271(7), 3488-3495.
[http://dx.doi.org/10.1074/jbc.271.7.3488] [PMID: 8631952]
[26]
Arriagada, P.V.; Growdon, J.H.; Hedley-Whyte, E.T.; Hyman, B.T. Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer’s disease. Neurology, 1992, 42(3), 631-639.
[http://dx.doi.org/10.1212/WNL.42.3.631] [PMID: 1549228]
[27]
Dierssen, M.; de Lagrán, M.M. DYRK1A (dual-specificity tyrosine-phosphorylated and -regulated kinase 1A): A gene with dosage effect during development and neurogenesis. Sci. World J., 2006, 6, 1911-1922.
[http://dx.doi.org/10.1100/tsw.2006.319] [PMID: 17205196]
[28]
Qian, W.; Jin, N.; Shi, J.; Yin, X.; Jin, X.; Wang, S.; Cao, M.; Iqbal, K.; Gong, C.X.; Liu, F. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (Dyrk1A) enhances tau expression. J. Alzheimers Dis., 2013, 37(3), 529-538.
[http://dx.doi.org/10.3233/JAD-130824] [PMID: 23948904]
[29]
Liu, T.; Wang, Y.; Wang, J.; Ren, C.; Chen, H.; Zhang, J. DYRK1A inhibitors for disease therapy: Current status and perspectives. Eur. J. Med. Chem., 2022, 229, 114062.
[http://dx.doi.org/10.1016/j.ejmech.2021.114062] [PMID: 34954592]
[30]
Colby, D.W.; Prusiner, S.B. Prions. Cold Spring Harb. Perspect. Biol., 2011, 3(1), a006833.
[http://dx.doi.org/10.1101/cshperspect.a006833] [PMID: 21421910]
[31]
Venko, K.; Župerl, Š.; Novič, M. Prediction of antiprion activity of therapeutic agents with structure-activity models. Mol. Divers., 2014, 18(1), 133-148.
[http://dx.doi.org/10.1007/s11030-013-9477-3] [PMID: 24052197]
[32]
Crestini, A.; Santilli, F.; Martellucci, S.; Carbone, E.; Sorice, M.; Piscopo, P.; Mattei, V. Prions and neurodegenerative diseases: A focus on Alzheimer’s disease. J. Alzheimers Dis., 2022, 85(2), 503-518.
[http://dx.doi.org/10.3233/JAD-215171] [PMID: 34864675]
[33]
Katherine, A.B. Kellett; Nigel, M. Hooper. Prion protein and Alzheimer disease. Prion, 2009, 3(4), 190-194.
[34]
Silman, I.; Sussman, J.L. Acetylcholinesterase: How is structure related to function? Chem. Biol. Interact., 2008, 175(1-3), 3-10.
[http://dx.doi.org/10.1016/j.cbi.2008.05.035] [PMID: 18586019]
[35]
Nascimento, L.A.; Nascimento, É.C.M.; Martins, J.B.L. In silico study of tacrine and acetylcholine binding profile with human acetylcholinesterase: Docking and electronic structure. J. Mol. Model., 2022, 28(9), 252.
[http://dx.doi.org/10.1007/s00894-022-05252-2] [PMID: 35947248]
[36]
Inestrosa, N.C.; Dinamarca, M.C.; Alvarez, A. Amyloid-cholinesterase interactions. FEBS J., 2008, 275(4), 625-632.
[http://dx.doi.org/10.1111/j.1742-4658.2007.06238.x] [PMID: 18205831]
[37]
Bolognesi, M.L.; Bartolini, M.; Mancini, F.; Chiriano, G.; Ceccarini, L.; Rosini, M.; Milelli, A.; Tumiatti, V.; Andrisano, V.; Melchiorre, C. Bis(7)-tacrine derivatives as multitarget-directed ligands: Focus on anticholinesterase and antiamyloid activities. ChemMedChem, 2010, 5(8), 1215-1220.
[http://dx.doi.org/10.1002/cmdc.201000086] [PMID: 20486153]
[38]
Elsinghorst, P.W.; Härtig, W.; Goldhammer, S.; Grosche, J.; Gütschow, M. A gorge-spanning, high-affinity cholinesterase inhibitor to explore β-amyloid plaques. Org. Biomol. Chem., 2009, 7(19), 3940-3946.
[http://dx.doi.org/10.1039/b909612d] [PMID: 19763296]
[39]
Colletier, J.P.; Fournier, D.; Greenblatt, H.M.; Stojan, J.; Sussman, J.L.; Zaccai, G.; Silman, I.; Weik, M. Structural insights into substrate traffic and inhibition in acetylcholinesterase. EMBO J., 2006, 25(12), 2746-2756.
[http://dx.doi.org/10.1038/sj.emboj.7601175] [PMID: 16763558]
[40]
Dileep, K.V.; Ihara, K.; Mishima-Tsumagari, C.; Kukimoto-Niino, M.; Yonemochi, M.; Hanada, K.; Shirouzu, M.; Zhang, K.Y.J. Crystal structure of human acetylcholinesterase in complex with tacrine: Implications for drug discovery. Int. J. Biol. Macromol., 2022, 210, 172-181.
[http://dx.doi.org/10.1016/j.ijbiomac.2022.05.009] [PMID: 35526766]
[41]
Kumawat, A.; Raheem, S.; Ali, F.; Dar, T.A.; Chakrabarty, S.; Rizvi, M.A. Organoselenium compounds as acetylcholinesterase inhibitors: Evidence and mechanism of mixed inhibition. J. Phys. Chem. B, 2021, 125(6), 1531-1541.
[http://dx.doi.org/10.1021/acs.jpcb.0c08111] [PMID: 33538163]
[42]
Mukhametgalieva, A.R.; Lushchekina, S.V.; Aglyamova, A.R.; Masson, P. Steady-state kinetic analysis of human cholinesterases over wide concentration ranges of competing substrates. Biochim. Biophys. Acta. Proteins Proteomics, 2022, 1870(1), 140733.
[http://dx.doi.org/10.1016/j.bbapap.2021.140733] [PMID: 34662731]
[43]
Chiou, S.Y.; Weng, T.T.; Lin, G.Z.; Lu, R.J.; Jian, S.Y.; Lin, G. Molecular docking of different inhibitors and activators to butyrylcholinesterase. J. Biomol. Struct. Dyn., 2015, 33(3), 563-572.
[http://dx.doi.org/10.1080/07391102.2014.896749] [PMID: 24625272]
[44]
Nguyen, P.; Derreumaux, P. Understanding amyloid fibril nucleation and Aβ oligomer/drug interactions from computer simulations. Acc. Chem. Res., 2014, 47(2), 603-611.
[45]
Kumari, A.; Shrivastava, N.; Mishra, M.; Somvanshi, P.; Grover, A. Inhibitory mechanism of an antifungal drug, caspofungin against amyloid β peptide aggregation: Repurposing via neuroinformatics and an experimental approach. Mol. Cell. Neurosci., 2021, 112, 103612.
[http://dx.doi.org/10.1016/j.mcn.2021.103612] [PMID: 33722677]
[46]
Paul, R.; Bera, S.; Devi, M.; Paul, S. Inhibition of Aβ 16–22 peptide aggregation by small molecules and their permeation through POPC lipid bilayer: Insight from molecular dynamics simulation study. J. Chem. Inf. Model., 2022, 62(21), 5193-5207.
[http://dx.doi.org/10.1021/acs.jcim.1c01366] [PMID: 35306811]
[47]
Soundararajan, M.; Roos, A.K.; Savitsky, P.; Filippakopoulos, P.; Kettenbach, A.N.; Olsen, J.V.; Gerber, S.A.; Eswaran, J.; Knapp, S.; Elkins, J.M. Structures of Down syndrome kinases, DYRKs, reveal mechanisms of kinase activation and substrate recognition. Structure, 2013, 21(6), 986-996.
[http://dx.doi.org/10.1016/j.str.2013.03.012] [PMID: 23665168]
[48]
Riesner, D. Biochemistry and structure of PrPC and PrPSc. Br. Med. Bull., 2003, 66(1), 21-33.
[http://dx.doi.org/10.1093/bmb/66.1.21] [PMID: 14522846]
[49]
Mirali, M.; Jafariazar, Z.; Mirzaei, M. Loading tacrine alzheimer’s drug at the carbon nanotube: DFT approach. Lab in Silico, 2021, 2(1), 3-8.
[50]
Sahiba, N.; Sethiya, A.; Soni, J.; Agarwal, S. Acridine‐1,8‐diones: Synthesis and biological applications. ChemistrySelect, 2021, 6(9), 2210-2251.
[http://dx.doi.org/10.1002/slct.202004536]
[51]
Sondhi, S.M.; Dinodia, M.; Jain, S.; Kumar, A. Synthesis of biologically active N-methyl derivatives of amidines and cyclized five-membered products of amidines with oxalyl chloride. Eur. J. Med. Chem., 2008, 43(12), 2824-2830.
[http://dx.doi.org/10.1016/j.ejmech.2007.10.005] [PMID: 18022734]
[52]
Sondhi, S.M.; Rani, R.; Roy, P.; Agrawal, S.K.; Saxena, A.K. Microwave-assisted synthesis of N-substituted cyclic imides and their evaluation for anticancer and anti-inflammatory activities. Bioorg. Med. Chem. Lett., 2009, 19(5), 1534-1538.
[http://dx.doi.org/10.1016/j.bmcl.2008.07.048] [PMID: 19201604]
[53]
Prasher, P.; Sharma, M. Medicinal chemistry of acridine and its analogues. MedChemComm, 2018, 9(10), 1589-1618.
[http://dx.doi.org/10.1039/C8MD00384J] [PMID: 30429967]
[54]
Sondhi, S.M.; Singh, J.; Rani, R.; Gupta, P.P.; Agrawal, S.K.; Saxena, A.K. Synthesis, anti-inflammatory and anticancer activity evaluation of some novel acridine derivatives. Eur. J. Med. Chem., 2010, 45(2), 555-563.
[http://dx.doi.org/10.1016/j.ejmech.2009.10.042]
[55]
Kozurkova, M.; Sabolova, D.; Kristian, P. A new look at 9‐substituted acridines with various biological activities. J. Appl. Toxicol., 2021, 41(1), 175-189.
[http://dx.doi.org/10.1002/jat.4072] [PMID: 32969520]
[56]
Gabriel, I. ‘Acridines’ as new horizons in antifungal treatment. Molecules, 2020, 25(7), 1480.
[http://dx.doi.org/10.3390/molecules25071480] [PMID: 32218216]
[57]
Silva, C.F.M.; Pinto, D.C.G.A.; Fernandes, P.A.; Silva, A.M.S. Evolution of acridines and xanthenes as a core structure for the development of antileishmanial agents. Pharmaceuticals, 2022, 15(2), 148.
[http://dx.doi.org/10.3390/ph15020148] [PMID: 35215261]
[58]
Albino, S.L.; da Silva, J.M.; de C Nobre, M.S.; de M E Silva, Y.M.S.; Santos, M.B.; de Araújo, R.S.A.; do C A de Lima, M.; Schmitt, M.; de Moura, R.O. Bioprospecting of nitrogenous heterocyclic scaffolds with potential action for neglected parasitosis: A review. Curr. Pharm. Des., 2020, 26(33), 4112-4150.
[http://dx.doi.org/10.2174/1381612826666200701160904] [PMID: 32611290]
[59]
Gündüz, M.G.; Tahir, M.N.; Armaković, S.; Özkul Koçak, C.; Armaković, S.J. Design, synthesis and computational analysis of novel acridine-(sulfadiazine/sulfathiazole) hybrids as antibacterial agents. J. Mol. Struct., 2019, 1186, 39-49.
[http://dx.doi.org/10.1016/j.molstruc.2019.03.010]
[60]
Fonte, M.; Tassi, N.; Gomes, P.; Teixeira, C. Acridine-based antimalarials-from the very first synthetic antimalarial to recent developments. Molecules, 2021, 26(3), 600.
[http://dx.doi.org/10.3390/molecules26030600] [PMID: 33498868]
[61]
Keri, R.S.; Quintanova, C.; Marques, S.M.; Esteves, A.R.; Cardoso, S.M.; Santos, M.A. Design, synthesis and neuroprotective evaluation of novel tacrine–benzothiazole hybrids as multi-targeted compounds against Alzheimer’s disease. Bioorg. Med. Chem., 2013, 21(15), 4559-4569.
[http://dx.doi.org/10.1016/j.bmc.2013.05.028] [PMID: 23768661]
[62]
Li, S.Y.; Wang, X.B.; Xie, S.S.; Jiang, N.; Wang, K.D.G.; Yao, H.Q.; Sun, H.B.; Kong, L.Y. Multifunctional tacrine–flavonoid hybrids with cholinergic, β-amyloid-reducing, and metal chelating properties for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2013, 69, 632-646.
[http://dx.doi.org/10.1016/j.ejmech.2013.09.024] [PMID: 24095756]
[63]
El-Malah, A.; Gedawy, E.M.; Kassab, A.E.; Salam, R.M.A. Novel tacrine analogs as potential cholinesterase inhibitors in Alzheimer’s disease. Arch. Pharm., 2014, 347(2), 96-103.
[http://dx.doi.org/10.1002/ardp.201300121]
[64]
Thiratmatrakul, Supatra; Yenjai, Chavi; Waiwut, Pornthip; Vajragupta, Opa; Reubroycharoen, Prasert; Tohda, Michihisa; Boonyarat, Chantana Synthesis biological evaluation and molecular modeling study of novel tacrine–carbazole hybrids as potential multifunctional agents for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2014, 75, 21-30.
[http://dx.doi.org/10.1016/j.ejmech.2014.01.020] [PMID: 24508831]
[65]
Li, Q.; Chen, Y.; Xing, S.; Liao, Q.; Xiong, B.; Wang, Y.; Lu, W.; He, S.; Feng, F.; Liu, W.; Chen, Y.; Sun, H. Highly potent and selective butyrylcholinesterase inhibitors for cognitive improvement and neuroprotection. J. Med. Chem., 2021, 64(10), 6856-6876.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00167] [PMID: 33973470]
[66]
Menghani, Y.R.; Bhattad, D.M.; Chandak, K.K.; Taksande, J.R.; Umekar, M.J.A. Review: Pharmacological and herbal remedies in The Management of Neurodegenerative disorder (Alzheimer’s). Int. J. Pharmacogn. Life Sci., 2021, 2(1), 18-27.
[http://dx.doi.org/10.33545/27072827.2021.v2.i1a.23]
[67]
Merde, İ.B.; Önel, G.T.; Türkmenoğlu, B.; Gürsoy, Ş.; Dilek, E.; Özçelik, A.B.; Uysal, M. Synthesis of (p‐ tolyl)‐3(2 H)pyridazinone derivatives as novel acetylcholinesterase inhibitors. ChemistrySelect, 2022, 7(28), e202201606.
[http://dx.doi.org/10.1002/slct.202201606]
[68]
Bargagna, B.; Ciccone, L.; Nencetti, S.; Santos, M.A.; Chaves, S.; Camodeca, C.; Orlandini, E. Multifklimer’s klgents. Molecules, 2021, 26(19), 6015.
[http://dx.doi.org/10.3390/molecules26196015] [PMID: 34641559]
[69]
Truong, B.; Quiroz, J.; Priefer, R. Acetylcholinesterase inhibitors for Alzheimer’s disease: Past, present, and potential future. Med. Res. Arch., 2020, 8(12)
[http://dx.doi.org/10.18103/mra.v8i12.2271]
[70]
Manhas, S.; Khan, Z.A.; Gupta, M. Current Status of Alzheimer’s Disease in India: Prevalence, Stigma, and Myths. Smart Healthcare Monitoring Using IoT with 5G; CRC Press, 2021, pp. 81-104.
[http://dx.doi.org/10.1201/9781003171829-5]
[71]
Makhaeva, G.F.; Lushchekina, S.V.; Kovaleva, N.V.; Yu Astakhova, T.; Boltneva, N.P.; Rudakova, E.V.; Serebryakova, O.G.; Proshin, A.N.; Serkov, I.V.; Trofimova, T.P.; Tafeenko, V.A.; Radchenko, E.V.; Palyulin, V.A.; Fisenko, V.P.; Korábečný, J.; Soukup, O.; Richardson, R.J. Amiridine-piperazine hybrids as cholinesterase inhibitors and potential multitarget agents for Alzheimer’s disease treatment. Bioorg. Chem., 2021, 112, 104974.
[http://dx.doi.org/10.1016/j.bioorg.2021.104974] [PMID: 34029971]
[72]
Disney, A.A.; Higley, M.J. Diverse spatiotemporal scales of cholinergic signaling in the neocortex. J. Neurosci., 2020, 40(4), 720-725.
[http://dx.doi.org/10.1523/JNEUROSCI.1306-19.2019] [PMID: 31969490]
[73]
Haidar, H.M.R. Evaluation of the Anti-Cholinesterase Activity and Hepatotoxicity of Selected Chemical Compounds. MS Thesis. Beirut Arab University. Faculty of Pharmacy. Department of Pharmacology Science (Pharmacognosy), 2018.
[74]
Sang, Z.; Wang, K.; Dong, J.; Tang, L. Alzheimer’s disease: Updated multi-targets therapeutics are in clinical and in progress. Eur. J. Med. Chem., 2022, 238, 114464.
[http://dx.doi.org/10.1016/j.ejmech.2022.114464] [PMID: 35635955]
[75]
Ahmed, I.B.; Kibou, Z.; Choukchou-Braham, N. Recent advances in the synthesis of tacrine derivatives as multifunctional agents for Alzheimer’s disease. Curr. Org. Chem., 2021, 25(21), 2579-2624.
[http://dx.doi.org/10.2174/1385272825666210716154531]
[76]
Donaire-Arias, A.; Montagut, A.M.; Puig de la Bellacasa, R.; Estrada-Tejedor, R.; Teixidó, J.; Borrell, J.I. 1H-Pyrazolo[3,4-b]pyridines: Synthesis and biomedical applications. Molecules, 2022, 27(7), 2237.
[http://dx.doi.org/10.3390/molecules27072237] [PMID: 35408636]
[77]
Mak, S.; Li, W.; Fu, H.; Luo, J.; Cui, W.; Hu, S.; Pang, Y.; Carlier, P.R.; Tsim, K.W.; Pi, R.; Han, Y. Promising tacrine/huperzine A‐based dimeric acetylcholinesterase inhibitors for neurodegenerative disorders: From relieving symptoms to modifying diseases through multitarget. J. Neurochem., 2021, 158(6), 1381-1393.
[http://dx.doi.org/10.1111/jnc.15379] [PMID: 33930191]
[78]
Mishra, P.; Kumar, A.; Panda, G. Anti-cholinesterase hybrids as multi-target-directed ligands against Alzheimer’s disease (1998-2018). Bioorg. Med. Chem., 2019, 27(6), 895-930.
[http://dx.doi.org/10.1016/j.bmc.2019.01.025] [PMID: 30744931]
[79]
Hamulakova, S.; Janovec, L.; Soukup, O.; Jun, D.; Janockova, J.; Hrabinova, M.; Sepsova, V.; Kuca, K. Tacrine-coumarin and tacrine-7-chloroquinoline hybrids with thiourea linkers: Cholinesterase inhibition properties, kinetic study, molecular docking and permeability assay for blood-brain barrier. Curr. Alzheimer Res., 2018, 15(12), 1096-1105.
[http://dx.doi.org/10.2174/1567205015666180711110750] [PMID: 29992880]
[80]
Nepovimova, E.; Svobodova, L.; Dolezal, R.; Hepnarova, V.; Junova, L.; Jun, D.; Korabecny, J.; Kucera, T.; Gazova, Z.; Motykova, K.; Kubackova, J.; Bednarikova, Z.; Janockova, J.; Jesus, C.; Cortes, L.; Pina, J.; Rostohar, D.; Serpa, C.; Soukup, O.; Aitken, L.; Hughes, R.E.; Musilek, K.; Muckova, L.; Jost, P.; Chvojkova, M.; Vales, K.; Valis, M.; Chrienova, Z.; Chalupova, K.; Kuca, K. Tacrine – Benzothiazoles: Novel class of potential multitarget anti-Alzheimeŕs drugs dealing with cholinergic, amyloid and mitochondrial systems. Bioorg. Chem., 2021, 107, 104596.
[http://dx.doi.org/10.1016/j.bioorg.2020.104596] [PMID: 33421953]
[81]
El-Malah, A.; Abouelatta, A.I.Y.; Mahmoud, Z.; Salem, H.H. New cyclooctathienopyridine derivatives in the aim of discovering better Anti-Alzheimer’s agents. J. Mol. Struct., 2019, 1196, 162-168.
[http://dx.doi.org/10.1016/j.molstruc.2019.06.071]
[82]
Chianella, C.; Gragnaniello, D.; Maisano Delser, P.; Visentini, M.F.; Sette, E.; Tola, M.R.; Barbujani, G.; Fuselli, S. BCHE and CYP2D6 genetic variation in Alzheimer’s disease patients treated with cholinesterase inhibitors. Eur. J. Clin. Pharmacol., 2011, 67(11), 1147-1157.
[http://dx.doi.org/10.1007/s00228-011-1064-x] [PMID: 21630031]
[83]
Islam, F.; Khadija, J.F.; Harun-Or-Rashid, M. Bioactive compounds and their derivatives: An insight into prospective phytotherapeutic approach against Alzheimer’s disease. Oxid. Med. Cell. Longev., 2022, 5100904, 1916-1922.
[84]
Islam, F.; Nafady, M.H.; Islam, M.R.; Saha, S.; Rashid, S.; Akter, A.; Or-Rashid, M.H.; Akhtar, M.F.; Perveen, A.; Md Ashraf, G.; Rahman, M.H.; Hussein Sweilam, S. Resveratrol and neuroprotection: An insight into prospective therapeutic approaches against Alzheimer’s disease from bench to bedside. Mol. Neurobiol., 2022, 59(7), 4384-4404.
[http://dx.doi.org/10.1007/s12035-022-02859-7] [PMID: 35545730]
[85]
Mao, F.; Huang, L.; Luo, Z.; Liu, A.; Lu, C.; Xie, Z.; Li, X. O-Hydroxyl- or o-amino benzylamine-tacrine hybrids: Multifunctional biometals chelators, antioxidants, and inhibitors of cholinesterase activity and amyloid-β aggregation. Bioorg. Med. Chem., 2012, 20(19), 5884-5892.
[http://dx.doi.org/10.1016/j.bmc.2012.07.045] [PMID: 22944335]
[86]
Darvesh, S.; Hopkins, D.A.; Geula, C. Neurobiology of butyrylcholinesterase. Nat. Rev. Neurosci., 2003, 4(2), 131-138.
[http://dx.doi.org/10.1038/nrn1035] [PMID: 12563284]
[87]
Greig, N.H.; Utsuki, T.; Ingram, D.K.; Wang, Y.; Pepeu, G.; Scali, C.; Yu, Q.S.; Mamczarz, J.; Holloway, H.W.; Giordano, T.; Chen, D.; Furukawa, K.; Sambamurti, K.; Brossi, A.; Lahir, D.K. Many tangles and plaques in the brain of Alzheimer’s disease patients contain BChE activity; Darvesh, Hopkins, & Geula, 2003.
[88]
Chen, Y.; Sun, J.; Peng, S.; Liao, H.; Zhang, Y.; Lehmann, J. Tacrine-flurbiprofen hybrids as multifunctional drug candidates for the treatment of Alzheimer’s disease. Arch. Pharm., 2013, 346(12), 865-871.
[http://dx.doi.org/10.1002/ardp.201300074] [PMID: 24203864]
[89]
Korabecny, J.; Dolezal, R.; Cabelova, P.; Horova, A.; Hruba, E.; Ricny, J.; Sedlacek, L.; Nepovimova, E.; Spilovska, K.; Andrs, M.; Musilek, K.; Opletalova, V.; Sepsova, V.; Ripova, D.; Kuca, K. 7-MEOTA–donepezil like compounds as cholinesterase inhibitors: Synthesis, pharmacological evaluation, molecular modeling and QSAR studies. Eur. J. Med. Chem., 2014, 82, 426-438.
[http://dx.doi.org/10.1016/j.ejmech.2014.05.066] [PMID: 24929293]
[90]
Hamulakova, S.; Imrich, J.; Janovec, L.; Kristian, P.; Danihel, I.; Holas, O.; Pohanka, M.; Böhm, S.; Kozurkova, M.; Kuca, K. Novel tacrine/acridine anticholinesterase inhibitors with piperazine and thiourea linkers. Int. J. Biol. Macromol., 2014, 70, 435-439.
[91]
Xie, S.S.; Lan, J.S.; Wang, X.B.; Jiang, N.; Dong, G.; Li, Z.R.; Wang, K.D.G.; Guo, P.P.; Kong, L.Y. Multifunctional tacrine–trolox hybrids for the treatment of Alzheimer’s disease with cholinergic, antioxidant, neuroprotective and hepatoprotective properties. Eur. J. Med. Chem., 2015, 93, 42-50.
[http://dx.doi.org/10.1016/j.ejmech.2015.01.058] [PMID: 25656088]
[92]
Xie, S.S.; Wang, X.; Jiang, N.; Yu, W.; Wang, K.D.G.; Lan, J.S.; Li, Z.R.; Kong, L.Y. Multi-target tacrine-coumarin hybrids: Cholinesterase and monoamine oxidase B inhibition properties against Alzheimer’s disease. Eur. J. Med. Chem., 2015, 95, 153-165.
[http://dx.doi.org/10.1016/j.ejmech.2015.03.040] [PMID: 25812965]
[93]
Zha, X.; Lamba, D.; Zhang, L.; Lou, Y.; Xu, C.; Kang, D.; Chen, L.; Xu, Y.; Zhang, L.; De Simone, A.; Samez, S.; Pesaresi, A.; Stojan, J.; Lopez, M.G.; Egea, J.; Andrisano, V.; Bartolini, M. Novel tacrine-benzofuran hybrids as potent multitarget-directed ligands for the treatment of Alzheimer’s disease: Design, synthesis, biological evaluation, and X-ray crystallography. J. Med. Chem., 2016, 59(1), 114-131.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01119] [PMID: 26632651]
[94]
Chiti, F.; Dobson, C.M. Protein misfolding, functional amyloid, and human disease. Annu. Rev. Biochem., 2006, 75(1), 333-366.
[http://dx.doi.org/10.1146/annurev.biochem.75.101304.123901] [PMID: 16756495]
[95]
Ono, K.; Hamaguchi, T.; Naiki, H.; Yamada, M. Anti-amyloidogenic effects of antioxidants: Implications for the prevention and therapeutics of Alzheimer’s disease. Biochim. Biophys. Acta Mol. Basis Dis., 2006, 1762(6), 575-586.
[http://dx.doi.org/10.1016/j.bbadis.2006.03.002] [PMID: 16644188]
[96]
Sengupta, C.; Mitra, P.; Chatterjee, S.; Bhattacharjee, G.; Satpati, B.; Basu, S. Photoinduced electronic interactions between acridine derivatives and small gold nanoparticles: A spectroscopic insight. J. Mol. Liq., 2018, 272, 198-208.
[http://dx.doi.org/10.1016/j.molliq.2018.09.080]
[97]
Antosova, A.; Chelli, B.; Bystrenova, E.; Siposova, K.; Valle, F.; Imrich, J.; Vilkova, M.; Kristian, P.; Biscarini, F.; Gazova, Z. Structure-activity relationship of acridine derivatives to amyloid aggregation of lysozyme. Biochim. Biophys. Acta, Gen. Subj., 2011, 1810(4), 465-474.
[http://dx.doi.org/10.1016/j.bbagen.2011.01.007] [PMID: 21276838]
[98]
Kawasaki, M.; Fuchigami, T.; Kobashi, N.; Nakagaki, T.; Sano, K.; Atarashi, R.; Yoshida, S.; Haratake, M.; Nishida, N.; Nakayama, M. Development of radioiodinated acridine derivatives for in vivo imaging of prion deposits in the brain. Bioorg. Med. Chem., 2017, 25(3), 1085-1093.
[http://dx.doi.org/10.1016/j.bmc.2016.12.020] [PMID: 28041803]
[99]
Ulicna, K.; Bednarikova, Z.; Hsu, W.T.; Holztragerova, M.; Wu, J.W.; Hamulakova, S.; Wang, S.S.S.; Gazova, Z. Lysozyme amyloid fibrillization in presence of tacrine/acridone-coumarin heterodimers. Colloids Surf. B Biointerfaces, 2018, 166, 108-118.
[http://dx.doi.org/10.1016/j.colsurfb.2018.03.010] [PMID: 29550545]
[100]
Islam, F.; Mitra, S.; Nafady, M.H.; Rahman, M.T.; Tirth, V.; Akter, A.; Emran, T.B.; Mohamed, A.A.R.; Algahtani, A.; El-Kholy, S.S. Neuropharmacological and antidiabetic potential of Lannea coromandelica (Houtt.) merr. leaves extract: An experimental analysis. Evid. Based Complement. Alternat. Med., 2022, 2022, 6144733.
[http://dx.doi.org/10.1155/2022/6144733] [PMID: 35388308]
[101]
Rastegari, A.; Safavi, M.; Vafadarnejad, F.; Najafi, Z.; Hariri, R.; Bukhari, S.N.A.; Iraji, A.; Edraki, N.; Firuzi, O.; Saeedi, M.; Mahdavi, M.; Akbarzadeh, T. Synthesis and evaluation of novel arylisoxazoles linked to tacrine moiety: In vitro and in vivo biological activities against Alzheimer’s disease. Mol. Divers., 2022, 26(1), 409-428.
[http://dx.doi.org/10.1007/s11030-021-10248-w] [PMID: 34273065]
[102]
Maciejewska, K.; Czarnecka, K.; Kręcisz, P.; Niedziałek, D.; Wieczorek, G.; Skibiński, R.; Szymański, P. Novel cyclopentaquinoline and acridine analogs as multifunctional, potent drug candidates in Alzheimer’s disease. Int. J. Mol. Sci., 2022, 23(11), 5876.
[http://dx.doi.org/10.3390/ijms23115876] [PMID: 35682556]
[103]
Deboever, E.; Fistrovich, A.; Hulme, C.; Dunckley, T. The omnipresence of DYRK1A in human diseases. Int. J. Mol. Sci., 2022, 23(16), 9355.
[http://dx.doi.org/10.3390/ijms23169355] [PMID: 36012629]
[104]
Gregory, D. Cuny; Maxime, Robin; Natalia, P. Ulyanova; Debasis, Patnaik; Valerie, Pique; Gilles, Casano; Ji-Feng, Liu; Xiangjie, Lin; Jun, Xian; Marcie, A. Glicksman; Ross, L. Stein; Jonathan, M.G. Higgins Structure–activity relationship study of acridine analogs as haspin and DYRK2 kinase inhibitors. Bioorg. Med. Chem. Lett., 2010, 20, 3491-3494.
[105]
Zeinyeh, W.; Esvan, Y.J.; Josselin, B.; Defois, M.; Baratte, B.; Knapp, S.; Chaikuad, A.; Anizon, F.; Giraud, F.; Ruchaud, S.; Moreau, P. Synthesis and biological evaluation of Haspin inhibitors: Kinase inhibitory potency and cellular activity. Eur. J. Med. Chem., 2022, 236, 114369.
[http://dx.doi.org/10.1016/j.ejmech.2022.114369] [PMID: 35447555]
[106]
Higgins, J.; Cuny, G.D.; Glicksman, M.; Patnaik, D.; Robin, M.; Stein, R.L.; Xian, J. Acridines as inhibitors of haspin and dyrk kinases. U.S. Patent 03178, 2011.
[107]
Uliassi, E.; Nikolic, L.; Bolognesi, M.L.; Legname, G. Therapeutic strategies for identifying small molecules against prion diseases. Cell Tissue Res., 2022. [Epub ahead of print].
[http://dx.doi.org/10.1007/s00441-021-03573-x] [PMID: 34989851]
[108]
Vallabh, S.M.; Minikel, E.V.; Schreiber, S.L.; Lander, E.S. Towards a treatment for genetic prion disease: Trials and biomarkers. Lancet Neurol., 2020, 19(4), 361-368.
[http://dx.doi.org/10.1016/S1474-4422(19)30403-X] [PMID: 32199098]
[109]
Aguzzi, A.; Sigurdson, C.; Heikenwaelder, M. Molecular mechanisms of prion pathogenesis. Annu. Rev. Pathol., 2008, 3(1), 11-40.
[http://dx.doi.org/10.1146/annurev.pathmechdis.3.121806.154326] [PMID: 18233951]
[110]
Krance, S.H.; Luke, R.; Shenouda, M.; Israwi, A.R.; Colpitts, S.J.; Darwish, L.; Strauss, M.; Watts, J.C. Cellular models for discovering prion disease therapeutics: Progress and challenges. J. Neurochem., 2020, 153(2), 150-172.
[http://dx.doi.org/10.1111/jnc.14956] [PMID: 31943194]
[111]
Doh-ura, K.; Iwaki, T.; Caughey, B. Lysosomotropic agents and cysteine protease inhibitors inhibit scrapie-associated prion protein accumulation. J. Virol., 2000, 74(10), 4894-4897.
[http://dx.doi.org/10.1128/jvi.74.10.4894-4897.2000] [PMID: 10775631]
[112]
Korth, C.; May, B.C.H.; Cohen, F.E.; Prusiner, S.B. Acridine and phenothiazine derivatives as pharmacotherapeutics for Prion disease. Proc. Natl. Acad. Sci., 2001, 98(17), 9836-9841.
[http://dx.doi.org/10.1073/pnas.161274798] [PMID: 11504948]
[113]
Nguyen Thi, H.T.; Lee, C.Y.; Teruya, K.; Ong, W.Y.; Doh-ura, K.; Go, M.L. Antiprion activity of functionalized 9-aminoacridines related to quinacrine. Bioorg. Med. Chem., 2008, 16(14), 6737-6746.
[http://dx.doi.org/10.1016/j.bmc.2008.05.060] [PMID: 18556207]
[114]
Nguyen, T.; Sakasegawa, Y.; Doh-ura, K.; Go, M.L. Anti-prion activities and drug-like potential of functionalized quinacrine analogs with basic phenyl residues at the 9-amino position. Eur. J. Med. Chem., 2011, 46(7), 2917-2929.
[http://dx.doi.org/10.1016/j.ejmech.2011.04.016] [PMID: 21531054]
[115]
Villa, V.; Tonelli, M.; Thellung, S.; Corsaro, A.; Tasso, B.; Novelli, F.; Canu, C.; Pino, A.; Chiovitti, K.; Paludi, D.; Russo, C.; Sparatore, A.; Aceto, A.; Boido, V.; Sparatore, F.; Florio, T. Efficacy of novel acridine derivatives in the inhibition of hPrP90-231 prion protein fragment toxicity. Neurotox. Res., 2011, 19(4), 556-574.
[http://dx.doi.org/10.1007/s12640-010-9189-8] [PMID: 20405353]

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