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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Review Article

Progress and Development of Carbazole Scaffold Based as Potential Anti- Alzheimer Agents Using MTDL Approach

Author(s): Nitin Kumar*, Pankaj Gupta and Sahil Bansal

Volume 19, Issue 12, 2022

Published on: 20 May, 2022

Page: [1049 - 1067] Pages: 19

DOI: 10.2174/1570180819666220314144219

Price: $65

Abstract

Alzheimer’s is a neurodegenerative disease (NDs) found in old age people with associated most common symptom dementia. MTDLs (Multi-Target Direct Ligand strategy) is based on a combination of two or more bioactive pharmacophores into a single molecule and this phenomenon has received a great attention in the new era of modern drug discovery and emerging as a choice to treat this complex Alzheimer’s disease (AD). In last fifteen years, many research groups designed, and synthesized new carbazole integrated molecules linked with other bioactive pharmacophores like thiazoles, carvedilol, α- naphthylaminopropan-2-ol, tacrine, ferulic acid, piperazine, coumarin, chalcones, stilbene, benzyl piperidine, adamantane, quinoline, phthalocyanines, α-amino phosphonate, thiosemicarbazones, hydrazones, etc. derivatives using MTDLs approach to confront AD. The present review entails the scientific data on carbazole hybrids as potential Anti-Alzheimer activities from 2007 to 2021 that have shown potential anti-Alzheimer activities through multiple target pathways thereby promising hope for new drug development to confront AD.

Keywords: Alzheimer’s disease (AD), carbazole, Multi-target-drug-ligand strategy (MTDLs), acetylcholinesterase (AChE), butyl cholinesterase (BChE), BACE 1 (beta secretase choline esterase enzyme), SAR (structure activity relationship), search engines: google scholar, PubMed.gov.

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[1]
Song, M.Q.; Min, W.; Wang, J.; Si, X.X.; Wang, X.J.; Liu, Y.W.; Shi, D.H. Design, synthesis and biological evaluation of new carbazole-coumarin hybrids as dual binding site inhibitors of acetylcholinesterase. J. Mol. Struct., 2021, 1229, 129784.
[http://dx.doi.org/10.1016/j.molstruc.2020.129784]
[2]
Zhang, X.; Wang, Y.; Wang, S.N.; Chen, Q.H.; Tu, Y.L.; Yang, X.H.; Chen, J.K.; Yan, J.W.; Pi, R.B.; Wang, Y. Discovery of a novel multi-functional carbazole–aminoquinoline dimer for Alzheimer’s disease: Copper selective chelation, anti-amyloid aggregation, and neuropro-tection. Med. Chem. Res., 2018, 27(3), 777-784.
[http://dx.doi.org/10.1007/s00044-017-2101-9]
[3]
Martin, J.B. Molecular basis of the neurodegenerative disorders. N. Engl. J. Med., 1999, 340(25), 1970-1980.
[http://dx.doi.org/10.1056/NEJM199906243402507] [PMID: 10379022]
[4]
Prince, M.; Comas-Herrera, A.; Knapp, M.; Guerchet, M.; Karagiannidou, M. World Alzheimer report 2016: Improving healthcare for people living with dementia: Coverage, quality and costs now and in the future. In: Alzheimer’s Disease International; ADI: London, UK, 2016.
[5]
Ballard, C.; Gauthier, S.; Corbett, A.; Brayne, C.; Aarsland, D.; Jones, E. Alzheimer’s disease. Lancet, 2011, 377(9770), 1019-1031.
[http://dx.doi.org/10.1016/S0140-6736(10)61349-9] [PMID: 21371747]
[6]
Gaugler, J.; James, B.; Johnson, T.; Marin, A.; Weuve, J. 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]
[7]
Selkoe, D.J.; Yamazaki, T.; Citron, M.; Podlisny, M.B.; Koo, E.H.; Teplow, D.B.; Haass, C. The role of APP processing and trafficking pathways in the formation of amyloid β-protein. Ann. N. Y. Acad. Sci., 1996, 777(1), 57-64.
[http://dx.doi.org/10.1111/j.1749-6632.1996.tb34401.x] [PMID: 8624127]
[8]
Mishra, C.B.; Gusain, S.; Shalini, S.; Kumari, S.; Prakash, A.; Kumari, N.; Yadav, A.K.; Kumari, J.; Kumar, K.; Tiwari, M. Development of novel carbazole derivatives with effective multifunctional action against Alzheimer’s diseases: Design, synthesis, in silico, in vitro and in vivo investigation. Bioorg. Chem., 2020, 95, 103524.
[http://dx.doi.org/10.1016/j.bioorg.2019.103524] [PMID: 31918396]
[9]
Francis, P.T.; Palmer, A.M.; Snape, M.; Wilcock, G.K. The cholinergic hypothesis of Alzheimer’s disease: A review of progress. J. Neurol. Neurosurg. Psychiatry, 1999, 66(2), 137-147.
[http://dx.doi.org/10.1136/jnnp.66.2.137] [PMID: 10071091]
[10]
Patterson, C. The state of the art of dementia research: New frontiers. World Alzheimer Report 2018. Available from https://www.alzint.org/u/WorldAlzheimerReport2018.pdf
[11]
Sadeghian, B.; Sakhteman, A.; Faghih, Z.; Nadri, H.; Edraki, N.; Iraji, A.; Sadeghian, I.; Rezaei, Z. Design, synthesis and biological activity evaluation of novel carbazole-benzylpiperidine hybrids as potential anti Alzheimer agents. J. Mol. Struct., 2020, 1221, 128793.
[http://dx.doi.org/10.1016/j.molstruc.2020.128793]
[12]
McDade, E.; Bateman, R.J. Stop Alzheimer’s before it starts. Nature, 2017, 547(7662), 153-155.
[http://dx.doi.org/10.1038/547153a] [PMID: 28703214]
[13]
Makhaeva, G.F.; Shevtsova, E.F.; Boltneva, N.P.; Lushchekina, S.V.; Kovaleva, N.V.; Rudakova, E.V.; Bachurin, S.O.; Richardson, R.J. Overview of novel multifunctional agents based on conjugates of γ-carbolines, carbazoles, tetrahydrocarbazoles, phenothiazines, and ami-noadamantanes for treatment of Alzheimer’s disease. Chem. Biol. Interact., 2019, 308, 224-234.
[http://dx.doi.org/10.1016/j.cbi.2019.05.020] [PMID: 31100279]
[14]
Rampa, A.; Bartolini, M.; Bisi, A.; Belluti, F.; Gobbi, S.; Andrisano, V.; Ligresti, A.; Di Marzo, V. The first dual ChE/FAAH inhibitors: New perspectives for Alzheimer’s disease? ACS Med. Chem. Lett., 2012, 3(3), 182-186.
[http://dx.doi.org/10.1021/ml200313p] [PMID: 24900454]
[15]
Schneider, L.S.; Mangialasche, F.; Andreasen, N.; Feldman, H.; Giacobini, E.; Jones, R.; Mantua, V.; Mecocci, P.; Pani, L.; Winblad, B.; Kivipelto, M. Clinical trials and late-stage drug development for Alzheimer’s disease: An appraisal from 1984 to 2014. J. Intern. Med., 2014, 275(3), 251-283.
[http://dx.doi.org/10.1111/joim.12191] [PMID: 24605808]
[16]
Ghafary, S.; Najafi, Z.; Mohammadi-Khanaposhtani, M.; Nadri, H.; Edraki, N.; Ayashi, N.; Larijani, B.; Amini, M.; Mahdavi, M. Novel cinnamic acid-tryptamine hybrids as potent butyrylcholinesterase inhibitors: Synthesis, biological evaluation, and docking study. Arch. Pharm. (Weinheim), 2018, 351(10), e1800115.
[http://dx.doi.org/10.1002/ardp.201800115] [PMID: 30284339]
[17]
Skrzypek, A.; Matysiak, J.; Niewiadomy, A.; Bajda, M. Szymaski, P. Synthesis and biological evaluation of 1,3,4-thiadiazole analogues as novel AChE and BuChE inhibitors. Eur. J. Med. Chem., 2013, 62, 311-319.
[http://dx.doi.org/10.1016/j.ejmech.2012.12.060] [PMID: 23376249]
[18]
Mesulam, M.M.; Guillozet, A.; Shaw, P.; Levey, A.; Duysen, E.G.; Lockridge, O. Acetylcholinesterase knockouts establish central cholin-ergic pathways and can use butyrylcholinesterase to hydrolyze acetylcholine. Neuroscience, 2002, 110(4), 627-639.
[19]
Dong, J.; Atwood, C.S.; Anderson, V.E.; Siedlak, S.L.; Smith, M.A.; Perry, G.; Carey, P.R. Metal binding and oxidation of amyloid-β with-in isolated senile plaque cores: Raman microscopic evidence. Biochemistry, 2003, 42(10), 2768-2773.
[http://dx.doi.org/10.1021/bi0272151] [PMID: 12627941]
[20]
Horton, W.; Sood, A.; Peerannawar, S.; Kugyela, N.; Kulkarni, A.; Tulsan, R.; Tran, C.D.; Soule, J.; LeVine, H., III; Török, B.; Török, M. Synthesis and application of -carbolines as novel multi-functional anti-Alzheimer’s disease agents. Bioorg. Med. Chem. Lett., 2017, 27(2), 232-236.
[http://dx.doi.org/10.1016/j.bmcl.2016.11.067] [PMID: 27923619]
[21]
Huang, Y.; Mucke, L. Alzheimer mechanisms and therapeutic strategies. Cell, 2012, 148(6), 1204-1222.
[http://dx.doi.org/10.1016/j.cell.2012.02.040] [PMID: 22424230]
[22]
Dias, K.S.; Viegas, C., Jr Multi-target directed drugs: A modern approach for design of new drugs for the treatment of Alzheimer’s dis-ease. Curr. Neuropharmacol., 2014, 12(3), 239-255.
[http://dx.doi.org/10.2174/1570159X1203140511153200] [PMID: 24851088]
[23]
Xie, Y.; Wang, Y.; Jiang, S.; Xiang, X.; Wang, J.; Ning, L. Novel strategies for the fight of Alzheimer’s disease targeting amyloid-β protein. J. Drug Target., 2021, 1-10. Epub ahead of print
[http://dx.doi.org/10.1080/1061186X.2021.1973482] [PMID: 34435898]
[24]
Fang, L.; Gou, S.; Fang, X.; Cheng, L.; Fleck, C. Current progresses of novel natural products and their derivatives/analogs as anti-Alzheimer candidates: An update. Mini Rev. Med. Chem., 2013, 13(6), 870-887.
[http://dx.doi.org/10.2174/1389557511313060009] [PMID: 23305400]
[25]
Girek, M. Szymaski, P. Tacrine hybrids as multi-target-directed ligands in Alzheimer’s disease: Influence of chemical structures on biological activities. Chem. Pap., 2019, 73(2), 269-289.
[http://dx.doi.org/10.1007/s11696-018-0590-8]
[26]
Ayton, S.; Lei, P.; Bush, A.I. Metallostasis in Alzheimer’s disease. Free Radic. Biol. Med., 2013, 62, 76-89.
[http://dx.doi.org/10.1016/j.freeradbiomed.2012.10.558] [PMID: 23142767]
[27]
Citron, M. Alzheimer’s disease: Strategies for disease modification. Nat. Rev. Drug Discov., 2010, 9(5), 387-398.
[http://dx.doi.org/10.1038/nrd2896] [PMID: 20431570]
[28]
Bachurin, S.O.; Shevtsova, E.F.; Makhaeva, G.F.; Grigoriev, V.V.; Boltneva, N.P.; Kovaleva, N.V.; Lushchekina, S.V.; Shevtsov, P.N.; Neganova, M.E.; Redkozubova, O.M.; Bovina, E.V.; Gabrelyan, A.V.; Fisenko, V.P.; Sokolov, V.B.; Aksinenko, A.Y.; Echeverria, V.; Barreto, G.E.; Aliev, G. Novel conjugates of aminoadamantanes with carbazole derivatives as potential multitarget agents for AD treatment. Sci. Rep., 2017, 7(1), 45627.
[http://dx.doi.org/10.1038/srep45627] [PMID: 28358144]
[29]
Saturnino, C.; Iacopetta, D.; Sinicropi, M.S.; Rosano, C.; Caruso, A.; Caporale, A.; Marra, N.; Marengo, B.; Pronzato, M.A.; Parisi, O.I.; Longo, P.; Ricciarelli, R. N-alkyl carbazole derivatives as new tools for Alzheimer’s disease: Preliminary studies. Molecules, 2014, 19(7), 9307-9317.
[http://dx.doi.org/10.3390/molecules19079307] [PMID: 24991761]
[30]
Kihara, T.; Shimohama, S. Alzheimer’s disease and acetylcholine receptors. Acta Neurobiol. Exp. (Warsz.), 2004, 64(1), 99-105.
[PMID: 15190684]
[31]
John, V.; Beck, J.P.; Bienkowski, M.J.; Sinha, S.; Heinrikson, R.L. Human β-secretase (BACE) and BACE inhibitors. J. Med. Chem., 2003, 46(22), 4625-4630.
[http://dx.doi.org/10.1021/jm030247h] [PMID: 14561080]
[32]
Zhu, X.; Raina, A.K.; Perry, G.; Smith, M.A. Apoptosis in Alzheimer disease: A mathematical improbability. Curr. Alzheimer Res., 2006, 3(4), 393-396.
[http://dx.doi.org/10.2174/156720506778249470] [PMID: 17017869]
[33]
Haass, C.; Selkoe, D.J. Cellular processing of β-amyloid precursor protein and the genesis of amyloid β-peptide. Cell, 1993, 75(6), 1039-1042.
[http://dx.doi.org/10.1016/0092-8674(93)90312-E] [PMID: 8261505]
[34]
De Strooper, B. Aph-1, Pen-2, and nicastrin with presenilin generate an active γ-secretase complex. Neuron, 2003, 38(1), 9-12.
[http://dx.doi.org/10.1016/S0896-6273(03)00205-8] [PMID: 12691659]
[35]
Hardy, J.; Selkoe, D.J. The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science, 2002, 297(5580), 353-356.
[36]
Rosini, M.; Simoni, E.; Bartolini, M.; Cavalli, A.; Ceccarini, L.; Pascu, N.; McClymont, D.W.; Tarozzi, A.; Bolognesi, M.L.; Minarini, A.; Tumiatti, V.; Andrisano, V.; Mellor, I.R.; Melchiorre, C. Inhibition of acetylcholinesterase, β-amyloid aggregation, and NMDA receptors in Alzheimer’s disease: A promising direction for the multi-target-directed ligands gold rush. J. Med. Chem., 2008, 51(15), 4381-4384.
[http://dx.doi.org/10.1021/jm800577j] [PMID: 18605718]
[37]
Riepe, M.W.; Adler, G.; Ibach, B.; Weinkauf, B.; Gunay, I.; Tracik, F. Adding memantine to rivastigmine therapy in patients with mild-to-moderate Alzheimer’s disease: Results of a 12-week, open-label pilot study. Prim. Care Companion J. Clin. Psychiatry, 2006, 8(5), 258-263.
[http://dx.doi.org/10.4088/PCC.v08n0501] [PMID: 17235381]
[38]
Cummings, J.L.; Morstorf, T.; Zhong, K. Alzheimer’s disease drug-development pipeline: Few candidates, frequent failures. Alzheimers Res. Ther., 2014, 6(4), 37.
[http://dx.doi.org/10.1186/alzrt269] [PMID: 25024750]
[39]
Pepeu, G.; Giovannini, M.G. Cholinesterase inhibitors and beyond. Curr. Alzheimer Res., 2009, 6(2), 86-96.
[http://dx.doi.org/10.2174/156720509787602861] [PMID: 19355843]
[40]
Medina-Franco, J.L.; Giulianotti, M.A.; Welmaker, G.S.; Houghten, R.A. Shifting from the single to the multitarget paradigm in drug dis-covery. Drug Discov. Today, 2013, 18(9-10), 495-501.
[http://dx.doi.org/10.1016/j.drudis.2013.01.008] [PMID: 23340113]
[41]
Kumar, N.; Singh, K.K.; Luthra, P.M. A review on anticancer potential of some pyranocarabzole alkaloids and its derivatives. Int. J. Adv. Res. (Indore), 2021, 6(9), 874-883.
[http://dx.doi.org/10.21474/IJAR01/13091]
[42]
Luthra, P.M.; Kumar, N. Progress and development of C-3, C-6, and N-9 position substituted carbazole integrated molecular hybrid mole-cules as potential anticancer agents. Mini Rev. Med. Chem., 2021, 21(19), 2929-2956.
[http://dx.doi.org/10.2174/1389557521666210521221808] [PMID: 34036916]
[43]
Burckhalter, J.H.; Stephens, V.C.; Hall, L.A. Antihistaminics: The N-beta-dimethylaminoethyl derivatives of carbazole and diphenylamine. J. Am. Pharm. Assoc., 1950, 39(5), 271-273.
[http://dx.doi.org/10.1002/jps.3030390508] [PMID: 15421917]
[44]
Tsutsumi, L.S.; Gündisch, D.; Sun, D. Carbazole scaffold in medicinal chemistry and natural products: A review from 2010-2015. Curr. Top. Med. Chem., 2016, 16(11), 1290-1313.
[http://dx.doi.org/10.2174/1568026615666150915112647] [PMID: 26369811]
[45]
Bashir, M.; Bano, A.; Ijaz, A.S.; Chaudhary, B.A. Recent developments and biological activities of N-substituted carbazole derivatives: A review. Molecules, 2015, 20(8), 13496-13517.
[http://dx.doi.org/10.3390/molecules200813496] [PMID: 26213906]
[46]
Clausen, J.D.; Kjellerup, L.; Cohrt, K.O.; Hansen, J.B.; Dalby-Brown, W.; Winther, A.L. Elucidation of antimicrobial activity and mecha-nism of action by N-substituted carbazole derivatives. Bioorg. Med. Chem. Lett., 2017, 27(19), 4564-4570.
[http://dx.doi.org/10.1016/j.bmcl.2017.08.067] [PMID: 28893470]
[47]
Kumar, N.; Lal, N.; Nemaysh, V.; Luthra, P.M. Design, synthesis, DNA binding studies and evaluation of anticancer potential of novel substituted biscarbazole derivatives against human glioma U87 MG cell line. Bioorg. Chem., 2020, 100, 103911.
[http://dx.doi.org/10.1016/j.bioorg.2020.103911] [PMID: 32502918]
[48]
Kumar, N.; Kumar, R.; Nemaysh, V.; Lal, N.; Luthra, P.M. Bis ((1, 4-dimethyl-9 H-carbazol-3-yl) methyl) amine-mediated anticancer effect triggered by sequence-specific cleavage of DNA leading to programmed cell death in the human U87 cell line. RSC Advances, 2016, 6(72), 67925-67940.
[http://dx.doi.org/10.1039/C6RA12999D]
[49]
Issa, S.; Prandina, A.; Bedel, N.; Rongved, P.; Yous, S.; Le Borgne, M.; Bouaziz, Z. Carbazole scaffolds in cancer therapy: A review from 2012 to 2018. J. Enzyme Inhib. Med. Chem., 2019, 34(1), 1321-1346.
[http://dx.doi.org/10.1080/14756366.2019.1640692] [PMID: 31328585]
[50]
Caruso, A.; Ceramella, J.; Iacopetta, D.; Saturnino, C.; Mauro, M.V.; Bruno, R.; Aquaro, S.; Sinicropi, M.S. Carbazole derivatives as antivi-ral agents: An overview. Molecules, 2019, 24(10), 1912.
[http://dx.doi.org/10.3390/molecules24101912] [PMID: 31109016]
[51]
Ghobadian, R.; Nadri, H.; Moradi, A.; Bukhari, S.N.A.; Mahdavi, M.; Asadi, M.; Akbarzadeh, T.; Khaleghzadeh-Ahangar, H.; Sharifzadeh, M.; Amini, M. Design, synthesis, and biological evaluation of selective and potent Carbazole-based butyrylcholinesterase inhibitors. Bioorg. Med. Chem., 2018, 26(17), 4952-4962.
[http://dx.doi.org/10.1016/j.bmc.2018.08.035] [PMID: 30190181]
[52]
Saengkhae, C.; Salerno, M.; Adès, D.; Siove, A.; Le Moyec, L.; Migonney, V.; Garnier-Suillerot, A. Ability of carbazole salts, inhibitors of Alzheimer β-amyloid fibril formation, to cross cellular membranes. Eur. J. Pharmacol., 2007, 559(2-3), 124-131.
[http://dx.doi.org/10.1016/j.ejphar.2007.01.005] [PMID: 17291491]
[53]
Wu, X.; Kosaraju, J.; Zhou, W.; Tam, K.Y. Neuroprotective effect of SLM, a novel carbazole-based fluorophore, on SH-SY5Y cell model and 3xTg-AD mouse model of Alzheimer’s disease. ACS Chem. Neurosci., 2017, 8(3), 676-685.
[http://dx.doi.org/10.1021/acschemneuro.6b00388] [PMID: 28032988]
[54]
Shi, D.H.; Min, W.; Song, M.Q.; Si, X.X.; Li, M.C.; Zhang, Z.Y.; Liu, Y.W.; Liu, W.W. Synthesis, characterization, crystal structure and evaluation of four carbazole-coumarin hybrids as multifunctional agents for the treatment of Alzheimer’s disease. J. Mol. Struct., 2020, 1209, 127897.
[http://dx.doi.org/10.1016/j.molstruc.2020.127897]
[55]
Yang, W.; Wong, Y.; Ng, O.T.; Bai, L.P.; Kwong, D.W.; Ke, Y.; Jiang, Z.H.; Li, H.W.; Yung, K.K.; Wong, M.S. Inhibition of beta-amyloid peptide aggregation by multifunctional carbazole-based fluorophores. Angew. Chem. Int. Ed. Engl., 2012, 51(8), 1804-1810.
[http://dx.doi.org/10.1002/anie.201104150] [PMID: 22086555]
[56]
Tang, Y.Z.; Liu, Z.Q. Free-radical-scavenging effect of carbazole derivatives on AAPH-induced hemolysis of human erythrocytes. Bioorg. Med. Chem., 2007, 15(5), 1903-1913.
[http://dx.doi.org/10.1016/j.bmc.2007.01.007] [PMID: 17236778]
[57]
Karaaslan, C.; Ince, E.; Gurer-Orhan, H.; Tavakkoli, M.; Firuzi, O.; Saso, L.; Suzen, S. Behaviour of 9-ethyl-9H-carbazole hydrazone derivatives against oxidant systems: Protective effect on amyloid [beta]-induced damage. Croat. Chem. Acta, 2019, 92(1), 87-95.
[http://dx.doi.org/10.5562/cca3481]
[58]
Herlem, D.; Martin, M.T.; Thal, C.; Guillou, C. Synthesis and structure-activity relationships of open D-Ring galanthamine analogues. Bioorg. Med. Chem. Lett., 2003, 13(14), 2389-2391.
[http://dx.doi.org/10.1016/S0960-894X(03)00397-4] [PMID: 12824041]
[59]
Fang, L.; Fang, X.; Gou, S.; Lupp, A.; Lenhardt, I.; Sun, Y.; Huang, Z.; Chen, Y.; Zhang, Y.; Fleck, C. Design, synthesis and biological evaluation of D-ring opened galantamine analogs as multifunctional anti-Alzheimer agents. Eur. J. Med. Chem., 2014, 76, 376-386.
[http://dx.doi.org/10.1016/j.ejmech.2014.02.035] [PMID: 24594525]
[60]
Choubdar, N.; Golshani, M.; Jalili-Baleh, L.; Nadri, H.; Küçükkilinç, T.T.; Ayazgök, B.; Moradi, A.; Moghadam, F.H.; Abdolahi, Z.; Ameri, A.; Salehian, F.; Foroumadi, A.; Khoobi, M. New classes of carbazoles as potential multi-functional anti-Alzheimer’s agents. Bioorg. Chem., 2019, 91, 103164.
[http://dx.doi.org/10.1016/j.bioorg.2019.103164] [PMID: 31398601]
[61]
Lysko, P.G.; Webb, C.L.; Gu, J.L.; Ohlstein, E.H.; Ruffolo, R.R., Jr; Yue, T.L. A comparison of carvedilol and metoprolol antioxidant activities in vitro. J. Cardiovasc. Pharmacol., 2000, 36(2), 277-281.
[http://dx.doi.org/10.1097/00005344-200008000-00020] [PMID: 10942172]
[62]
Zhu, Y.; Xiao, K.; Ma, L.; Xiong, B.; Fu, Y.; Yu, H.; Wang, W.; Wang, X.; Hu, D.; Peng, H.; Li, J.; Gong, Q.; Chai, Q.; Tang, X.; Zhang, H.; Li, J.; Shen, J. Design, synthesis and biological evaluation of novel dual inhibitors of acetylcholinesterase and β-secretase. Bioorg. Med. Chem., 2009, 17(4), 1600-1613.
[http://dx.doi.org/10.1016/j.bmc.2008.12.067] [PMID: 19162488]
[63]
Gontijo, V.S.; Viegas, F.P.D.; Ortiz, C.J.C.; de Freitas Silva, M.; Damasio, C.M.; Rosa, M.C.; Campos, T.G.; Couto, D.S.; Tranches Dias, K.S.; Viegas, C. Molecular hybridization as a tool in the design of multi-target directed drug candidates for neurodegenerative diseases. Curr. Neuropharmacol., 2020, 18(5), 348-407.
[http://dx.doi.org/10.2174/1385272823666191021124443] [PMID: 31631821]
[64]
Lipton, S.A. Paradigm shift in neuroprotection by NMDA receptor blockade: Memantine and beyond. Nat. Rev. Drug Discov., 2006, 5(2), 160-170.
[http://dx.doi.org/10.1038/nrd1958] [PMID: 16424917]
[65]
Morphy, R.; Rankovic, Z. Designed multiple ligands. An emerging drug discovery paradigm. J. Med. Chem., 2005, 48(21), 6523-6543.
[http://dx.doi.org/10.1021/jm058225d] [PMID: 16220969]
[66]
Simoni, E.; Bartolini, M.; Abu, I.F.; Blockley, A.; Gotti, C.; Bottegoni, G.; Caporaso, R.; Bergamini, C.; Andrisano, V.; Cavalli, A.; Mellor, I.R.; Minarini, A.; Rosini, M. Multitarget drug design strategy in Alzheimer’s disease: Focus on cholinergic transmission and amyloid-β aggregation. Future Med. Chem., 2017, 9(10), 953-963.
[http://dx.doi.org/10.4155/fmc-2017-0039] [PMID: 28632446]
[67]
Shalini, K.V.; Kumar, V. Have molecular hybrids delivered effective anti-cancer treatments and what should future drug discovery focus on? Expert Opin. Drug Discov., 2021, 16(4), 335-363.
[http://dx.doi.org/10.1080/17460441.2021.1850686] [PMID: 33305635]
[68]
Bolognesi, M.L. Polypharmacology in a single drug: Multitarget drugs. Curr. Med. Chem., 2013, 20(13), 1639-1645.
[http://dx.doi.org/10.2174/0929867311320130004] [PMID: 23410164]
[69]
Cavalli, A.; Bolognesi, M.L.; Minarini, A.; Rosini, M.; Tumiatti, V.; Recanatini, M.; Melchiorre, C. Multi-target-directed ligands to combat neurodegenerative diseases. J. Med. Chem., 2008, 51(3), 347-372.
[http://dx.doi.org/10.1021/jm7009364] [PMID: 18181565]
[70]
Zhan, P.; Liu, X. Rationally designed multitarget anti-HIV agents. Curr. Med. Chem., 2013, 20(13), 1743-1758.
[http://dx.doi.org/10.2174/0929867311320130011] [PMID: 23410170]
[71]
Rosini, M. Polypharmacology: The rise of multitarget drugs over combination therapies. Future Med. Chem., 2014, 6(5), 485-487.
[http://dx.doi.org/10.4155/fmc.14.25] [PMID: 24649950]
[72]
Darghal, N.; Garnier-Suillerot, A.; Salerno, M. Mechanism of thioflavin T accumulation inside cells overexpressing P-glycoprotein or multidrug resistance-associated protein: Role of lipophilicity and positive charge. Biochem. Biophys. Res. Commun., 2006, 343(2), 623-629.
[http://dx.doi.org/10.1016/j.bbrc.2006.03.024] [PMID: 16554036]
[73]
Mishra, C.B.; Kumari, S.; Tiwari, M. Thiazole: A promising heterocycle for the development of potent CNS active agents. Eur. J. Med. Chem., 2015, 92, 1-34.
[http://dx.doi.org/10.1016/j.ejmech.2014.12.031] [PMID: 25544146]
[74]
Rosini, M.; Andrisano, V.; Bartolini, M.; Bolognesi, M.L.; Hrelia, P.; Minarini, A.; Tarozzi, A.; Melchiorre, C. Rational approach to dis-cover multipotent anti-Alzheimer drugs. J. Med. Chem., 2005, 48(2), 360-363.
[http://dx.doi.org/10.1021/jm049112h] [PMID: 15658850]
[75]
Asso, V. Ghilardi, E.; Bertini, S.; Digiacomo, M.; Granchi, C.; Minutolo, F.; Rapposelli, S.; Bortolato, A.; Moro, S.; Macchia, M. α-Naphthylaminopropan-2-ol derivatives as BACE1 inhibitors. ChemMedChem, 2008, 3(10), 1530-1534.
[http://dx.doi.org/10.1002/cmdc.200800162] [PMID: 18781572]
[76]
Porcari, V.; Magnoni, L.; Terstappen, G.C.; Fecke, W. A continuous time-resolved fluorescence assay for identification of BACE1 inhibi-tors. Assay Drug Dev. Technol., 2005, 3(3), 287-297.
[http://dx.doi.org/10.1089/adt.2005.3.287] [PMID: 15971990]
[77]
Bertini, S.; Asso, V.; Ghilardi, E.; Granchi, C.; Manera, C.; Minutolo, F.; Saccomanni, G.; Bortolato, A.; Mason, J.; Moro, S.; Macchia, M. Carbazole-containing arylcarboxamides as BACE1 inhibitors. Bioorg. Med. Chem. Lett., 2011, 21(22), 6657-6661.
[http://dx.doi.org/10.1016/j.bmcl.2011.09.064] [PMID: 21986588]
[78]
Thiratmatrakul, S.; Yenjai, C.; Waiwut, P.; Vajragupta, O.; Reubroycharoen, P.; Tohda, M.; Boonyarat, C. Synthesis, biological evaluation and molecular modeling study of novel tacrine-carbazole hybrids as potential multifunctional agents for the treatment of Alzheimer’s dis-ease. Eur. J. Med. Chem., 2014, 75, 21-30.
[http://dx.doi.org/10.1016/j.ejmech.2014.01.020] [PMID: 24508831]
[79]
Songsiang, U.; Thongthoom, T.; Zeekpudsa, P.; Kukongviriyapan, V.; Boonyarat, C.; Wangboonskul, J.; Yenjai, C. Antioxidant activity and cytotoxicity against cholangiocarcinoma of carbazoles and coumarins from Clausena harmandiana. Sci. Asia, 2012, 38(1), 75-81.
[http://dx.doi.org/10.2306/scienceasia1513-1874.2012.38.075]
[80]
Kozurkova, M.; Hamulakova, S.; Gazova, Z.; Paulikova, H.; Kristian, P. Neuroactive multifunctional tacrine congeners with cholinester-ase, anti-amyloid aggregation and neuroprotective properties. Pharmaceuticals (Basel), 2011, 4(2), 382-418.
[http://dx.doi.org/10.3390/ph4020382]
[81]
Zhu, D.; Chen, M.; Li, M.; Luo, B.; Zhao, Y.; Huang, P.; Xue, F.; Rapposelli, S.; Pi, R.; Wen, S. Discovery of novel N-substituted carba-zoles as neuroprotective agents with potent anti-oxidative activity. Eur. J. Med. Chem., 2013, 68, 81-88.
[http://dx.doi.org/10.1016/j.ejmech.2013.07.029] [PMID: 23973819]
[82]
Picone, P.; Bondi, M.L.; Montana, G.; Bruno, A.; Pitarresi, G.; Giammona, G.; Di Carlo, M.; Giammona, G.; Di Carlo, M. Ferulic acid in-hibits oxidative stress and cell death induced by Ab oligomers: Improved delivery by solid lipid nanoparticles. Free Radic. Res., 2009, 43(11), 1133-1145.
[http://dx.doi.org/10.1080/10715760903214454] [PMID: 19863373]
[83]
Fang, L.; Chen, M.; Liu, Z.; Fang, X.; Gou, S.; Chen, L. Ferulic acid-carbazole hybrid compounds: Combination of cholinesterase inhibi-tion, antioxidant and neuroprotection as multifunctional anti-Alzheimer agents. Bioorg. Med. Chem., 2016, 24(4), 886-893.
[http://dx.doi.org/10.1016/j.bmc.2016.01.010] [PMID: 26795115]
[84]
Ceccom, J.; Coslédan, F.; Halley, H.; Francès, B.; Lassalle, J.M.; Meunier, B. Copper chelator induced efficient episodic memory recovery in a non-transgenic Alzheimer’s mouse model. PLoS One, 2012, 7(8), e43105.
[http://dx.doi.org/10.1371/journal.pone.0043105]
[85]
Robert, A.; Liu, Y.; Nguyen, M.; Meunier, B. Regulation of copper and iron homeostasis by metal chelators: A possible chemotherapy for Alzheimer’s disease. Acc. Chem. Res., 2015, 48(5), 1332-1339.
[http://dx.doi.org/10.1021/acs.accounts.5b00119] [PMID: 25946460]
[86]
Nguyen, M.; Robert, A.; Sournia-Saquet, A.; Vendier, L.; Meunier, B. Characterization of new specific copper chelators as potential drugs for the treatment of Alzheimer’s disease. Chemistry, 2014, 20(22), 6771-6785.
[http://dx.doi.org/10.1002/chem.201402143] [PMID: 24797103]
[87]
Bandgar, B.P.; Adsul, L.K.; Lonikar, S.V.; Chavan, H.V.; Shringare, S.N.; Patil, S.A.; Jalde, S.S.; Koti, B.A.; Dhole, N.A.; Gacche, R.N.; Shirfule, A. Synthesis of novel carbazole chalcones as radical scavenger, antimicrobial and cancer chemopreventive agents. J. Enzyme Inhib. Med. Chem., 2013, 28(3), 593-600.
[http://dx.doi.org/10.3109/14756366.2012.663365] [PMID: 22380776]
[88]
Verma, G.; Marella, A.; Shaquiquzzaman, M.; Akhtar, M.; Ali, M.R.; Alam, M.M. A review exploring biological activities of hydrazones. J. Pharm. Bioallied Sci., 2014, 6(2), 69-80.
[http://dx.doi.org/10.4103/0975-7406.129170] [PMID: 24741273]
[89]
Puskullu, M.O.; Shirinzadeh, H.; Nenni, M.; Gurer-Orhan, H.; Suzen, S. Synthesis and evaluation of antioxidant activity of new quinoline-2-carbaldehyde hydrazone derivatives: Bioisosteric melatonin analogues. J. Enzyme Inhib. Med. Chem., 2016, 31(1), 121-125.
[http://dx.doi.org/10.3109/14756366.2015.1005012] [PMID: 25942363]
[90]
Ylmaz, A.D.; Coban, T.; Suzen, S. Synthesis and antioxidant activity evaluations of melatonin-based analogue indole-hydrazide/hydrazone derivatives. J. Enzyme Inhib. Med. Chem., 2012, 27(3), 428-436.
[http://dx.doi.org/10.3109/14756366.2011.594048] [PMID: 21740102]
[91]
Cacabelos, R. Have there been improvements in Alzheimer’s disease drug discovery over the past 5 years? Expert Opin. Drug Discov., 2018, 13(6), 523-538.
[http://dx.doi.org/10.1080/17460441.2018.1457645] [PMID: 29607687]
[92]
Patel, D.V.; Patel, N.R.; Kanhed, A.M.; Teli, D.M.; Patel, K.B.; Joshi, P.D.; Patel, S.P.; Gandhi, P.M.; Chaudhary, B.N.; Prajapati, N.K.; Patel, K.V.; Yadav, M.R. Novel carbazole-stilbene hybrids as multifunctional anti-Alzheimer agents. Bioorg. Chem., 2020, 101, 103977.
[http://dx.doi.org/10.1016/j.bioorg.2020.103977] [PMID: 32485470]
[93]
Hong, M.C.; Kim, Y.K.; Choi, J.Y.; Yang, S.Q.; Rhee, H.; Ryu, Y.H.; Choi, T.H.; Cheon, G.J.; An, G.I.; Kim, H.Y.; Kim, Y.; Kim, D.J.; Lee, J.S.; Chang, Y.T.; Lee, K.C. Synthesis and evaluation of stilbene derivatives as a potential imaging agent of amyloid plaques. Bioorg. Med. Chem., 2010, 18(22), 7724-7730.
[http://dx.doi.org/10.1016/j.bmc.2010.06.044] [PMID: 20621493]
[94]
Lu, C.; Guo, Y.; Li, J.; Yao, M.; Liao, Q.; Xie, Z.; Li, X. Design, synthesis, and evaluation of resveratrol derivatives as Aß(;-;;) aggrega-tion inhibitors, antioxidants, and neuroprotective agents. Bioorg. Med. Chem. Lett., 2012, 22(24), 7683-7687.
[http://dx.doi.org/10.1016/j.bmcl.2012.09.105] [PMID: 23127891]
[95]
Singh, N.; Agrawal, M.; Doré, S. Neuroprotective properties and mechanisms of resveratrol in in vitro and in vivo experimental cerebral stroke models. ACS Chem. Neurosci., 2013, 4(8), 1151-1162.
[http://dx.doi.org/10.1021/cn400094w] [PMID: 23758534]
[96]
Azman, N.A.; Gordon, M.H.; Skowyra, M.; Segovia, F.; Almajano, M.P. Antioxidant properties of resveratrol: A structure-activity insight. J. Sci. Food Agric., 2015, 95, 210-218.
[97]
Patel, D.V.; Patel, N.R.; Kanhed, A.M.; Patel, S.P.; Sinha, A.; Kansara, D.D.; Mecwan, A.R.; Patel, S.B.; Upadhyay, P.N.; Patel, K.B.; Shah, D.B.; Prajapati, N.K.; Murumkar, P.R.; Patel, K.V.; Yadav, M.R. Novel multitarget directed triazinoindole derivatives as anti-Alzheimer agents. ACS Chem. Neurosci., 2019, 10(8), 3635-3661.
[http://dx.doi.org/10.1021/acschemneuro.9b00226] [PMID: 31310717]
[98]
Najafi, Z.; Mahdavi, M.; Saeedi, M.; Karimpour-Razkenari, E.; Edraki, N.; Sharifzadeh, M.; Khanavi, M.; Akbarzadeh, T. Novel tacrine-coumarin hybrids linked to 1,2,3-triazole as anti-Alzheimer’s compounds: In vitro and in vivo biological evaluation and docking study. Bioorg. Chem., 2019, 83, 303-316.
[http://dx.doi.org/10.1016/j.bioorg.2018.10.056] [PMID: 30396115]
[99]
Wang, Z.M.; Cai, P.; Liu, Q.H.; Xu, D.Q.; Yang, X.L.; Wu, J.J.; Kong, L.Y.; Wang, X.B. Rational modification of donepezil as multifunc-tional acetylcholinesterase inhibitors for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2016, 123, 282-297.
[http://dx.doi.org/10.1016/j.ejmech.2016.07.052] [PMID: 27484514]
[100]
Hiremathad, A.; Chand, K.; Keri, R.S. Development of coumarin-benzofuran hybrids as versatile multitargeted compounds for the treat-ment of Alzheimer’s Disease. Chem. Biol. Drug Des., 2018, 92(2), 1497-1503.
[http://dx.doi.org/10.1111/cbdd.13316] [PMID: 29679445]
[101]
Sun, Q.; Peng, D.Y.; Yang, S.G.; Zhu, X.L.; Yang, W.C.; Yang, G.F. Syntheses of coumarin-tacrine hybrids as dual-site acetylcholinester-ase inhibitors and their activity against butylcholinesterase, Aβ aggregation, and β-secretase. Bioorg. Med. Chem., 2014, 22(17), 4784-4791.
[http://dx.doi.org/10.1016/j.bmc.2014.06.057] [PMID: 25088549]
[102]
Catto, M.; Pisani, L.; Leonetti, F.; Nicolotti, O.; Pesce, P.; Stefanachi, A.; Cellamare, S.; Carotti, A. Design, synthesis and biological evalua-tion of coumarin alkylamines as potent and selective dual binding site inhibitors of acetylcholinesterase. Bioorg. Med. Chem., 2013, 21(1), 146-152.
[http://dx.doi.org/10.1016/j.bmc.2012.10.045] [PMID: 23199476]
[103]
Luo, Z.; Sheng, J.; Sun, Y.; Lu, C.; Yan, J.; Liu, A.; Luo, H.B.; Huang, L.; Li, X. Synthesis and evaluation of multi-target-directed ligands against Alzheimer’s disease based on the fusion of donepezil and ebselen. J. Med. Chem., 2013, 56(22), 9089-9099.
[http://dx.doi.org/10.1021/jm401047q] [PMID: 24160297]
[104]
Wang, J.; Wang, Z.M.; Li, X.M.; Li, F.; Wu, J.J.; Kong, L.Y.; Wang, X.B. Synthesis and evaluation of multi-target-directed ligands for the treatment of Alzheimer’s disease based on the fusion of donepezil and melatonin. Bioorg. Med. Chem., 2016, 24(18), 4324-4338.
[http://dx.doi.org/10.1016/j.bmc.2016.07.025] [PMID: 27460699]
[105]
Bautista-Aguilera, O.M.; Esteban, G.; Bolea, I.; Nikolic, K.; Agbaba, D.; Moraleda, I.; Iriepa, I.; Samadi, A.; Soriano, E.; Unzeta, M.; Marco-Contelles, J. Design, synthesis, pharmacological evaluation, QSAR analysis, molecular modeling and ADMET of novel donepezil-indolyl hybrids as multipotent cholinesterase/monoamine oxidase inhibitors for the potential treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2014, 75, 82-95.
[http://dx.doi.org/10.1016/j.ejmech.2013.12.028] [PMID: 24530494]
[106]
Łozińska, I.; Świerczyńska, A.; Molęda, Z.; Hartman, A.M.; Hirsch, A.K.H.; Czarnocki, Z. Donepezil-melatonin hybrids as butyrylcholinesterase inhibitors: Improving binding affinity through varying mode of linking fragments. Arch. Pharm. (Weinheim), 2018, 351(11) e1800194
[http://dx.doi.org/10.1002/ardp.201800194] [PMID: 30290008]
[107]
Shaikh, S.; Dhavan, P.; Singh, P.; Uparkar, J.; Vaidya, S.P.; Jadhav, B.L.; Ramana, M.V. Synthesis of carbazole based α-aminophosphonate derivatives: Design, molecular docking and in vitro cholinesterase activity. J. Biomol. Struct. Dyn., 2020, 2020, 1-23.
[http://dx.doi.org/10.1080/07391102.2020.1861981] [PMID: 33345710]
[108]
Lejczak, B.; Kafarski, P.; Sztajer, H.; Mastalerz, P. Antibacterial activity of phosphono dipeptides related to alafosfalin. J. Med. Chem., 1986, 29(11), 2212-2217.
[http://dx.doi.org/10.1021/jm00161a014] [PMID: 3783584]
[109]
Sieńczyk, M.; Oleksyszyn, J. Irreversible inhibition of serine proteases - design and in vivo activity of diaryl α-aminophosphonate deriva-tives. Curr. Med. Chem., 2009, 16(13), 1673-1687.
[http://dx.doi.org/10.2174/092986709788186246] [PMID: 19442139]
[110]
Mulla, S.A.; Pathan, M.Y.; Chavan, S.S.; Gample, S.P.; Sarkar, D. Highly efficient one-pot multi-component synthesis of α-aminophosphonates and bis--aminophosphonates catalyzed by heterogeneous reusable silica supported dodecatungstophosphoric acid (DTP/SiO2) at ambient temperature and their antitubercular evaluation against Mycobactrium Tuberculosis. RSC Advances, 2014, 4(15), 7666-7672.
[http://dx.doi.org/10.1039/c3ra45853a]
[111]
Sudileti, M.; Chintha, V.; Nagaripati, S.; Gundluru, M.; Yasmin, S.H.; Wudayagiri, R.; Cirandur, S.R. Green synthesis, molecular docking, anti-oxidant and anti-inflammatory activities of α-aminophosphonates. Med. Chem. Res., 2019, 28(10), 1740-1754.
[http://dx.doi.org/10.1007/s00044-019-02411-8]
[112]
Xie, D.; Zhang, A.; Liu, D.; Yin, L.; Wan, J.; Zeng, S.; Hu, D. Synthesis and antiviral activity of novel α-aminophosphonates containing 6-fluorobenzothiazole moiety. Phosphorus Sulfur Silicon Relat. Elem., 2017, 192(9), 1061-1067.
[http://dx.doi.org/10.1080/10426507.2017.1323895]
[113]
Shaikh, S.; Dhavan, P.; Pavale, G.; Ramana, M.M.V.; Jadhav, B.L. Design, synthesis and evaluation of pyrazole bearing α-aminophosphonate derivatives as potential acetylcholinesterase inhibitors against Alzheimer’s disease. Bioorg. Chem., 2020, 96, 103589.
[http://dx.doi.org/10.1016/j.bioorg.2020.103589] [PMID: 31978679]
[114]
Barut, B. Kele T.; Biyiklioglu, Z.; Yalçn, C.Ö. Peripheral or nonperipheral tetra;[4;(9H;carbazol;9;yl) phenoxy] substituted cobalt (II), manganese (III) phthalocyanines: Synthesis, acetylcholinesterase, butyrylcholinesterase, and ;glucosidase inhibitory effects and anti-cancer activities. Appl. Organomet. Chem., 2021, 35(1), e6021.
[http://dx.doi.org/10.1002/aoc.6021]
[115]
Günsel, A.; Bilgicli, A.T.; Kandemir, C.; Sancak, R.; Arabaci, G.; Yarasir, M.N. Comparison of novel tetra-substituted phthalocyanines with their quaternized derivatives: Antioxidant and antibacterial properties. Synth. Met., 2020, 260, 116288.
[http://dx.doi.org/10.1016/j.synthmet.2019.116288]
[116]
Pikin, M.; Öztürk, Ö.F.; Odaba Z. Determination of photophysical, photochemical and spectroscopic properties of novel lead (II) phthalocyanines. Polyhedron, 2020, 182, 114480.
[http://dx.doi.org/10.1016/j.poly.2020.114480]
[117]
Peng, X.H.; Chen, S.F.; Zheng, B.Y.; Zheng, B.D.; Zheng, Q.F.; Li, X.S.; Ke, M.R.; Huang, J.D. Comparison between amine-terminated phthalocyanines and their chlorambucil conjugates: Synthesis, spectroscopic properties, and in vitro anticancer activity. Tetrahedron, 2017, 73(4), 378-384.
[http://dx.doi.org/10.1016/j.tet.2016.12.017]
[118]
Shuai, L.; Wang, S.; Zhang, L.; Fu, B.; Zhou, X. Cationic porphyrins and analogues as new DNA topoisomerase I and II inhibitors. Chem. Biodivers., 2009, 6(6), 827-837.
[http://dx.doi.org/10.1002/cbdv.200800083] [PMID: 19551725]
[119]
de Souza, L.G.; Rennã, M.N.; Figueroa-Villar, J.D. Coumarins as cholinesterase inhibitors: A review. Chem. Biol. Interact., 2016, 254, 11-23.
[http://dx.doi.org/10.1016/j.cbi.2016.05.001] [PMID: 27174134]
[120]
Ibrar, A.; Shehzadi, S.A.; Saeed, F.; Khan, I. Developing hybrid molecule therapeutics for diverse enzyme inhibitory action: Active role of coumarin-based structural leads in drug discovery. Bioorg. Med. Chem., 2018, 26(13), 3731-3762.
[http://dx.doi.org/10.1016/j.bmc.2018.05.042] [PMID: 30017112]
[121]
Singh, H.; Singh, J.V.; Bhagat, K.; Gulati, H.K.; Sanduja, M.; Kumar, N.; Kinarivala, N.; Sharma, S. Rational approaches, design strategies, structure activity relationship and mechanistic insights for therapeutic coumarin hybrids. Bioorg. Med. Chem., 2019, 27(16), 3477-3510.
[http://dx.doi.org/10.1016/j.bmc.2019.06.033] [PMID: 31255497]
[122]
Patel, K.B.; Patel, D.V.; Patel, N.R.; Kanhed, A.M.; Teli, D.M.; Gandhi, B.; Shah, B.S.; Chaudhary, B.N.; Prajapati, N.K.; Patel, K.V.; Yadav, M.R. Carbazole-based semicarbazones and hydrazones as multifunctional anti-Alzheimer agents. J. Biomol. Struct. Dyn., 2021, 2021, 1-22.
[http://dx.doi.org/10.1080/07391102.2021.1942212] [PMID: 34215173]
[123]
Prathima, B.; Rao, Y.S.; Chalapathi, P.V.; Reddy, Y.P.; Reddy, V. Spectral, structural and biological analysis of Cr (III) complex with ben-zyloxybenzaldehyde-4-phenyl-3-thiosemicarbazone. Int. J. Pharm. Pharm. Sci., 2012, 4, 167-174.
[124]
Mathew, B.; Baek, S.C.; Grace Thomas Parambi, D.; Pil Lee, J.; Joy, M.; Annie Rilda, P.R.; Randev, R.V.; Nithyamol, P.; Vijayan, V.; Inasu, S.T.; Mathew, G.E.; Lohidakshan, K.K.; Kumar Krishnan, G.; Kim, H. Selected aryl thiosemicarbazones as a new class of multi-targeted monoamine oxidase inhibitors. MedChemComm, 2018, 9(11), 1871-1881.
[http://dx.doi.org/10.1039/C8MD00399H] [PMID: 30568755]
[125]
Mishra, C.B.; Sharma, D.; Prakash, A.; Kumari, N.; Kumar, N.; Luthra, P.M. Design and synthesis of (4E)-4-(4-substitutedbenzyl-ideneamino)-3-substituted-2,3-dihydro-2-thioxothiazole-5-carbonitrile as novel A2A receptor antagonists. Bioorg. Med. Chem., 2013, 21(19), 6077-6083.
[http://dx.doi.org/10.1016/j.bmc.2013.07.005] [PMID: 23953686]
[126]
Mongre, R.K.; Mishra, C.B.; Prakash, A.; Jung, S.; Lee, B.S.; Kumari, S.; Hong, J.T.; Lee, M.S. Novel carbazole-piperazine hybrid small molecule induces apoptosis by targeting BCL-2 and inhibits tumor progression in lung adenocarcinoma in vitro and xenograft mice model. Cancers (Basel), 2019, 11(9), 1245.
[http://dx.doi.org/10.3390/cancers11091245] [PMID: 31450709]

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