Piperidine Nucleus as a Promising Scaffold for Alzheimer’s Disease: Current Landscape and Future Perspective

Page: [1221 - 1259] Pages: 39

  • * (Excluding Mailing and Handling)

Abstract

Heterocycles and their derivatives hold an important place in medicinal chemistry due to their vast therapeutic and pharmacological significance and wider implications in drug design and development. Piperidine is a nitrogen-containing heterocyclic moiety that exhibits an array of pharmacological properties. This review discusses the potential of piperidine derivatives against the neurodegenerative disease Alzheimer’s. The incidences of Alzheimer’s disease are increasing nowadays, and constant efforts are being made to develop a medicinal agent for this disease. We have highlighted the advancement in developing piperidine-based anti-neuronal disease compounds and the profound activities of some major piperidine-bearing drug molecules with their important target site.

This review focuses on advancements in the field of natural and synthetic occurring piperidines active against Alzheimer’s disease, with emphasis on the past 6 years. The discussion also includes the structure-activity relationship, the structures of the most promising molecules, and their biological activities against Alzheimer’s disease. The promising activities revealed by these piperidinebased scaffolds undoubtedly place them at the forefront of discovering prospective drug candidates. Thus, it would be of great interest to researchers working on synthesizing neuroprotective drug candidates.

Graphical Abstract

[1]
Hippius, H.; Neundörfer, G. The discovery of Alzheimer’s disease. Dialogues Clin. Neurosci., 2003, 5(1), 101-108.
[http://dx.doi.org/10.31887/DCNS.2003.5.1/hhippius] [PMID: 22034141]
[2]
Terracciano, A.; Sutin, A.R. Personality and Alzheimer’s disease: An integrative review. Pers. Disord., 2019, 10(1), 4-12.
[http://dx.doi.org/10.1037/per0000268] [PMID: 30604979]
[3]
Niu, H.; Alvarez-Alvarez, I.; Guillen-Grima, F.; Al-Rahamneh, M.J.; Aguinaga-Ontoso, I. Trends of mortality from Alzheimer’s disease in the European Union, 1994-2013. Eur. J. Neurol., 2017, 24(6), 858-866.
[http://dx.doi.org/10.1111/ene.13302] [PMID: 28544405]
[4]
Nichols, E.; Szoeke, C.E.I.; Vollset, S.E.; Abbasi, N.; Abd-Allah, F.; Abdela, J.; Aichour, M.T.E.; Akinyemi, R.O.; Alahdab, F.; Asgedom, S.W.; Awasthi, A.; Barker-Collo, S.L.; Baune, B.T.; Béjot, Y.; Belachew, A.B.; Bennett, D.A.; Biadgo, B.; Bijani, A.; Bin Sayeed, M.S.; Brayne, C.; Carpenter, D.O.; Carvalho, F.; Catalá-López, F.; Cerin, E.; Choi, J-Y.J.; Dang, A.K.; Degefa, M.G.; Djalalinia, S.; Dubey, M.; Duken, E.E.; Edvardsson, D.; Endres, M.; Eskandarieh, S.; Faro, A.; Farzadfar, F.; Fereshtehnejad, S-M.; Fernandes, E.; Filip, I.; Fischer, F.; Gebre, A.K.; Geremew, D.; Ghasemi-Kasman, M.; Gnedovskaya, E.V.; Gupta, R.; Hachinski, V.; Hagos, T.B.; Hamidi, S.; Hankey, G.J.; Haro, J.M.; Hay, S.I.; Irvani, S.S.N.; Jha, R.P.; Jonas, J.B.; Kalani, R.; Karch, A.; Kasaeian, A.; Khader, Y.S.; Khalil, I.A.; Khan, E.A.; Khanna, T.; Khoja, T.A.M.; Khubchandani, J.; Kisa, A.; Kissimova-Skarbek, K.; Kivimäki, M.; Koyanagi, A.; Krohn, K.J.; Logroscino, G.; Lorkowski, S.; Majdan, M.; Malekzadeh, R.; März, W.; Massano, J.; Mengistu, G.; Meretoja, A.; Mohammadi, M.; Mohammadi-Khanaposhtani, M.; Mokdad, A.H.; Mondello, S.; Moradi, G.; Nagel, G.; Naghavi, M.; Naik, G.; Nguyen, L.H.; Nguyen, T.H.; Nirayo, Y.L.; Nixon, M.R.; Ofori-Asenso, R.; Ogbo, F.A.; Olagunju, A.T.; Owolabi, M.O.; Panda-Jonas, S.; Passos, V.M.A.; Pereira, D.M.; Pinilla-Monsalve, G.D.; Piradov, M.A.; Pond, C.D.; Poustchi, H.; Qorbani, M.; Radfar, A.; Reiner, R.C., Jr; Robinson, S.R.; Roshandel, G.; Rostami, A.; Russ, T.C.; Sachdev, P.S.; Safari, H.; Safiri, S.; Sahathevan, R.; Salimi, Y.; Satpathy, M.; Sawhney, M.; Saylan, M.; Sepanlou, S.G.; Shafieesabet, A.; Shaikh, M.A.; Sahraian, M.A.; Shigematsu, M.; Shiri, R.; Shiue, I.; Silva, J.P.; Smith, M.; Sobhani, S.; Stein, D.J.; Tabarés-Seisdedos, R.; Tovani-Palone, M.R.; Tran, B.X.; Tran, T.T.; Tsegay, A.T.; Ullah, I.; Venketasubramanian, N.; Vlassov, V.; Wang, Y-P.; Weiss, J.; Westerman, R.; Wijeratne, T.; Wyper, G.M.A.; Yano, Y.; Yimer, E.M.; Yonemoto, N.; Yousefifard, M.; Zaidi, Z.; Zare, Z.; Vos, T.; Feigin, V.L.; Murray, C.J.L. Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol., 2019, 18(1), 88-106.
[http://dx.doi.org/10.1016/S1474-4422(18)30403-4] [PMID: 30497964]
[5]
Park, J. Mortality from Alzheimer’s disease in Canada: A multiple-cause-of-death analysis, 2004 to 2011. Public Health Rep., 2016, 27(5), 17-21.
[PMID: 27192207]
[6]
Sharma, K. Cholinesterase inhibitors as Alzheimer’s therapeutics. Mol. Med. Rep., 2019, 20(2), 1479-1487.
[PMID: 31257471]
[7]
Ahmad, M. Donepezil: A review of the recent structural modifications and their impact on anti-Alzheimer activity. Braz. J. Pharm. Sci., 2020, 56, 1-13.
[8]
Vaz, M.; Silva, V.; Monteiro, C.; Silvestre, S. Role of aducanumab in the treatment of Alzheimer’s Disease: Challenges and opportunities. Clin. Interv. Aging, 2022, 17, 797-810.
[http://dx.doi.org/10.2147/CIA.S325026] [PMID: 35611326]
[9]
Lipton, S.A.; Nicotera, P. Calcium, free radicals and excitotoxins in neuronal apoptosis. Cell Calcium, 1998, 23(2-3), 165-171.
[http://dx.doi.org/10.1016/S0143-4160(98)90115-4] [PMID: 9601612]
[10]
Fish, P.V.; Steadman, D.; Bayle, E.D.; Whiting, P. New approaches for the treatment of Alzheimer’s disease. Bioorg. Med. Chem. Lett., 2019, 29(2), 125-133.
[http://dx.doi.org/10.1016/j.bmcl.2018.11.034] [PMID: 30501965]
[11]
Hassan, N.A.; Alshamari, A.K.; Hassan, A.A.; Elharrif, M.G.; Alhajri, A.M.; Sattam, M.; Khattab, R.R. Advances on therapeutic strategies for Alzheimer’s Disease: From medicinal plant to nanotechnology. Molecules, 2022, 27(15), 4839.
[http://dx.doi.org/10.3390/molecules27154839] [PMID: 35956796]
[12]
Wallis, R.S.; Jakubiec, W.; Kumar, V.; Bedarida, G.; Silvia, A.; Paige, D.; Zhu, T.; Mitton-Fry, M.; Ladutko, L.; Campbell, S.; Miller, P.F. Biomarker-assisted dose selection for safety and efficacy in early development of PNU-100480 for tuberculosis. Antimicrob. Agents Chemother., 2011, 55(2), 567-574.
[http://dx.doi.org/10.1128/AAC.01179-10] [PMID: 21078950]
[13]
Kerru, N.; Gummidi, L.; Maddila, S.; Gangu, K.K.; Jonnalagadda, S.B. A review on recent advances in nitrogen-containing molecules and their biological applications. Molecules, 2020, 25(8), 1909.
[http://dx.doi.org/10.3390/molecules25081909] [PMID: 32326131]
[14]
Ghai, R.; Nagarajan, K.; Arora, M.; Grover, P.; Ali, N.; Kapoor, G. Current strategies and novel drug approaches for Alzheimer disease. CNS Neurol. Disord. Drug Targets, 2020, 19, 676-690.
[http://dx.doi.org/10.2174/1871527319666200717091513]
[15]
Aggarwal, H.; Gupta, S.; Sharma, P.; Sharma, B.M.; Sharma, B. Neurobehavioral and neurobiochemical effect of atomoxetine and N-acetylcysteine in streptozotocin diabetes induced endothelial dysfunction and related dementia. Physiol. Behav., 2022, 249, 113767.
[http://dx.doi.org/10.1016/j.physbeh.2022.113767]
[16]
Bari, A.; Iqbal, A.; Khan, Z.A.; Shahzad, S.A.; Yar, M. Synthetic approaches toward piperidine related structures: A review. Synth. Commun., 2020, 50(17), 2572-2589.
[http://dx.doi.org/10.1080/00397911.2020.1776878]
[17]
Rk, M.; BEGUM, S.; BEGUM, A. Antioxidant potential of piperidine containing compounds-a short review. Atherosclerosis, 2018, 10, 12.
[18]
Kramer, K.J. The surprising re-emergence of droperidol. Anesth. Prog., 2020, 67(3), 125-126.
[http://dx.doi.org/10.2344/anpr-67-03-14] [PMID: 32992339]
[19]
Thom, R.P.; Mock, C.K.; Teslyar, P. Delirium in hospitalized patients: Risks and benefits of antipsychotics. Cleve. Clin. J. Med., 2017, 84(8), 616-622.
[http://dx.doi.org/10.3949/ccjm.84a.16077] [PMID: 28806160]
[20]
Grözinger, M.; Dragicevic, A.; Hiemke, C.; Shams, M.; Müller, M.J.; Härtter, S. Melperone is an inhibitor of the CYP2D6 catalyzed O-demethylation of venlafaxine. Pharmacopsychiatry, 2003, 36(1), 3-6.
[http://dx.doi.org/10.1055/s-2003-38084] [PMID: 12649767]
[21]
Christian, R.; Saavedra, L.; Gaynes, B.N.; Sheitman, B.; Wines, R.C.M.; Jonas, D.E.; Viswanathan, M.; Ellis, A.R.; Woodell, C.; Carey, T.S. Future Research Needs for First- and SecondGeneration Antipsychotics for Children and Young Adults; Agency for Healthcare Research and Quality (US): Rockville (MD), 2012.
[22]
Haas, M.; Delbello, M.P.; Pandina, G.; Kushner, S.; Van Hove, I.; Augustyns, I.; Quiroz, J.; Kusumakar, V. Risperidone for the treatment of acute mania in children and adolescents with bipolar disorder: A randomized, double-blind, placebo-controlled study. Bipolar Disord., 2009, 11(7), 687-700.
[http://dx.doi.org/10.1111/j.1399-5618.2009.00750.x] [PMID: 19839994]
[23]
Cheng, H-W.; Liang, Y-H.; Kuo, Y-L.; Chuu, C-P.; Lin, C-Y.; Lee, M-H.; Wu, A.T.H.; Yeh, C-T.; Chen, E.I-T.; Whang-Peng, J.; Su, C-L.; Huang, C-Y.F. Identification of thioridazine, an antipsychotic drug, as an antiglioblastoma and anticancer stem cell agent using public gene expression data. Cell Death Dis., 2015, 6(5), e1753.
[http://dx.doi.org/10.1038/cddis.2015.77] [PMID: 25950483]
[24]
Manu, N.; Schilling, M.W.; Phillips, T.W. Natural and synthetic repellents for pest management of the storage mite Tyrophagus putrescentiae (Schrank) (Sarcoptiformes: Acaridae). Insects, 2021, 12(8), 711.
[http://dx.doi.org/10.3390/insects12080711] [PMID: 34442277]
[25]
Loi, B.; Sahai, M.A.; De Luca, M.A.; Shiref, H.; Opacka-Juffry, J. The role of dopamine in the stimulant characteristics of novel psychoactive substances (NPS)—Neurobiological and computational assessment using the case of desoxypipradrol (2-DPMP). Front. Pharmacol., 2020, 11, 806.
[http://dx.doi.org/10.3389/fphar.2020.00806] [PMID: 32670057]
[26]
D’Amelio, P.; Isaia, G.C. The use of raloxifene in osteoporosis treatment. Expert Opin. Pharmacother., 2013, 14(7), 949-956.
[http://dx.doi.org/10.1517/14656566.2013.782002] [PMID: 23521229]
[27]
McLaughlin, V.V.; Rich, S. Pulmonary hypertension. Curr. Probl. Cardiol., 2004, 29(10), 575-634.
[http://dx.doi.org/10.1016/S0146-2806(04)00149-5] [PMID: 15494704]
[28]
Stanley, T.H. The fentanyl story. J. Pain, 2014, 15(12), 1215-1226.
[http://dx.doi.org/10.1016/j.jpain.2014.08.010] [PMID: 25441689]
[29]
Zhou, Y.; Sridhar, R.; Shan, L.; Sha, W.; Gu, X.; Sukumar, S. Loperamide, an FDA-approved antidiarrhea drug, effectively reverses the resistance of multidrug resistant MCF-7/MDR1 human breast cancer cells to doxorubicin-induced cytotoxicity. Cancer Invest., 2012, 30(2), 119-125.
[http://dx.doi.org/10.3109/07357907.2011.640653] [PMID: 22250587]
[30]
Barenholtz, H.A.; McLeod, D.C. Loratadine: A nonsedating antihistamine with once-daily dosing. DICP, 1989, 23(6), 445-450.
[http://dx.doi.org/10.1177/106002808902300601] [PMID: 2525847]
[31]
Pae, C.U.; Patkar, A.A. Paroxetine: Current status in psychiatry. Expert Rev. Neurother., 2007, 7(2), 107-120.
[http://dx.doi.org/10.1586/14737175.7.2.107] [PMID: 17286545]
[32]
Schmitt, F.; Hussain, G.; Dupuis, L.; Loeffler, J.P.; Henriques, A. A plural role for lipids in motor neuron diseases: Energy, signaling and structure. Front. Cell. Neurosci., 2014, 8, 25.
[http://dx.doi.org/10.3389/fncel.2014.00025] [PMID: 24600344]
[33]
Kovacs, G.G. Current concepts of neurodegerative diseases. Cit EMJ Neurol., 2014, 1, 78-86.
[34]
Van Assche, R.; Temmerman, L.; Dias, D.A.; Boughton, B.; Boonen, K.; Braeckman, B.P.; Schoofs, L.; Roessner, U. Metabolic profiling of a transgenic Caenorhabditis elegans Alzheimer model. Metabolomics, 2015, 11(2), 477-486.
[http://dx.doi.org/10.1007/s11306-014-0711-5] [PMID: 25750603]
[35]
Hussain, G.; Shahzad, A.; Anwar, H.; Mahmood Baig, S.; Shabbir, A.; De Aaguilar, J.L.G. Neurological disorder burden in faisalabad, punjab-pakistan: Data from the major tertiary carecenters of the city. Pakistan J Neurol Sci., 2017, 12(3), 3-10.
[36]
Cai, Z.; Wang, C.; Yang, W. Role of berberine in Alzheimer’s disease. Neuropsychiatr. Dis. Treat., 2016, 12, 2509-2520.
[http://dx.doi.org/10.2147/NDT.S114846] [PMID: 27757035]
[37]
Kwon, J.; Seo, Y.H.; Lee, J.E.; Seo, E.K.; Li, S.; Guo, Y.; Hong, S.B.; Park, S.Y.; Lee, D. Spiroindole alkaloids and spiroditerpenoids from Aspergillus duricaulis and their potential neuroprotective effects. J. Nat. Prod., 2015, 78(11), 2572-2579.
[http://dx.doi.org/10.1021/acs.jnatprod.5b00508] [PMID: 26517152]
[38]
Nhan, H.S.; Chiang, K.; Koo, E.H. The multifaceted nature of amyloid precursor protein and its proteolytic fragments: Friends and foes. Acta Neuropathol., 2015, 129(1), 1-19.
[http://dx.doi.org/10.1007/s00401-014-1347-2] [PMID: 25287911]
[39]
Baranello, R.J.; Bharani, K.L.; Padmaraju, V.; Chopra, N.; Lahiri, D.K.; Greig, N.H.; Pappolla, M.A.; Sambamurti, K. Amyloid-beta protein clearance and degradation (ABCD) pathways and their role in Alzheimer’s disease. Curr. Alzheimer Res., 2015, 12(1), 32-46.
[http://dx.doi.org/10.2174/1567205012666141218140953] [PMID: 25523424]
[40]
Kamagata, K.; Tomiyama, H.; Hatano, T.; Motoi, Y.; Abe, O.; Shimoji, K.; Kamiya, K.; Suzuki, M.; Hori, M.; Yoshida, M.; Hattori, N.; Aoki, S. A preliminary diffusional kurtosis imaging study of Parkinson disease: Comparison with conventional diffusion tensor imaging. Neuroradiology, 2014, 56(3), 251-258.
[http://dx.doi.org/10.1007/s00234-014-1327-1] [PMID: 24468858]
[41]
Schrag, A.; Horsfall, L.; Walters, K.; Noyce, A.; Petersen, I. Prediagnostic presentations of Parkinson’s disease in primary care: A case-control study. Lancet Neurol., 2015, 14(1), 57-64.
[http://dx.doi.org/10.1016/S1474-4422(14)70287-X] [PMID: 25435387]
[42]
Palfi, S.; Gurruchaga, J.M.; Ralph, G.S.; Lepetit, H.; Lavisse, S.; Buttery, P.C.; Watts, C.; Miskin, J.; Kelleher, M.; Deeley, S.; Iwamuro, H.; Lefaucheur, J.P.; Thiriez, C.; Fenelon, G.; Lucas, C.; Brugières, P.; Gabriel, I.; Abhay, K.; Drouot, X.; Tani, N.; Kas, A.; Ghaleh, B.; Le Corvoisier, P.; Dolphin, P.; Breen, D.P.; Mason, S.; Guzman, N.V.; Mazarakis, N.D.; Radcliffe, P.A.; Harrop, R.; Kingsman, S.M.; Rascol, O.; Naylor, S.; Barker, R.A.; Hantraye, P.; Remy, P.; Cesaro, P.; Mitrophanous, K.A. Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson’s disease: A dose escalation, open-label, phase 1/2 trial. Lancet, 2014, 383(9923), 1138-1146.
[http://dx.doi.org/10.1016/S0140-6736(13)61939-X] [PMID: 24412048]
[43]
McNamara, C.G.; Tejero-Cantero, Á.; Trouche, S.; Campo-Urriza, N.; Dupret, D. Dopaminergic neurons promote hippocampal reactivation and spatial memory persistence. Nat. Neurosci., 2014, 17(12), 1658-1660.
[http://dx.doi.org/10.1038/nn.3843] [PMID: 25326690]
[44]
Recasens, A.; Dehay, B. Alpha-synuclein spreading in Parkinson’s disease. Front. Neuroanat., 2014, 8, 159.
[http://dx.doi.org/10.3389/fnana.2014.00159] [PMID: 25565982]
[45]
Schapira, A.H.V.; Olanow, C.W.; Greenamyre, J.T.; Bezard, E. Slowing of neurodegeneration in Parkinson’s disease and Huntington’s disease: Future therapeutic perspectives. Lancet, 2014, 384(9942), 545-555.
[http://dx.doi.org/10.1016/S0140-6736(14)61010-2] [PMID: 24954676]
[46]
Wang, Y.; Reis, C.; Applegate, R, II.; Stier, G.; Martin, R.; Zhang, J.H. Ischemic conditioning-induced endogenous brain protection: Applications pre-, per- or post-stroke. Exp. Neurol., 2015, 272, 26-40.
[http://dx.doi.org/10.1016/j.expneurol.2015.04.009] [PMID: 25900056]
[47]
Adilijiang, A.; Guan, T.; He, J.; Hartle, K.; Wang, W.; Li, X. The protective effects of areca catechu extract on cognition and social interaction deficits in a cuprizone-induced demyelination model. Evid. Based Complement. Alternat. Med., 2015, 2015, 426092.
[http://dx.doi.org/10.1155/2015/426092] [PMID: 25815032]
[48]
Rački, V.; Petrić, D.; Kučić, N.; Gržeta, N.; Jurdana, K.; Rončević-Gržeta, I. Cortical gray matter loss in schizophrenia: Could microglia be the culprit? Med. Hypotheses, 2016, 88, 18-21.
[http://dx.doi.org/10.1016/j.mehy.2015.12.021] [PMID: 26880628]
[49]
Snyder, M.A.; Gao, W.J. NMDA hypofunction as a convergence point for progression and symptoms of schizophrenia. Front. Cell. Neurosci., 2013, 7, 31.
[http://dx.doi.org/10.3389/fncel.2013.00031] [PMID: 23543703]
[50]
Choudhury, B.; Saytode, P.; Shah, V. Neurodegenrative disorders: Past, present and future. Int. J. Appl. Pharm. Biotechnol., 2014, 5, 14-28.
[51]
Jin, Y.; Khadka, D.B.; Cho, W.J. Pharmacological effects of berberine and its derivatives: A patent update. Expert Opin. Ther. Pat., 2016, 26(2), 229-243.
[http://dx.doi.org/10.1517/13543776.2016.1118060] [PMID: 26610159]
[52]
Jiang, W.; Li, S.; Li, X. Therapeutic potential of berberine against neurodegenerative diseases. Sci. China Life Sci., 2015, 58(6), 564-569.
[http://dx.doi.org/10.1007/s11427-015-4829-0] [PMID: 25749423]
[53]
Jiang, W.; Wei, W.; Gaertig, M.A.; Li, S.; Li, X.J. Therapeutic effect of berberine on Huntington’s disease transgenic mouse model. PLoS One, 2015, 10(7), e0134142.
[http://dx.doi.org/10.1371/journal.pone.0134142] [PMID: 26225560]
[54]
Patil, S.; Tawari, S.; Mundhada, D.; Nadeem, S. Protective effect of berberine, an isoquinoline alkaloid ameliorates ethanol-induced oxidative stress and memory dysfunction in rats. Pharmacol. Biochem. Behav., 2015, 136, 13-20.
[http://dx.doi.org/10.1016/j.pbb.2015.07.001] [PMID: 26159088]
[55]
Dimatelis, J.J.; Russell, V.A.; Stein, D.J.; Daniels, W.M. The effects of lobeline and naltrexone on methamphetamine-induced place preference and striatal dopamine and serotonin levels in adolescent rats with a history of maternal separation. Metab. Brain Dis., 2012, 27(3), 351-361.
[http://dx.doi.org/10.1007/s11011-012-9288-8] [PMID: 22392627]
[56]
Li, C.Y.; Zhao, L.M.; Shi, X.W.; Zhang, J.D. Lobeline shows protective effects against MPTP-induced dopaminergic neuron death and attenuates behavior deficits in animals. Exp. Ther. Med., 2014, 7(2), 375-378.
[http://dx.doi.org/10.3892/etm.2013.1413] [PMID: 24396408]
[57]
Mishra, A.; Punia, J.K.; Bladen, C.; Zamponi, G.W.; Goel, R.K. Anticonvulsant mechanisms of piperine, a piperidine alkaloid. Channels, 2015, 9(5), 317-323.
[http://dx.doi.org/10.1080/19336950.2015.1092836] [PMID: 26542628]
[58]
Hritcu, L.; Noumedem, J.A.; Cioanca, O.; Hancianu, M.; Kuete, V.; Mihasan, M. Methanolic extract of Piper nigrum fruits improves memory impairment by decreasing brain oxidative stress in amyloid beta(1-42) rat model of Alzheimer’s disease. Cell. Mol. Neurobiol., 2014, 34(3), 437-449.
[http://dx.doi.org/10.1007/s10571-014-0028-y] [PMID: 24442916]
[59]
Al-Baghdadi, O.B.; Prater, N.I.; Van der Schyf, C.J.; Geldenhuys, W.J. Inhibition of monoamine oxidase by derivatives of piperine, an alkaloid from the pepper plant Piper nigrum, for possible use in Parkinson’s disease. Bioorg. Med. Chem. Lett., 2012, 22(23), 7183-7188.
[http://dx.doi.org/10.1016/j.bmcl.2012.09.056] [PMID: 23102654]
[60]
Dall’Acqua, S. Plant-derived acetylcholinesterase inhibitory alkaloids for the treatment of Alzheimer’s disease. Botanics, 2013, 3, 19-28.
[http://dx.doi.org/10.2147/BTAT.S17297]
[61]
Tundis, R.; Menichini, F.; Conforti, F.; Loizzo, M.R.; Bonesi, M.; Statti, G.; Menichini, F. A potential role of alkaloid extracts from Salsola species (Chenopodiaceae) in the treatment of Alzheimer’s disease. J. Enzyme Inhib. Med. Chem., 2009, 24(3), 818-824.
[http://dx.doi.org/10.1080/14756360802399662] [PMID: 18720188]
[62]
Orhan, I.E.; Kucukboyaci, N.; Calis, I.; Cerón-Carrasco, J.P.; den-Haan, H.; Peña-García, J.; Pérez-Sánchez, H. Acetylcholinesterase inhibitory assessment of isolated constituents from Salsola grandis Freitag, Vural & Adıgüzel and molecular modeling studies on N -acetyltryptophan. Phytochem. Lett., 2017, 20, 373-378.
[http://dx.doi.org/10.1016/j.phytol.2016.10.017]
[63]
Ribeiro, R.A.; Leite, J.R. Nantenine alkaloid presents anticonvulsant effect on two classical animal models. Phytomedicine, 2003, 10(6-7), 563-568.
[http://dx.doi.org/10.1078/094471103322331557] [PMID: 13678244]
[64]
Xiao, F.; Yan, B.; Chen, L.; Zhou, D. Review of the use of botanicals for epilepsy in complementary medical systems-Traditional Chinese Medicine. Epilepsy Behav., 2015, 52(Pt B), 281-289.
[http://dx.doi.org/10.1016/j.yebeh.2015.04.050] [PMID: 26052078]
[65]
Lima, J.A.; Costa, T.W.R.; Silva, L.L.; Miranda, A.L.P.; Pinto, A.C. Antinociceptive and anti-inflammatory effects of a Geissospermum vellosii stem bark fraction. An. Acad. Bras. Cienc., 2016, 88(1), 237-248.
[http://dx.doi.org/10.1590/0001-3765201520140374] [PMID: 26840005]
[66]
Sajkowska-Kozielewicz, J.J.; Kozielewicz, P.; Barnes, N.M.; Wawer, I.; Paradowska, K. Antioxidant, cytotoxic, and antiproliferative activities and total polyphenol contents of the extracts of Geissospermum reticulatum bark. Oxid. Med. Cell. Longev., 2016, 2016, 2573580.
[http://dx.doi.org/10.1155/2016/2573580] [PMID: 27446507]
[67]
Reina, M.; Ruiz-Mesia, W.; López-Rodríguez, M.; Ruiz-Mesia, L.; González-Coloma, A.; Martínez-Díaz, R. Indole alkaloids from Geissospermum reticulatum. J. Nat. Prod., 2012, 75(5), 928-934.
[http://dx.doi.org/10.1021/np300067m] [PMID: 22551062]
[68]
Vital, M.J.S.; Carneiro, A.L.B.; Silva, L.F.R.; Amorim, R.C.D.N.; Camargo, M.R.M.; Pohlit, A.M. Chemical composition, ethnopharmacology and biological activity of Geissospermum Allemão species (Apocynaceae Juss.). Rev Fitos Eletrônica., 2015, 8, 137-146.
[69]
Araújo, J.Q.; Lima, J.A.; Pinto, Ada.C.; de Alencastro, R.B.; Albuquerque, M.G. Docking of the alkaloid geissospermine into acetylcholinesterase: A natural scaffold targeting the treatment of Alzheimer’s disease. J. Mol. Model., 2011, 17(6), 1401-1412.
[http://dx.doi.org/10.1007/s00894-010-0841-2] [PMID: 20844909]
[70]
Faggion, S.A.; Cunha, A.O.S.; Fachim, H.A.; Gavin, A.S.; dos Santos, W.F.; Pereira, A.M.S.; Beleboni, R.O. Anticonvulsant profile of the alkaloids (+)-erythravine and (+)-11-α-hydroxy-erythravine isolated from the flowers of Erythrina mulungu Mart ex Benth (Leguminosae-Papilionaceae). Epilepsy Behav., 2011, 20(3), 441-446.
[http://dx.doi.org/10.1016/j.yebeh.2010.12.037] [PMID: 21277832]
[71]
Setti-Perdigão, P.; Serrano, M.A.R.; Flausino, O.A., Jr; Bolzani, V.S.; Guimarães, M.Z.P.; Castro, N.G. Erythrina mulungu alkaloids are potent inhibitors of neuronal nicotinic receptor currents in mammalian cells. PLoS One, 2013, 8(12), e82726.
[http://dx.doi.org/10.1371/journal.pone.0082726] [PMID: 24349349]
[72]
Vasconcelos, S.M.M.; Sales, G.T.M.; Lima, N.; Lobato, R.F.G.; Macêdo, D.S.; Barbosa-Filho, J.M.; Leal, L.K.A.M.; Fonteles, M.M.F.; Sousa, F.C.F.; Oliveira, J.L.; Viana, G.S.B. Anti-inflammatory activities of the hydroalcoholic extracts from Erythrina velutina and E. mulungu in mice. Rev. Bras. Farmacogn., 2011, 21(6), 1155-1158.
[http://dx.doi.org/10.1590/S0102-695X2011005000134]
[73]
Wang, H.; Zhang, K.; Zhao, L.; Tang, J.; Gao, L.; Wei, Z. Anti-inflammatory effects of vinpocetine on the functional expression of nuclear factor-kappa B and tumor necrosis factor-alpha in a rat model of cerebral ischemia-reperfusion injury. Neurosci. Lett., 2014, 566, 247-251.
[http://dx.doi.org/10.1016/j.neulet.2014.02.045] [PMID: 24598438]
[74]
Zhang, F.; Yan, C.; Wei, C.; Yao, Y.; Ma, X.; Gong, Z.; Liu, S.; Zang, D.; Chen, J.; Shi, F.D.; Hao, J. Vinpocetine inhibits NF-κB-dependent inflammation in acute ischemic stroke patients. Transl. Stroke Res., 2018, 9(2), 174-184.
[http://dx.doi.org/10.1007/s12975-017-0549-z] [PMID: 28691141]
[75]
Avula, B.; Chittiboyina, A.G.; Sagi, S.; Wang, Y.H.; Wang, M.; Khan, I.A.; Cohen, P.A. Identification and quantification of vinpocetine and picamilon in dietary supplements sold in the United States. Drug Test. Anal., 2016, 8(3-4), 334-343.
[http://dx.doi.org/10.1002/dta.1853] [PMID: 26426301]
[76]
Ruiz-Miyazawa, K.W.; Zarpelon, A.C.; Pinho-Ribeiro, F.A.; Pavão-de-Souza, G.F.; Casagrande, R.; Verri, W.A., Jr Vinpocetine reduces carrageenan-induced inflammatory hyperalgesia in mice by inhibiting oxidative stress, cytokine production and NF-κB activation in the paw and spinal cord. PLoS One, 2015, 10(3), e0118942.
[http://dx.doi.org/10.1371/journal.pone.0118942] [PMID: 25822523]
[77]
Jincai, W.; Tingfang, D.; Yongheng, Z.; Zhongmin, L.; Kaihua, Z.; Xiaohong, L. Effects of vinpocetine and ozagrel on behavioral recovery of rats after global brain ischemia. J. Clin. Neurosci., 2014, 21(4), 661-663.
[http://dx.doi.org/10.1016/j.jocn.2013.07.039] [PMID: 24291485]
[78]
Macedo Vaz, S.; de Freitas Silva, M.; Dos Reis Rosa Franco, G.; Jorge, R.; Guimarães, M.; Motta R da Silva, F.; Gonçalves Castro, N.; Alvim Guedes, I.; Dardenne, L.E.; Amaral Alves, M.; Garrett da Costa, R.; Beserra Pinheiro, G.; Germino Veras, L.; Renata Mortari, M.; Pruccoli, L.; Tarozzi, A.; Viegas, C., Jr Synthesis and biological evaluation of 4-hydroxy-methylpiperidinyl-N-benzyl-acylarylhydrazone hybrids designed as novel multifunctional drug candidates for Alzheimer’s disease. Bioorg. Med. Chem., 2022, 71, 116952.
[http://dx.doi.org/10.1016/j.bmc.2022.116952] [PMID: 35930852]
[79]
Ahmed, A.; Akhtar, S.; Mushtaq, N.; Haider, S.; Munawar, R.; Siddique, H.A.; Akram, A.; Saify, Z.S.; Arif, M. 1,3-di-4-piperidylpropane derivatives as potential acetyl cholinesterase antagonists: Molecular docking, synthesis, and biological evaluation. Pak. J. Pharm. Sci., 2021, 34(3), 855-860.
[PMID: 34602406]
[80]
Lecoutey, C.; Legay, R.; Davis, A.; Sopková-de Oliveira Santos, J.; Dallemagne, P.; Rochais, C. Development of novel potential pleiotropic compounds of interest in alzheimer’s disease treatment through rigidification strategy. Molecules, 2021, 26(9), 2536.
[http://dx.doi.org/10.3390/molecules26092536] [PMID: 33926141]
[81]
Ortiz, C.J.C.; Damasio, C.M.; Pruccoli, L.; Nadur, N.F.; de Azevedo, L.L.; Guedes, I.A.; Dardenne, L.E.; Kümmerle, A.E.; Tarozzi, A.; Viegas, C., Jr Cinnamoyl-N-acylhydrazone-donepezil hybrids: synthesis and evaluation of novel multifunctional ligands against neurodegenerative diseases. Neurochem. Res., 2020, 45(12), 3003-3020.
[http://dx.doi.org/10.1007/s11064-020-03148-2] [PMID: 33079324]
[82]
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]
[83]
Poeschl, A.; Mountford, D.M.; Hider, R.C.; Cilibrizzi, A. Synthetic approaches for piperidone-based templates as scaffolds to access chirally enriched donepezil analogues. ACS Omega, 2020, 5(5), 2378-2396.
[http://dx.doi.org/10.1021/acsomega.9b03808] [PMID: 32064399]
[84]
Celik, I.; Erol, M.; Temiz Arpaci, O.; Sezer Senol, F.; Erdogan Orhan, I. Evaluation of activity of some 2, 5-disubstituted benzoxazole derivatives against acetylcholinesterase, butyrylcholinesterase and tyrosinase: ADME prediction, DFT and comparative molecular docking studies. Polycycl. Aromat. Compd., 2022, 42(2), 412-423.
[http://dx.doi.org/10.1080/10406638.2020.1737827]
[85]
Chaves, S.; Resta, S.; Rinaldo, F.; Costa, M.; Josselin, R.; Gwizdala, K.; Piemontese, L.; Capriati, V.; Pereira-Santos, A.R.; Cardoso, S.M.; Santos, M.A. Design, synthesis, and in vitro evaluation of hydroxybenzimidazole-donepezil analogues as multitarget-directed ligands for the treatment of Alzheimer’s disease. Molecules, 2020, 25(4), 985.
[http://dx.doi.org/10.3390/molecules25040985] [PMID: 32098407]
[86]
Maramai, S.; Benchekroun, M.; Gabr, M.T.; Yahiaoui, S. Multitarget therapeutic strategies for Alzheimer’s disease: Review on emerging target combinations. Bio. Med. Res. Int., 2020, 2020, 5120230.
[http://dx.doi.org/10.1155/2020/5120230] [PMID: 32714977]
[87]
Lalut, J.; Payan, H.; Davis, A.; Lecoutey, C.; Legay, R.; Sopkova-de Oliveira Santos, J.; Claeysen, S.; Dallemagne, P.; Rochais, C. Rational design of novel benzisoxazole derivatives with acetylcholinesterase inhibitory and serotoninergic 5-HT4 receptors activities for the treatment of Alzheimer’s disease. Sci. Rep., 2020, 10(1), 3014.
[http://dx.doi.org/10.1038/s41598-020-59805-7] [PMID: 32080261]
[88]
Saeedi, M.; Felegari, P.; Iraji, A.; Hariri, R.; Rastegari, A.; Mirfazli, S.S.; Edraki, N.; Firuzi, O.; Mahdavi, M.; Akbarzadeh, T. Novel N-benzylpiperidine derivatives of 5-arylisoxazole-3-carboxamides as anti-Alzheimer’s agents. Arch. Pharm., 2021, 354(3), e2000258.
[http://dx.doi.org/10.1002/ardp.202000258] [PMID: 33226157]
[89]
Sharma, P.; Tripathi, A.; Tripathi, P.N.; Prajapati, S.K.; Seth, A.; Tripathi, M.K.; Srivastava, P.; Tiwari, V.; Krishnamurthy, S.; Shrivastava, S.K. Design and development of multitarget-directed N-Benzylpiperidine analogs as potential candidates for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2019, 167, 510-524.
[http://dx.doi.org/10.1016/j.ejmech.2019.02.030] [PMID: 30784883]
[90]
Wang, D.; Hu, M.; Li, X.; Zhang, D.; Chen, C.; Fu, J.; Shao, S.; Shi, G.; Zhou, Y.; Wu, S.; Zhang, T. Design, synthesis, and evaluation of isoflavone analogs as multifunctional agents for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2019, 168, 207-220.
[http://dx.doi.org/10.1016/j.ejmech.2019.02.053] [PMID: 30822710]
[91]
Pourshojaei, Y.; Abiri, A.; Eskandari, K.; Haghighijoo, Z.; Edraki, N.; Asadipour, A. Phenoxyethyl piperidine/Morpholine Derivatives as pAS and cAS inhibitors of cholinesterases: Insights for future Drug Design. Sci. Rep., 2019, 9(1), 19855.
[http://dx.doi.org/10.1038/s41598-019-56463-2] [PMID: 31882733]
[92]
Lanthier, C.; Payan, H.; Liparulo, I.; Hatat, B.; Lecoutey, C.; Since, M.; Davis, A.; Bergamini, C.; Claeysen, S.; Dallemagne, P.; Bolognesi, M.L.; Rochais, C. Novel multi target-directed ligands targeting 5-HT4 receptors with in cellulo antioxidant properties as promising leads in Alzheimer’s disease. Eur. J. Med. Chem., 2019, 182, 111596.
[http://dx.doi.org/10.1016/j.ejmech.2019.111596] [PMID: 31419776]
[93]
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]
[94]
Bajda, M.; Łażewska, D.; Godyń, J.; Zaręba, P.; Kuder, K.; Hagenow, S.; Łątka, K.; Stawarska, E.; Stark, H.; Kieć-Kononowicz, K.; Malawska, B. Search for new multi-target compounds against Alzheimer’s disease among histamine H3 receptor ligands. Eur. J. Med. Chem., 2020, 185, 111785.
[http://dx.doi.org/10.1016/j.ejmech.2019.111785] [PMID: 31669851]
[95]
Andreev, S.; Pantsar, T.; Ansideri, F.; Kudolo, M.; Forster, M.; Schollmeyer, D.; Laufer, S.A.; Koch, P. Design, synthesis and biological evaluation of 7-Chloro-9 H-pyrimido [4, 5-b] indole-based glycogen synthase kinase-3β inhibitors. Molecules, 2019, 24(12), 2331.
[http://dx.doi.org/10.3390/molecules24122331] [PMID: 31242571]
[96]
van Greunen, D.G.; Johan van der Westhuizen, C.; Cordier, W.; Nell, M.; Stander, A.; Steenkamp, V.; Panayides, J.L.; Riley, D.L. Novel N-benzylpiperidine carboxamide derivatives as potential cholinesterase inhibitors for the treatment of Alzheimer’s disease. Eur. J. Med. Chem., 2019, 179, 680-693.
[http://dx.doi.org/10.1016/j.ejmech.2019.06.088] [PMID: 31280020]
[97]
Asadi, M.; Ebrahimi, M.; Mohammadi-Khanaposhtani, M.; Azizian, H.; Sepehri, S.; Nadri, H.; Biglar, M.; Amanlou, M.; Larijani, B.; Mirzazadeh, R.; Edraki, N.; Mahdavi, M. Design, synthesis, molecular docking, and cholinesterase inhibitory potential of phthalimide‐dithiocarbamate hybrids as new agents for treatment of alzheimer’s disease. Chem. Biodivers., 2019, 16(11), e1900370.
[http://dx.doi.org/10.1002/cbdv.201900370] [PMID: 31523926]
[98]
Hussein, W.; Sağlık, B.N.; Levent, S.; Korkut, B.; Ilgın, S.; Özkay, Y.; Kaplancıklı, Z.A. Synthesis and biological evaluation of new cholinesterase inhibitors for Alzheimer’s disease. Molecules, 2018, 23(8), 2033.
[http://dx.doi.org/10.3390/molecules23082033] [PMID: 30110946]
[99]
Singla, S.; Piplani, P. Coumarin derivatives as potential inhibitors of acetylcholinesterase: Synthesis, molecular docking and biological studies. Bioorg. Med. Chem., 2016, 24(19), 4587-4599.
[http://dx.doi.org/10.1016/j.bmc.2016.07.061] [PMID: 27519464]
[100]
Kang, L.; Gao, X.H.; Liu, H.R.; Men, X.; Wu, H.N.; Cui, P.W.; Oldfield, E.; Yan, J.Y. Structure-activity relationship investigation of coumarin-chalcone hybrids with diverse side-chains as acetylcholinesterase and butyrylcholinesterase inhibitors. Mol. Divers., 2018, 22(4), 893-906.
[http://dx.doi.org/10.1007/s11030-018-9839-y] [PMID: 29934672]
[101]
Pachón-Angona, I.; Refouvelet, B.; Andrýs, R.; Martin, H.; Luzet, V.; Iriepa, I.; Moraleda, I.; Diez-Iriepa, D.; Oset-Gasque, M.J.; Marco-Contelles, J.; Musilek, K.; Ismaili, L. Donepezil+chromone+melatonin hybrids as promising agents for Alzheimer’s disease therapy. J. Enzyme Inhib. Med. Chem., 2019, 34(1), 479-489.
[http://dx.doi.org/10.1080/14756366.2018.1545766] [PMID: 30712420]
[102]
Rampa, A.; Bartolini, M.; Pruccoli, L.; Naldi, M.; Iriepa, I.; Moraleda, I.; Belluti, F.; Gobbi, S.; Tarozzi, A.; Bisi, A.; Bisi, A. Exploiting the chalcone scaffold to develop multifunctional agents for Alzheimer’s disease. Molecules, 2018, 23(8), 1902.
[http://dx.doi.org/10.3390/molecules23081902] [PMID: 30061534]
[103]
Dias Viegas, F.P.; de Freitas Silva, M.; Divino da Rocha, M.; Castelli, M.R.; Riquiel, M.M.; Machado, R.P.; Vaz, S.M.; Simões de Lima, L.M.; Mancini, K.C.; Marques de Oliveira, P.C.; Morais, É.P.; Gontijo, V.S.; da Silva, F.M.R.; D’Alincourt da Fonseca Peçanha, D.; Castro, N.G.; Neves, G.A.; Giusti-Paiva, A.; Vilela, F.C.; Orlandi, L.; Camps, I.; Veloso, M.P.; Leomil Coelho, L.F.; Ionta, M.; Ferreira-Silva, G.Á.; Pereira, R.M.; Dardenne, L.E.; Guedes, I.A.; de Oliveira Carneiro, Junior, W.; Quaglio Bellozi, P.M.; Pinheiro de Oliveira, A.C.; Ferreira, F.F.; Pruccoli, L.; Tarozzi, A.; Viegas, C., Jr Design, synthesis and pharmacological evaluation of N-benzyl-piperidinyl-aryl-acylhydrazone derivatives as donepezil hybrids: Discovery of novel multi-target anti-alzheimer prototype drug candidates. Eur. J. Med. Chem., 2018, 147, 48-65.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.066] [PMID: 29421570]
[104]
Menéndez, C.A.; Biscussi, B.; Accordino, S.; Paula Murray, A.; Gerbino, D.C.; Appignanesi, G.A. Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase. Bioorg. Chem., 2017, 75, 201-209.
[http://dx.doi.org/10.1016/j.bioorg.2017.09.012] [PMID: 28963904]
[105]
Basiri, A.; Abd Razik, B.M.; Ezzat, M.O.; Kia, Y.; Kumar, R.S.; Almansour, A.I.; Arumugam, N.; Murugaiyah, V. Synthesis and cholinesterase inhibitory activity study of new piperidone grafted spiropyrrolidines. Bioorg. Chem., 2017, 75, 210-216.
[http://dx.doi.org/10.1016/j.bioorg.2017.09.019] [PMID: 28987876]
[106]
Zhou, L.Y.; Zhu, Y.; Jiang, Y.R.; Zhao, X.J.; Guo, D. Design, synthesis and biological evaluation of dual acetylcholinesterase and phosphodiesterase 5A inhibitors in treatment for Alzheimer’s disease. Bioorg. Med. Chem. Lett., 2017, 27(17), 4180-4184.
[http://dx.doi.org/10.1016/j.bmcl.2017.07.013] [PMID: 28751142]