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Mini-Reviews in Medicinal Chemistry

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ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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Review Article

Calcium Modulating Effect of Polycyclic Cages: A Suitable Therapeutic Approach Against Excitotoxic-induced Neurodegeneration

Author(s): Ayodeji O. Egunlusi, Sarel F. Malan, Vitalii A. Palchykov and Jacques Joubert*

Volume 24, Issue 13, 2024

Published on: 24 January, 2024

Page: [1277 - 1292] Pages: 16

DOI: 10.2174/0113895575273868231128104121

Price: $65

Abstract

Neurodegenerative disorders pose a significant challenge to global healthcare systems due to their progressive nature and the resulting loss of neuronal cells and functions. Excitotoxicity, characterized by calcium overload, plays a critical role in the pathophysiology of these disorders. In this review article, we explore the involvement of calcium dysregulation in neurodegeneration and neurodegenerative disorders. A promising therapeutic strategy to counter calcium dysregulation involves the use of calcium modulators, particularly polycyclic cage compounds. These compounds, structurally related to amantadine and memantine, exhibit neuroprotective properties by attenuating calcium influx into neuronal cells. Notably, the pentacycloundecylamine NGP1-01, a cage-like structure, has shown efficacy in inhibiting both N-methyl-D-aspartate (NMDA) receptors and voltage- gated calcium channels (VGCCs), making it a potential candidate for neuroprotection against excitotoxic-induced neurodegenerative disorders. The structure-activity relationship of polycyclic cage compounds is discussed in detail, highlighting their calcium-inhibitory activities. Various closed, open, and rearranged cage compounds have demonstrated inhibitory effects on calcium influx through NMDA receptors and VGCCs. Additionally, these compounds have exhibited neuroprotective properties, including free radical scavenging, attenuation of neurotoxicities, and reduction of neuroinflammation. Although the calcium modulatory activities of polycyclic cage compounds have been extensively studied, apart from amantadine and memantine, none have undergone clinical trials. Further in vitro and in vivo studies and subsequent clinical trials are required to establish the efficacy and safety of these compounds. The development of polycyclic cages as potential multifunctional agents for treating complex neurodegenerative diseases holds great promise.

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[1]
Breyer, A.; Elstner, M.; Gillessen, T.; Weiser, D.; Elstner, E. Glutamate-induced cell death in neuronal HT22 cells is attenuated by extracts from St. John’s wort (Hypericum perforatum L.). Phytomedicine, 2007, 14(4), 250-255.
[http://dx.doi.org/10.1016/j.phymed.2007.02.001] [PMID: 17346956]
[2]
Shinoda, Y.; Nakajima, Y.; Iguchi, H.; Tatsumi, S.; Kitaoka, M.; Nakajima, M.; Takahashi, T.; Fujiwara, Y.; Furuichi, T. Galacto-Nbiose is neuroprotective against glutamate-induced excitotoxicity in vitro. Eur. J. Pharmacol., 2016, 791, 711-717.
[http://dx.doi.org/10.1016/j.ejphar.2016.10.010] [PMID: 27729249]
[3]
Boussicault, L.; Kacher, R.; Lamazière, A.; Vanhoutte, P.; Caboche, J.; Betuing, S.; Potier, M.C. CYP46A1 protects against NMDA-mediated excitotoxicity in Huntington’s disease: Analysis of lipid raft content. Biochimie, 2018, 153, 70-79.
[http://dx.doi.org/10.1016/j.biochi.2018.07.019] [PMID: 30107216]
[4]
Arundine, M.; Tymianski, M. Molecular mechanisms of calciumdependent neurodegeneration in excitotoxicity. Cell Cal., 2003, 34(4-5), 325-337.
[http://dx.doi.org/10.1016/S0143-4160(03)00141-6] [PMID: 12909079]
[5]
Lai, T.W.; Zhang, S.; Wang, Y.T. Excitotoxicity and stroke: Identifying novel targets for neuroprotection. Prog. Neurobiol., 2014, 115(C), 157-188.
[http://dx.doi.org/10.1016/j.pneurobio.2013.11.006] [PMID: 24361499]
[6]
Liu, W.; Jiang, X.; Zu, Y.; Yang, Y.; Liu, Y.; Sun, X.; Xu, Z.; Ding, H.; Zhao, Q. A comprehensive description of GluN2Bselective N-methyl-D-aspartate (NMDA) receptor antagonists. Eur. J. Med. Chem., 2020, 200, 112447.
[http://dx.doi.org/10.1016/j.ejmech.2020.112447] [PMID: 32450321]
[7]
Egunlusi, A.O. Novel norbornane derivatives as potential neuroprotective agents. 2020. Available from: http://hdl.handle.net/11394/733
[8]
Bano, D.; Ankarcrona, M. Beyond the critical point: An overview of excitotoxicity, calcium overload and the downstream consequences. Neurosci. Lett., 2018, 663(663), 79-85.
[http://dx.doi.org/10.1016/j.neulet.2017.08.048] [PMID: 28843346]
[9]
Yang, E.J.; Park, G.H.; Song, K.S. Neuroprotective effects of liquiritigenin isolated from licorice roots on glutamate-induced apoptosis in hippocampal neuronal cells. Neurotoxicology, 2013, 39, 114-123.
[http://dx.doi.org/10.1016/j.neuro.2013.08.012] [PMID: 24012889]
[10]
Gold, M.; Koczulla, A.R.; Mengel, D.; Koepke, J.; Dodel, R.; Dontcheva, G.; Habib, P.; Bach, J.P. Reduction of glutamateinduced excitotoxicity in murine primary neurons involving calpain inhibition. J. Neurol. Sci., 2015, 359(1-2), 356-362.
[http://dx.doi.org/10.1016/j.jns.2015.11.016] [PMID: 26671142]
[11]
Xu, D.; Chen, H.; Mak, S.; Hu, S.; Tsim, K.W.K.; Hu, Y.; Sun, Y.; Zhang, G.; Wang, Y.; Zhang, Z.; Han, Y. Neuroprotection against glutamate-induced excitotoxicity and induction of neurite outgrowth by T-006, a novel multifunctional derivative of tetramethylpyrazine in neuronal cell models. Neurochem. Int., 2016, 99, 194-205.
[http://dx.doi.org/10.1016/j.neuint.2016.07.006] [PMID: 27445088]
[12]
Jeong, I.; Yang, J.S.; Hong, Y.J.; Kim, H.J.; Hahn, S.J.; Yoon, S.H. Dapoxetine induces neuroprotective effects against glutamate-induced neuronal cell death by inhibiting calcium signaling and mitochondrial depolarization in cultured rat hippocampal neurons. Eur. J. Pharmacol., 2017, 805(805), 36-45.
[http://dx.doi.org/10.1016/j.ejphar.2017.03.033] [PMID: 28322832]
[13]
Mattson, M.P. Excitotoxicity.Stress: Physiology, Biochemistry, and Pathology: Handbook of Stress Series; Fink, G., Ed.; Elsevier Science B.V: Australia, 2019, 3, 125-134.
[http://dx.doi.org/10.1016/B978-0-12-813146-6.00011-4]
[14]
Rivero-Segura, N.A.; Coronado-Mares, M.I.; Rincón-Heredia, R.; Pérez-Torres, I.; Montiel, T.; Pavón, N.; Cabrera-Reyes, E.A.; Massieu, L.; Cerbón, M. Prolactin prevents mitochondrial dysfunction induced by glutamate excitotoxicity in hippocampal neurons. Neurosci. Lett., 2019, 701, 58-64.
[http://dx.doi.org/10.1016/j.neulet.2019.02.027] [PMID: 30790645]
[15]
Zádori, D.; Klivényi, P.; Szalárdy, L.; Fülöp, F.; Toldi, J.; Vécsei, L. Mitochondrial disturbances, excitotoxicity, neuroinflammation and kynurenines: Novel therapeutic strategies for neurodegenerative disorders. J. Neurol. Sci., 2012, 322(1-2), 187-191.
[http://dx.doi.org/10.1016/j.jns.2012.06.004] [PMID: 22749004]
[16]
Jing, G.; Grammatopoulos, T.; Ferguson, P.; Schelman, W.; Weyhenmeyer, J. Inhibitory effects of angiotensin on NMDAinduced cytotoxicity in primary neuronal cultures. Brain Res. Bull., 2004, 62(5), 397-403.
[http://dx.doi.org/10.1016/j.brainresbull.2003.10.011] [PMID: 15168905]
[17]
Kostic, M.; Zivkovic, N.; Cvetanovic, A.; Stojanovic, I.; Colic, M. IL-17 signalling in astrocytes promotes glutamate excitotoxicity: Indications for the link between inflammatory and neurodegenerative events in multiple sclerosis. Mult. Scler. Relat. Disord., 2017, 11(11), 12-17.
[http://dx.doi.org/10.1016/j.msard.2016.11.006] [PMID: 28104249]
[18]
Aepkers, M.; Wünsch, B. Structure–affinity relationship studies of non-competitive NMDA receptor antagonists derived from dexoxadrol and etoxadrol. Bioorg. Med. Chem., 2005, 13(24), 6836-6849.
[http://dx.doi.org/10.1016/j.bmc.2005.07.030] [PMID: 16169732]
[19]
Wanka, L.; Iqbal, K.; Schreiner, P.R. The lipophilic bullet hits the targets: Medicinal chemistry of adamantane derivatives. Chem. Rev., 2013, 113(5), 3516-3604.
[http://dx.doi.org/10.1021/cr100264t] [PMID: 23432396]
[20]
Duque, M.D.; Camps, P.; Profire, L.; Montaner, S.; Vázquez, S.; Sureda, F.X.; Mallol, J.; López-Querol, M.; Naesens, L.; Clercq, E.D.; Radhika Prathalingam, S.; Kelly, J.M. Synthesis and pharmacological evaluation of (2-oxaadamant-1-yl)amines. Bioorg. Med. Chem., 2009, 17(8), 3198-3206.
[http://dx.doi.org/10.1016/j.bmc.2009.02.007] [PMID: 19251424]
[21]
Geldenhuys, W.J.; Terre’Blanche, G.; Van der Schyf, C.J.; Malan, S.F. Screening of novel pentacyclo-undecylamines for neuroprotective activity. Eur. J. Pharmacol., 2003, 458(1-2), 73-79.
[http://dx.doi.org/10.1016/S0014-2999(02)02701-2] [PMID: 12498909]
[22]
Geldenhuys, W.J.; Malan, S.F.; Murugesan, T.; Van der Schyf, C.J.; Bloomquist, J.R. Synthesis and biological evaluation of pentacyclo[5.4.0.02,6.03,10.05,9]undecane derivatives as potential therapeutic agents in Parkinson’s disease. Bioorg. Med. Chem., 2004, 12(7), 1799-1806.
[http://dx.doi.org/10.1016/j.bmc.2003.12.045] [PMID: 15028270]
[23]
Mdzinarishvili, A.; Geldenhuys, W.J.; Abbruscato, T.J.; Bickel, U.; Klein, J.; Schyf, C.J.V. NGP1-01, a lipophilic polycyclic cage amine, is neuroprotective in focal ischemia. Neurosci. Lett., 2005, 383(1-2), 49-53.
[http://dx.doi.org/10.1016/j.neulet.2005.03.042] [PMID: 15936510]
[24]
Hao, J.; Mdzinarishvili, A.; Abbruscato, T.J.; Klein, J.; Geldenhuys, W.J.; Van der Schyf, C.J.; Bickel, U. Neuroprotection in mice by NGP1-01 after transient focal brain ischemia. Brain Res., 2008, 1196, 113-120.
[http://dx.doi.org/10.1016/j.brainres.2007.11.075] [PMID: 18234166]
[25]
Lockman, J.A.; Geldenhuys, W.J.; Jones-Higgins, M.R.; Patrick, J.D.; Allen, D.D.; Van der Schyf, C.J. NGP1-01, a multi-targeted polycyclic cage amine, attenuates brain endothelial cell death in iron overload conditions. Brain Res., 2012, 1489, 133-139.
[http://dx.doi.org/10.1016/j.brainres.2012.10.029] [PMID: 23099055]
[26]
Grobler, E.; Grobler, A.; Van der Schyf, C.J.; Malan, S.F. Effect of polycyclic cage amines on the transmembrane potential of neuronal cells. Bioorg. Med. Chem., 2006, 14(4), 1176-1181.
[http://dx.doi.org/10.1016/j.bmc.2005.09.042] [PMID: 16249094]
[27]
Schyf, C.J.; Geldenhuys, W.J. Polycyclic compounds: Ideal drug scaffolds for the design of multiple mechanism drugs? Neurotherapeutics, 2009, 6(1), 175-186.
[http://dx.doi.org/10.1016/j.nurt.2008.10.037] [PMID: 19110208]
[28]
Kelani, M.T.; Kruger, H.G.; Govender, T.; Maguire, G.E.M.; Naicker, T.; Onajole, O.K. Serendipitous discovery of new pentacycloundecane molecules. J. Mol. Struct., 2020, 1204, 127497.
[http://dx.doi.org/10.1016/j.molstruc.2019.127497]
[29]
Abeti, R.; Abramov, A.Y. Mitochondrial Ca2+ in neurodegenerative disorders. Pharmacol. Res., 2015, 99, 377-381.
[http://dx.doi.org/10.1016/j.phrs.2015.05.007] [PMID: 26013908]
[30]
Pchitskaya, E.; Popugaeva, E.; Bezprozvanny, I. Calcium signaling and molecular mechanisms underlying neurodegenerative diseases. Cell Calcium, 2018, 70, 87-94.
[http://dx.doi.org/10.1016/j.ceca.2017.06.008] [PMID: 28728834]
[31]
Moraes, B.J.; Coelho, P.; Fão, L.; Ferreira, I.L.; Rego, A.C. Modified glutamatergic postsynapse in neurodegenerative disorders. Neuroscience, 2021, 454, 116-139.
[http://dx.doi.org/10.1016/j.neuroscience.2019.12.002] [PMID: 31887357]
[32]
Mazibuko, Z.; Choonara, Y.E.; Kumar, P.; Du Toit, L.C.; Modi, G.; Naidoo, D.; Pillay, V. A review of the potential role of nanoenabled drug delivery technologies in amyotrophic lateral sclerosis: Lessons learned from other neurodegenerative disorders. J. Pharm. Sci., 2015, 104(4), 1213-1229.
[http://dx.doi.org/10.1002/jps.24322] [PMID: 25559087]
[33]
Luo, Y.; Wang, Q.; Zhang, Y. A systems pharmacology approach to decipher the mechanism of danggui-shaoyao-san decoction for the treatment of neurodegenerative diseases. J. Ethnopharmacol., 2016, 178, 66-81.
[http://dx.doi.org/10.1016/j.jep.2015.12.011] [PMID: 26680587]
[34]
Procaccini, C.; Santopaolo, M.; Faicchia, D.; Colamatteo, A.; Formisano, L.; de Candia, P.; Galgani, M.; De Rosa, V.; Matarese, G. Role of metabolism in neurodegenerative disorders. Metabolism, 2016, 65(9), 1376-1390.
[http://dx.doi.org/10.1016/j.metabol.2016.05.018] [PMID: 27506744]
[35]
Ahmad, K.; Baig, M.H.; Gupta, G.K.; Kamal, M.A.; Pathak, N.; Choi, I. Identification of common therapeutic targets for selected neurodegenerative disorders: An in silico approach. J. Comput. Sci., 2016, 17, 292-306.
[http://dx.doi.org/10.1016/j.jocs.2016.03.007]
[36]
Hernández, A.F.; González-Alzaga, B.; López-Flores, I.; Lacasaña, M. Systematic reviews on neurodevelopmental and neurodegenerative disorders linked to pesticide exposure: Methodological features and impact on risk assessment. Environ. Int., 2016, 92-93, 657-679.
[http://dx.doi.org/10.1016/j.envint.2016.01.020] [PMID: 26896854]
[37]
Heusinkveld, H.J.; Wahle, T.; Campbell, A.; Westerink, R.H.S.; Tran, L.; Johnston, H.; Stone, V.; Cassee, F.R.; Schins, R.P.F. Neurodegenerative and neurological disorders by small inhaled particles. Neurotoxicology, 2016, 56, 94-106.
[http://dx.doi.org/10.1016/j.neuro.2016.07.007] [PMID: 27448464]
[38]
Saeedi Saravi, S.S.; Dehpour, A.R. Potential role of organochlorine pesticides in the pathogenesis of neurodevelopmental, neurodegenerative, and neurobehavioral disorders: A review. Life Sci., 2016, 145, 255-264.
[http://dx.doi.org/10.1016/j.lfs.2015.11.006] [PMID: 26549647]
[39]
Leist, M.; Nicotera, P. Apoptosis, excitotoxicity, and neuropathology. Exp. Cell Res., 1998, 239(2), 183-201.
[http://dx.doi.org/10.1006/excr.1997.4026] [PMID: 9521837]
[40]
Moreira, P.I.; Zhu, X.; Wang, X.; Lee, H.; Nunomura, A.; Petersen, R.B.; Perry, G.; Smith, M.A. Mitochondria: A therapeutic target in neurodegeneration. Biochim. Biophys. Acta Mol. Basis Dis., 2010, 1802(1), 212-220.
[http://dx.doi.org/10.1016/j.bbadis.2009.10.007] [PMID: 19853657]
[41]
Celsi, F.; Pizzo, P.; Brini, M.; Leo, S.; Fotino, C.; Pinton, P.; Rizzuto, R. Mitochondria, calcium and cell death: A deadly triad in neurodegeneration. Biochim. Biophys. Acta Bioenerg., 2009, 1787(5), 335-344.
[http://dx.doi.org/10.1016/j.bbabio.2009.02.021] [PMID: 19268425]
[42]
Mehta, A.; Prabhakar, M.; Kumar, P.; Deshmukh, R.; Sharma, P.L. Excitotoxicity: Bridge to various triggers in neurodegenerative disorders. Eur. J. Pharmacol., 2013, 698(1-3), 6-18.
[http://dx.doi.org/10.1016/j.ejphar.2012.10.032] [PMID: 23123057]
[43]
Yacoubian, T.A. Neurodegenerative Disorders: Why Do We Need New Therapies?Drug Discovery Approaches for the Treatment of Neurodegenerative Disorders: Alzheimer’s Disease; Adejare, A., Ed.; Elsevier Science B.V.: Amsterdam, 2017, pp. 1-16.
[http://dx.doi.org/10.1016/B978-0-12-802810-0.00001-5]
[44]
Qureshi, I.A.; Mehler, M.F. Epigenetic mechanisms governing the process of neurodegeneration. Mol. Aspects Med., 2013, 34(4), 875-882.
[http://dx.doi.org/10.1016/j.mam.2012.06.011] [PMID: 22782013]
[45]
Kumar, M.; John, M.; Madhavan, M.; James, J.; Omkumar, R.V. Alteration in the phosphorylation status of NMDA receptor GluN2B subunit by activation of both NMDA receptor and L-type voltage gated calcium channel. Neurosci. Lett., 2019, 709, 134343.
[http://dx.doi.org/10.1016/j.neulet.2019.134343] [PMID: 31279915]
[46]
Park, H.J.; Kwak, M.; Baek, S.H. Neuroprotective effects of dendropanax morbifera leaves on glutamate-induced oxidative cell death in HT22 mouse hippocampal neuronal cells. J. Ethnopharmacol., 2019, 2020, 251.
[http://dx.doi.org/10.1016/j.jep.2019.112518] [PMID: 31884031]
[47]
Smidkova, M.; Hajek, M.; Adla, S.K.; Slavikova, B.; Chodounska, H.; Matousova, M.; Mertlikova-Kaiserova, H.; Kudova, E. Screening of novel 3α5β-neurosteroids for neuroprotective activity against glutamate or NMDA-induced excitotoxicity. J. Steroid Biochem. Mol. Biol., 2019, 189, 195-203.
[http://dx.doi.org/10.1016/j.jsbmb.2019.03.007] [PMID: 30872014]
[48]
Deschepper, M.; Hoogendoorn, B.; Brooks, S.; Dunnett, S.B.; Jones, L. Proteomic changes in the brains of Huntington’s disease mouse models reflect pathology and implicate mitochondrial changes. Brain Res. Bull., 2012, 88(2-3), 210-222.
[http://dx.doi.org/10.1016/j.brainresbull.2011.01.012] [PMID: 21272615]
[49]
Lee, J.G.; Yon, J.M.; Lin, C.; Jung, A.Y.; Jung, K.Y.; Nam, S.Y. Combined treatment with capsaicin and resveratrol enhances neuroprotection against glutamate-induced toxicity in mouse cerebral cortical neurons. Food Chem. Toxicol., 2012, 50(11), 3877-3885.
[http://dx.doi.org/10.1016/j.fct.2012.08.040] [PMID: 22943972]
[50]
Park, E.; Lee, G.J.; Choi, S.; Choi, S.K.; Chae, S.J.; Kang, S.W.; Park, H.K. Correlation between extracellular glutamate release and neuronal cell death in an eleven vessel occlusion model in rat. Brain Res., 2010, 1342, 160-166.
[http://dx.doi.org/10.1016/j.brainres.2010.04.054] [PMID: 20427014]
[51]
Taveira, M.; Sousa, C.; Valentão, P.; Ferreres, F.; Teixeira, J.P.; Andrade, P.B. Neuroprotective effect of steroidal alkaloids on glutamate-induced toxicity by preserving mitochondrial membrane potential and reducing oxidative stress. J. Steroid Biochem. Mol. Biol., 2014, 140, 106-115.
[http://dx.doi.org/10.1016/j.jsbmb.2013.12.013] [PMID: 24373792]
[52]
Pereira, E.P.L.; Braga-de-Souza, S.; Santos, C.C.; Santos, L.O.; Cerqueira, M.D.; Ribeiro, P.R.; Fernandez, L.G.; Silva, V.D.A.; Costa, S.L. Amburana cearensis seed extracts protect PC-12 cells against toxicity induced by glutamate. Rev. Bras. Farmacogn., 2017, 27(2), 199-205.
[http://dx.doi.org/10.1016/j.bjp.2016.08.010]
[53]
Berntsen, H.F.; Bjørklund, C.G.; Strandabø, R.; Haug, T.M.; Moldes-Anaya, A.; Fuentes-Lazaro, J.; Verhaegen, S.; Paulsen, R.E.; Tasker, R.A.; Ropstad, E. PFOS-induced excitotoxicity is dependent on Ca2+ influx via NMDA receptors in rat cerebellar granule neurons. Toxicol. Appl. Pharmacol., 2018, 357, 19-32.
[http://dx.doi.org/10.1016/j.taap.2018.08.015] [PMID: 30144469]
[54]
Kim, H.N.; Kim, Y.R.; Jang, J.Y.; Choi, Y.W.; Baek, J.U.; Hong, J.W.; Choi, Y.H.; Shin, H.K.; Choi, B.T. Neuroprotective effects of Polygonum multiflorum extract against glutamate-induced oxidative toxicity in HT22 hippocampal cells. J. Ethnopharmacol., 2013, 150(1), 108-115.
[http://dx.doi.org/10.1016/j.jep.2013.08.014] [PMID: 23973786]
[55]
Yang, R.; Cui, H.J.; Wang, H.; Wang, Y.; Liu, J.H.; Li, Y.; Lu, Y. N-stearoyltyrosine protects against glutamate-induced oxidative toxicity by an apoptosis-inducing factor (AIF)-mediated caspase-independent cell death pathway. J. Pharmacol. Sci., 2014, 124(2), 169-179.
[http://dx.doi.org/10.1254/jphs.13184FP] [PMID: 24463778]
[56]
Jazvinšćak Jembrek, M.; Radovanović, V.; Vlainić, J.; Vuković, L.; Hanžić, N. Neuroprotective effect of zolpidem against glutamate-induced toxicity is mediated via the PI3K/Akt pathway and inhibited by PK11195. Toxicology, 2018, 406-407, 58-69.
[http://dx.doi.org/10.1016/j.tox.2018.05.014] [PMID: 29859204]
[57]
Abeysinghe, A.A.D.T.; Deshapriya, R.D.U.S.; Udawatte, C. Alzheimer’s disease; a review of the pathophysiological basis and therapeutic interventions. Life Sci., 2020, 256, 117996.
[http://dx.doi.org/10.1016/j.lfs.2020.117996] [PMID: 32585249]
[58]
Koutsilieri, E.; Riederer, P. Excitotoxicity and new antiglutamatergic strategies in Parkinson’s disease and Alzheimer’s disease. Parkinsonism Relat. Disord., 2007, 13(3), S329-S331.
[http://dx.doi.org/10.1016/S1353-8020(08)70025-7] [PMID: 18267259]
[59]
Tannenberg, R.K.; Dodd, P.R. Cell damage/excitotoxicity | excitotoxicity and neurodegenerative disease. In: In Encyclopedia of Basic Epilepsy Research; Philip, A.; Schwartz, K., Eds.; Elsevier Science B.V: Califonia; , 2009; pp. 114-119.
[http://dx.doi.org/10.1016/B978-012373961-2.00069-2]
[60]
Alberch, J.; Pérez-Navarro, E.; Canals, J.M. Neuroprotection by neurotrophins and GDNF family members in the excitotoxic model of Huntington’s disease. Brain Res. Bull., 2002, 57(6), 817-822.
[http://dx.doi.org/10.1016/S0361-9230(01)00775-4] [PMID: 12031278]
[61]
Giampà, C.; Patassini, S.; Borreca, A.; Laurenti, D.; Marullo, F.; Bernardi, G.; Menniti, F.S.; Fusco, F.R. Phosphodiesterase 10 inhibition reduces striatal excitotoxicity in the quinolinic acid model of Huntington’s disease. Neurobiol. Dis., 2009, 34(3), 450-456.
[http://dx.doi.org/10.1016/j.nbd.2009.02.014] [PMID: 19281846]
[62]
Anitha, M.; Nandhu, M.S.; Anju, T.R.; Jes, P.; Paulose, C.S. Targeting glutamate mediated excitotoxicity in huntington’s disease: Neural progenitors and partial glutamate antagonist. Memantine. Med. Hypotheses, 2011, 76(1), 138-140.
[http://dx.doi.org/10.1016/j.mehy.2010.09.003] [PMID: 20943326]
[63]
Winkler, C.; Gil, J.M.A.C.; Araújo, I.M.; Rieß, O.; Skripuletz, T.; von Hörsten, S.; Petersén, Å. Normal sensitivity to excitotoxicity in a transgenic Huntington’s disease rat. Brain Res. Bull., 2006, 69(3), 306-310.
[http://dx.doi.org/10.1016/j.brainresbull.2006.01.003] [PMID: 16564426]
[64]
Ryu, J.K.; Choi, H.B.; McLarnon, J.G. Combined minocycline plus pyruvate treatment enhances effects of each agent to inhibit inflammation, oxidative damage, and neuronal loss in an excitotoxic animal model of Huntington’s disease. Neuroscience, 2006, 141(4), 1835-1848.
[http://dx.doi.org/10.1016/j.neuroscience.2006.05.043] [PMID: 16809003]
[65]
Fan, M.; Raymond, L. N-Methyl-d-aspartate (NMDA) receptor function and excitotoxicity in Huntington’s disease. Prog. Neurobiol., 2007, 81(5-6), 272-293.
[http://dx.doi.org/10.1016/j.pneurobio.2006.11.003] [PMID: 17188796]
[66]
Estrada Sánchez, A.M.; Mejía-Toiber, J.; Massieu, L. Excitotoxic neuronal death and the pathogenesis of Huntington’s disease. Arch. Med. Res., 2008, 39(3), 265-276.
[http://dx.doi.org/10.1016/j.arcmed.2007.11.011] [PMID: 18279698]
[67]
Henningsen, J.B.; Soylu-Kucharz, R.; Björkqvist, M.; Petersén, Å. Effects of excitotoxicity in the hypothalamus in transgenic mouse models of Huntington disease. Heliyon, 2021, 7(8), e07808.
[http://dx.doi.org/10.1016/j.heliyon.2021.e07808] [PMID: 34458633]
[68]
Fan, J.; Gladding, C.M.; Wang, L.; Zhang, L.Y.J.; Kaufman, A.M.; Milnerwood, A.J.; Raymond, L.A. P38 MAPK is involved in enhanced NMDA receptor-dependent excitotoxicity in YAC transgenic mouse model of Huntington disease. Neurobiol. Dis., 2012, 45(3), 999-1009.
[http://dx.doi.org/10.1016/j.nbd.2011.12.019] [PMID: 22198502]
[69]
Chen, T.; Yang, Y.; Luo, P.; Liu, W.; Dai, S.; Zheng, X.; Fei, Z.; Jiang, X. Homer1 knockdown protects dopamine neurons through regulating calcium homeostasis in an in vitro model of Parkinson’s disease. Cell. Signal., 2013, 25(12), 2863-2870.
[http://dx.doi.org/10.1016/j.cellsig.2013.09.004] [PMID: 24036210]
[70]
Ludtmann, M.H.R.; Abramov, A.Y. Mitochondrial calcium imbalance in Parkinson’s disease. Neurosci. Lett., 2018, 663(663), 86-90.
[http://dx.doi.org/10.1016/j.neulet.2017.08.044] [PMID: 28838811]
[71]
Burbulla, L.F.; Krainc, D. The role of dopamine in the pathogenesis of GBA1-linked Parkinson’s disease. Neurobiol. Dis., 2019, 132, 104545.
[http://dx.doi.org/10.1016/j.nbd.2019.104545] [PMID: 31351996]
[72]
Surmeier, D.J.; Schumacker, P.T.; Guzman, J.D.; Ilijic, E.; Yang, B.; Zampese, E. Biochemical and Biophysical Research Communications Calcium and Parkinson ’ s Disease. Biochem. Biophys. Res. Commun., 2016, 483, 1-7.
[73]
Surmeier, D.J.; Schumacker, P.T. Calcium, bioenergetics, and neuronal vulnerability in Parkinson’s disease. J. Biol. Chem., 2013, 288(15), 10736-10741.
[http://dx.doi.org/10.1074/jbc.R112.410530] [PMID: 23086948]
[74]
Surmeier, D.J.; Halliday, G.M.; Simuni, T. Calcium, mitochondrial dysfunction and slowing the progression of Parkinson’s disease., Exp. Neurol., 2017, 298(Pt B), 202-209.
[http://dx.doi.org/10.1016/j.expneurol.2017.08.001] [PMID: 28780195]
[75]
Phillipson, O.T. Alpha-synuclein, epigenetics, mitochondria, metabolism, calcium traffic, & circadian dysfunction in Parkinson’s disease. An integrated strategy for management. Ageing Res. Rev., 2017, 40, 149-167.
[http://dx.doi.org/10.1016/j.arr.2017.09.006] [PMID: 28986235]
[76]
Meredith, G.E.; Totterdell, S.; Potashkin, J.A.; Surmeier, D.J.; Modeling, P.D. Modeling PD pathogenesis in mice: Advantages of a chronic MPTP protocol. Parkinsonism Relat. Disord., 2008, 14(Suppl. 2), S112-S115.
[http://dx.doi.org/10.1016/j.parkreldis.2008.04.012] [PMID: 18585085]
[77]
Meredith, G.E.; Totterdell, S.; Beales, M.; Meshul, C.K. Impaired glutamate homeostasis and programmed cell death in a chronic MPTP mouse model of Parkinson’s disease. Exp. Neurol., 2009, 219(1), 334-340.
[http://dx.doi.org/10.1016/j.expneurol.2009.06.005] [PMID: 19523952]
[78]
Caudle, W.M.; Zhang, J. Glutamate, excitotoxicity, and programmed cell death in parkinson disease. Exp. Neurol., 2009, 220(2), 230-233.
[http://dx.doi.org/10.1016/j.expneurol.2009.09.027] [PMID: 19815009]
[79]
Dey, K.; Bazala, M.A.; Kuznicki, J. Targeting mitochondrial calcium pathways as a potential treatment against parkinson’s disease. Cell Calcium, 2020, 89, 102216.
[http://dx.doi.org/10.1016/j.ceca.2020.102216]
[80]
Iovino, L.; Tremblay, M.E.; Civiero, L. Glutamate-induced excitotoxicity in Parkinson’s disease: The role of glial cells. J. Pharmacol. Sci., 2020, 144(3), 151-164.
[http://dx.doi.org/10.1016/j.jphs.2020.07.011] [PMID: 32807662]
[81]
Nutini, M.; Frazzini, V.; Marini, C.; Spalloni, A.; Sensi, S.L.; Longone, P. Zinc pre-treatment enhances NMDAR-mediated excitotoxicity in cultured cortical neurons from SOD1G93A mouse, a model of amyotrophic lateral sclerosis. Neuropharmacology, 2011, 60(7-8), 1200-1208.
[http://dx.doi.org/10.1016/j.neuropharm.2010.11.001] [PMID: 21056589]
[82]
Battaglia, G.; Bruno, V. Metabotropic glutamate receptor involvement in the pathophysiology of amyotrophic lateral sclerosis: new potential drug targets for therapeutic applications. Curr. Opin. Pharmacol., 2018, 38, 65-71.
[http://dx.doi.org/10.1016/j.coph.2018.02.007] [PMID: 29529498]
[83]
Van Den Bosch, L.; Van Damme, P.; Bogaert, E.; Robberecht, W. The role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis. Biochim. Biophys. Acta Mol. Basis Dis., 2006, 1762(11-12), 1068-1082.
[http://dx.doi.org/10.1016/j.bbadis.2006.05.002] [PMID: 16806844]
[84]
Taghibiglou, C.; Lu, J.; Mackenzie, I.R.; Wang, Y.T.; Cashman, N.R. Sterol regulatory element binding protein-1 (SREBP1) activation in motor neurons in excitotoxicity and amyotrophic lateral sclerosis (ALS): Indip, a potential therapeutic peptide. Biochem. Biophys. Res. Commun., 2011, 413(2), 159-163.
[http://dx.doi.org/10.1016/j.bbrc.2011.08.011] [PMID: 21871872]
[85]
Sako, W.; Abe, T.; Izumi, Y.; Harada, M.; Kaji, R. The ratio of N-acetyl aspartate to glutamate correlates with disease duration of amyotrophic lateral sclerosis. J. Clin. Neurosci., 2016, 27(27), 110-113.
[http://dx.doi.org/10.1016/j.jocn.2015.08.044] [PMID: 26765768]
[86]
Lipton, S.A. Failures and successes of NMDA receptor antagonists: Molecular basis for the use of open-channel blockers like memantine in the treatment of acute and chronic neurologic insults. NeuroRx, 2004, 1(1), 101-110.
[http://dx.doi.org/10.1602/neurorx.1.1.101] [PMID: 15717010]
[87]
Sonkusare, S.K.; Kaul, C.L.; Ramarao, P. Dementia of Alzheimer’s disease and other neurodegenerative disorders—memantine, a new hope. Pharmacol. Res., 2005, 51(1), 1-17.
[http://dx.doi.org/10.1016/j.phrs.2004.05.005] [PMID: 15519530]
[88]
Krull, O.; Wünsch, B. Synthesis and structure/NMDA receptor affinity relationships of 1-substituted tetrahydro-3-benzazepines. Bioorg. Med. Chem., 2004, 12(6), 1439-1451.
[http://dx.doi.org/10.1016/j.bmc.2003.12.036] [PMID: 15018917]
[89]
Barygin, O.I.; Gmiro, V.E.; Kim, K.K.; Magazanik, L.G.; Tikhonov, D.B. Blockade of NMDA receptor channels by 9-aminoacridine and its derivatives. Neurosci. Lett., 2009, 451(1), 29-33.
[http://dx.doi.org/10.1016/j.neulet.2008.12.036] [PMID: 19111901]
[90]
Zambrano, P.; Suwalsky, M.; Jemiola-Rzeminska, M.; Strzalka, K. Studies on the interaction of NMDA receptor antagonist memantine with cell membranes: A mini-review. Chem. Biol. Interact., 2018, 283, 47-50.
[http://dx.doi.org/10.1016/j.cbi.2018.01.022] [PMID: 29407462]
[91]
Temme, L.; Bechthold, E.; Schreiber, J.A.; Gawaskar, S.; Schepmann, D.; Robaa, D.; Sippl, W.; Seebohm, G.; Wünsch, B. Negative allosteric modulators of the GluN2B NMDA receptor with phenylethylamine structure embedded in ring-expanded and ring-contracted scaffolds. Eur. J. Med. Chem., 2020, 190, 112138.
[http://dx.doi.org/10.1016/j.ejmech.2020.112138] [PMID: 32070917]
[92]
Costa, B.M.; Irvine, M.W.; Fang, G.; Eaves, R.J.; Mayo-Martin, M.B.; Laube, B.; Jane, D.E.; Monaghan, D.T. Structure-activity relationships for allosteric NMDA receptor inhibitors based on 2-naphthoic acid. Neuropharmacology, 2012, 62(4), 1730-1736.
[http://dx.doi.org/10.1016/j.neuropharm.2011.11.019] [PMID: 22155206]
[93]
Beinat, C.; Banister, S.D.; Hoban, J.; Tsanaktsidis, J.; Metaxas, A.; Windhorst, A.D.; Kassiou, M. Structure–activity relationships of N-substituted 4-(trifluoromethoxy)benzamidines with affinity for GluN2B-containing NMDA receptors. Bioorg. Med. Chem. Lett., 2014, 24(3), 828-830.
[http://dx.doi.org/10.1016/j.bmcl.2013.12.087] [PMID: 24412068]
[94]
Lütnant, I.; Schepmann, D.; Wünsch, B. Benzimidazolone bioisosteres of potent GluN2B selective NMDA receptor antagonists. Eur. J. Med. Chem., 2016, 116, 136-146.
[http://dx.doi.org/10.1016/j.ejmech.2016.03.065] [PMID: 27061977]
[95]
Jiang, S.X.; Zheng, R.Y.; Zeng, J.Q.; Li, X.L.; Han, Z.; Hou, S.T. Reversible inhibition of intracellular calcium influx through NMDA receptors by imidazoline I2 receptor antagonists. Eur. J. Pharmacol., 2010, 629(1-3), 12-19.
[http://dx.doi.org/10.1016/j.ejphar.2009.11.063] [PMID: 19958763]
[96]
Anekonda, T.S.; Quinn, J.F.; Harris, C.; Frahler, K.; Wadsworth, T.L.; Woltjer, R.L. L-type voltage-gated calcium channel blockade with isradipine as a therapeutic strategy for Alzheimer’s disease. Neurobiol. Dis., 2011, 41(1), 62-70.
[http://dx.doi.org/10.1016/j.nbd.2010.08.020] [PMID: 20816785]
[97]
Hurley, M.J.; Dexter, D.T. Voltage-gated calcium channels and Parkinson’s disease. Pharmacol. Ther., 2012, 133(3), 324-333.
[http://dx.doi.org/10.1016/j.pharmthera.2011.11.006] [PMID: 22133841]
[98]
Warnock, A.; Tan, L.; Li, C.; an Haack, K.; Narayan, S.B.; Bennett, M.J. Amlodipine prevents apoptotic cell death by correction of elevated intracellular calcium in a primary neuronal model of Batten disease (CLN3 disease). Biochem. Biophys. Res. Commun., 2013, 436(4), 645-649.
[http://dx.doi.org/10.1016/j.bbrc.2013.04.113] [PMID: 23769828]
[99]
Singh, A.; Verma, P.; Balaji, G.; Samantaray, S.; Mohanakumar, K.P. Nimodipine, an L-type calcium channel blocker attenuates mitochondrial dysfunctions to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinsonism in mice. Neurochem. Int., 2016, 99, 221-232.
[http://dx.doi.org/10.1016/j.neuint.2016.07.003] [PMID: 27395789]
[100]
Calvo-Martín, G.; Plano, D.; Martínez-Sáez, N.; Aydillo, C.; Moreno, E.; Espuelas, S.; Sanmartín, C. Norbornene and related structures as scaffolds in the search for new cancer treatments. Pharmaceuticals, 2022, 15(12), 1465.
[http://dx.doi.org/10.3390/ph15121465] [PMID: 36558915]
[101]
Weller, M.; Finiels-Marlier, F.; Paul, S.M. NMDA receptormediated glutamate toxicity of cultured cerebellar, cortical and mesencephalic neurons: neuroprotective properties of amantadine and memantine. Brain Res., 1993, 613(1), 143-148.
[http://dx.doi.org/10.1016/0006-8993(93)90464-X] [PMID: 8102306]
[102]
Wenk, G.L.; Danysz, W.; Mobley, S.L. MK-801, memantine and amantadine show neuroprotective activity in the nucleus basalis magnocellularis. Eur. J. Pharmacol., 1995, 293(3), 267-270.
[http://dx.doi.org/10.1016/0926-6917(95)00028-3] [PMID: 8666045]
[103]
Chen, H.S.; Wang, Y.F.; Rayudu, P.V.; Edgecomb, P.; Neill, J.C.; Segal, M.M.; Lipton, S.A.; Jensen, F.E. Neuroprotective concentrations of the N-methyl-D-aspartate open-channel blocker memantine are effective without cytoplasmic vacuolation following post-ischemic administration and do not block maze learning or long-term potentiation. Neuroscience, 1998, 86(4), 1121-1132.
[http://dx.doi.org/10.1016/S0306-4522(98)00163-8] [PMID: 9697119]
[104]
Rogawski, M.A.; Wenk, G.L. The neuropharmacological basis for the use of memantine in the treatment of Alzheimer’s disease. CNS Drug Rev., 2003, 9(3), 275-308.
[http://dx.doi.org/10.1111/j.1527-3458.2003.tb00254.x] [PMID: 14530799]
[105]
Kornhuber, J.; Quack, G.; Danysz, W.; Jellinger, K.; Danielczyk, W.; Gsell, W.; Riederer, P. Therapeutic brain concentration of the NMDA receptor antagonist amantadine. Neuropharmacology, 1995, 34(7), 713-721.
[http://dx.doi.org/10.1016/0028-3908(95)00056-C] [PMID: 8532138]
[106]
Duque, M.D.; Camps, P.; Torres, E.; Valverde, E.; Sureda, F.X.; López-Querol, M.; Camins, A.; Prathalingam, S.R.; Kelly, J.M.; Vázquez, S. New oxapolycyclic cage amines with NMDA receptor antagonist and trypanocidal activities. Bioorg. Med. Chem., 2010, 18(1), 46-57.
[http://dx.doi.org/10.1016/j.bmc.2009.11.017] [PMID: 19954985]
[107]
Marotta, G.; Basagni, F.; Rosini, M.; Minarini, A. Memantine derivatives as multitarget agents in alzheimer’s disease. Molecules, 2020, 25(17), 4005.
[http://dx.doi.org/10.3390/molecules25174005] [PMID: 32887400]
[108]
Sklyarova, A.S.; Rodionov, V.N.; Parsons, C.G.; Quack, G.; Schreiner, P.R.; Fokin, A.A. Preparation and testing of homocubyl amines as therapeutic NMDA receptor antagonists. Med. Chem. Res., 2013, 22(1), 360-366.
[http://dx.doi.org/10.1007/s00044-012-0029-7]
[109]
Camps, P.; Duque, M.D.; Vázquez, S.; Naesens, L.; Clercq, E.D.; Sureda, F.X.; López-Querol, M.; Camins, A.; Pallàs, M.; Prathalingam, S.R.; Kelly, J.M.; Romero, V.; Ivorra, D.; Cortés, D. Synthesis and pharmacological evaluation of several ringcontracted amantadine analogs. Bioorg. Med. Chem., 2008, 16(23), 9925-9936.
[http://dx.doi.org/10.1016/j.bmc.2008.10.028] [PMID: 18954995]
[110]
Torres, E.; Duque, M.D.; López-Querol, M.; Taylor, M.C.; Naesens, L.; Ma, C.; Pinto, L.H.; Sureda, F.X.; Kelly, J.M.; Vázquez, S. Synthesis of benzopolycyclic cage amines: NMDA receptor antagonist, trypanocidal and antiviral activities. Bioorg. Med. Chem., 2012, 20(2), 942-948.
[http://dx.doi.org/10.1016/j.bmc.2011.11.050] [PMID: 22178660]
[111]
Valverde, E.; Sureda, F.X.; Vázquez, S. Novel benzopolycyclic amines with NMDA receptor antagonist activity. Bioorg. Med. Chem., 2014, 22(9), 2678-2683.
[http://dx.doi.org/10.1016/j.bmc.2014.03.025] [PMID: 24698811]
[112]
Pérez-Areales, F.J.; Turcu, A.L.; Barniol-Xicota, M.; Pont, C.; Pivetta, D.; Espargaró, A.; Bartolini, M.; De Simone, A.; Andrisano, V.; Pérez, B.; Sabate, R.; Sureda, F.X.; Vázquez, S.; Muñoz-Torrero, D. A novel class of multitarget anti-Alzheimer benzohomoadamantane‒chlorotacrine hybrids modulating cholinesterases and glutamate NMDA receptors. Eur. J. Med. Chem., 2019, 180, 613-626.
[http://dx.doi.org/10.1016/j.ejmech.2019.07.051] [PMID: 31351393]
[113]
Turcu, A.L.; Companys-Alemany, J.; Phillips, M.B.; Patel, D.S.; Griñán-Ferré, C.; Loza, M.I.; Brea, J.M.; Pérez, B.; Soto, D.; Sureda, F.X.; Kurnikova, M.G.; Johnson, J.W.; Pallàs, M.; Vázquez, S. Design, synthesis, and in vitro and in vivo characterization of new memantine analogs for Alzheimer’s disease. Eur. J. Med. Chem., 2022, 236, 114354.
[http://dx.doi.org/10.1016/j.ejmech.2022.114354] [PMID: 35453065]
[114]
Sasaki, T.; Eguchi, S.; Kiriyama, T. A facile synthesis of monooxa- and -aza-bird-cage compounds transannular cyclization. Tetrahedron Lett., 1971, 12(28), 2651-2654.
[http://dx.doi.org/10.1016/S0040-4039(01)96942-4]
[115]
Van der Schyf, C.J.; Squier, G.J.; Coetzee, W.A. Characterization of NGP 1-01, an aromatic polycyclic amine, as a calcium antagonist. Pharmacol. Res. Commun., 1986, 18(5), 407-417.
[http://dx.doi.org/10.1016/0031-6989(86)90162-1] [PMID: 3737654]
[116]
Malan, S.F.; Van der Walt, J.J.; Van der Schyf, C.J. Structureactivity relationships of polycyclic aromatic amines with calcium channel blocking activity. Arch. Pharm., 2000, 333(1), 10-16.
[http://dx.doi.org/10.1002/(SICI)1521-4184(200001)333:1<10:AID-ARDP10>3.0.CO;2-5] [PMID: 10675984]
[117]
Muraki, K.; Watanabe, M.; Imaizumi, Y. Nifedipine and nisoldipine modulate membrane potential of vascular endothelium via a myo-endothelial pathway. Life Sci., 2000, 67(26), 3163-3170.
[http://dx.doi.org/10.1016/S0024-3205(00)00908-5] [PMID: 11191623]
[118]
Bisi, A.; Feoli, A.; Trezza, A.; Viejo, L.; Formaggio, F.; Bartolini, M.; Belluti, F.; Gobbi, S.; Spiga, O.; Caprini, M.; de los Rios, C.; Castellano, S.; Rampa, A. Targeting neuronal calcium channels and GSK3β for Alzheimer’s disease with naturally-inspired Diels-Alder adducts. Bioorg. Chem., 2022, 129, 106152.
[http://dx.doi.org/10.1016/j.bioorg.2022.106152] [PMID: 36155094]
[119]
Young, L.M.; Geldenhuys, W.J.; Domingo, O.C.; Malan, S.F.; Van der Schyf, C.J. Synthesis and biological evaluation of pentacycloundecylamines and triquinylamines as voltage‐gated calcium channel blockers. Arch. Pharm., 2016, 349(4), 252-267.
[http://dx.doi.org/10.1002/ardp.201500293] [PMID: 26892182]
[120]
Malan, S.F.; Dyason, K.; Wagenaar, B.; Jurgens van der Walt, J.; Van der Schyf, C.J. The structure and ion channel activity of 6-benzylamino-3-hydroxyhexacyclo [6.5.0.03,7.04,12.05,10.09,13] Tridecane. Arch. Pharm., 2003, 336(2), 127-133.
[http://dx.doi.org/10.1002/ardp.200390009] [PMID: 12761766]
[121]
Kiewert, C.; Hartmann, J.; Stoll, J.; Thekkumkara, T.J.; Van der Schyf, C.J.; Klein, J. NGP1-01 is a brain-permeable dual blocker of neuronal voltage- and ligand-operated calcium channels. Neurochem. Res., 2006, 31(3), 395-399.
[http://dx.doi.org/10.1007/s11064-005-9036-0] [PMID: 16733815]
[122]
Lemmer, H.J.; Joubert, J.; van Dyk, S.; van der Westhuizen, F.H.; Malan, S.F. S-nitrosylation and attenuation of excessive calcium flux by pentacycloundecane derivatives. Med. Chem., 2012, 8(3), 361-371.
[http://dx.doi.org/10.2174/1573406411208030361] [PMID: 22530904]
[123]
Sharma, R.; Joubert, J.; Malan, S. Synthesis and biological evaluations of NO-Donating Oxa- and aza-pentacycloundecane derivatives as potential neuroprotective candidates. Molecules, 2018, 23(2), 308.
[http://dx.doi.org/10.3390/molecules23020308] [PMID: 29385098]
[124]
Sharma, R.; Joubert, J.; Su, H.; Caira, M.R.; Malan, S.F. Synthesis, crystal structure, DFT studies and biological evaluation of Nbenzamido derivatives of oxahexacycloundecyl amines: A case of enantiomerism leading to molecular disorder. J. Mol. Struct., 2020, 1215, 128248.
[http://dx.doi.org/10.1016/j.molstruc.2020.128248]
[125]
Geldenhuys, W.J.; Malan, S.F.; Bloomquist, J.R.; Van der Schyf, C.J. Structure–activity relationships of pentacycloundecylamines at the N-methyl-d-aspartate receptor. Bioorg. Med. Chem., 2007, 15(3), 1525-1532.
[http://dx.doi.org/10.1016/j.bmc.2006.09.060] [PMID: 17157509]
[126]
Geldenhuys, W.J.; Malan, S.F.; Bloomquist, J.R.; Marchand, A.P.; Van der Schyf, C.J. Pharmacology and structure-activity relationships of bioactive polycyclic cage compounds: A focus on pentacycloundecane derivatives. Med. Res. Rev., 2005, 25(1), 21-48.
[http://dx.doi.org/10.1002/med.20013] [PMID: 15389731]
[127]
Joubert, J.; Dyk, S.; Green, I.R.; Malan, S.F. Synthesis, evaluation and application of polycyclic fluorescent analogues as N-methyl-daspartate receptor and voltage gated calcium channel ligands. Eur. J. Med. Chem., 2011, 46(10), 5010-5020.
[http://dx.doi.org/10.1016/j.ejmech.2011.08.008] [PMID: 21868136]
[128]
Zindo, F.T.; Barber, Q.R.; Joubert, J.; Bergh, J.J.; Petzer, J.P.; Malan, S.F. Polycyclic propargylamine and acetylene derivatives as multifunctional neuroprotective agents. Eur. J. Med. Chem., 2014, 80, 122-134.
[http://dx.doi.org/10.1016/j.ejmech.2014.04.039] [PMID: 24769350]
[129]
Zindo, F.T.; Malan, S.F.; Omoruyi, S.I.; Enogieru, A.B.; Ekpo, O.E.; Joubert, J. Design, synthesis and evaluation of pentacycloundecane and hexacycloundecane propargylamine derivatives as multifunctional neuroprotective agents. Eur. J. Med. Chem., 2019, 163, 83-94.
[http://dx.doi.org/10.1016/j.ejmech.2018.11.051] [PMID: 30503945]
[130]
Egunlusi, A.O.; Malan, S.F.; Omoruyi, S.I.; Ekpo, O.E.; Palchykov, V.A.; Joubert, J. Open and rearranged norbornane derived polycyclic cage molecules as potential neuroprotective agents through attenuation of MPP+- and calcium overload-induced excitotoxicity in neuroblastoma SH-SY5Y cells. Eur. J. Med. Chem., 2020, 204, 112617.
[http://dx.doi.org/10.1016/j.ejmech.2020.112617] [PMID: 32717484]
[131]
Egunlusi, A.O.; Malan, S.F.; Omoruyi, S.I.; Ekpo, O.E.; Joubert, J. 4-Oxatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione Derivatives as NMDA Receptor- and VGCC blockers with neuroprotective potential. Molecules, 2020, 25(19), 4552.
[http://dx.doi.org/10.3390/molecules25194552] [PMID: 33027964]
[132]
Bova, S.; Saponara, S.; Rampa, A.; Gobbi, S.; Cima, L.; Fusi, F.; Sgaragli, G.; Cavalli, M.; de los Rios, C.; Striessnig, J.; Bisi, A. Anthracene based compounds as new L-type Ca2+ channel blockers: Design, synthesis, and full biological profile. J. Med. Chem., 2009, 52(5), 1259-1262.
[http://dx.doi.org/10.1021/jm801589x] [PMID: 19203272]
[133]
Bisi, A.; Arribas, R.L.; Micucci, M.; Budriesi, R.; Feoli, A.; Castellano, S.; Belluti, F.; Gobbi, S.; de los Rios, C.; Rampa, A. Polycyclic maleimide-based derivatives as first dual modulators of neuronal calcium channels and GSK-3β for Alzheimer’s disease treatment. Eur. J. Med. Chem., 2019, 163, 394-402.
[http://dx.doi.org/10.1016/j.ejmech.2018.12.003] [PMID: 30530190]
[134]
Parsons, C.G.; Danysz, W.; Quack, G. Memantine and the aminoalkyl-cyclohexane MRZ 2/579 are moderate affinity uncompetitive NMDA receptor antagonists in vitro characterisation. Amino Acids, 2000, 19(1), 157-166.
[http://dx.doi.org/10.1007/s007260070044] [PMID: 11026484]

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