{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:37:53Z","timestamp":1767832673864,"version":"3.49.0"},"reference-count":166,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,15]],"date-time":"2022-01-15T00:00:00Z","timestamp":1642204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>The incidence of neurodegenerative diseases, such as Alzheimer\u2019s disease (AD), increases continuously demanding the urgent development of anti-Alzheimer\u2019s agents. Marine organisms (MO) have to create their own defenses due to the adverse environment where they live and so synthesize several classes of compounds, such as akaloids, to defend themselves. Therefore, the identification of marine natural products with neuroprotective effects is a necessity. Being that AD is not only a genetic but also an environmental complex disease, a treatment for AD remains to discover. As the major clinical indications (CI) of AD are extracellular plaques formed by \u03b2-amyloid (A\u03b2) protein, intracellular neurofibrillary tangles (NFTs) formed by hyper phosphorylated \u03c4-protein, uncommon inflammatory response and neuron apoptosis and death caused by oxidative stress, alkaloids that may decrease CI, might be used against AD. Most of the alkalolids with those properties are derivatives of the amino acid tryptophan mainly with a planar indole scaffold. Certainly, alkaloids targeting more than one CI, multitarget-directed ligands (MTDL), have the potential to become a lead in AD treatment. Alkaloids to have a maximum of activity against CI, should be planar and contain halogens and amine quaternization.<\/jats:p>","DOI":"10.3390\/md20010075","type":"journal-article","created":{"date-parts":[[2022,1,16]],"date-time":"2022-01-16T20:45:21Z","timestamp":1642365921000},"page":"75","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Marine Organisms as Alkaloid Biosynthesizers of Potential Anti-Alzheimer Agents"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6736-8729","authenticated-orcid":false,"given":"Elisabete","family":"Lima","sequence":"first","affiliation":[{"name":"Faculty of Science and Technology (FCT), Institute of Agricultural and Environmental Research and Technology (IITAA), University of Azores, 9500-321 Ponta Delgada, S\u00e3o Miguel, A\u00e7ores, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8833-5881","authenticated-orcid":false,"given":"Jorge","family":"Medeiros","sequence":"additional","affiliation":[{"name":"Faculty of Science and Technology (FCT), Biotechnology Centre of Azores (CBA), University of Azores, 9500-321 Ponta Delgada, S\u00e3o Miguel, A\u00e7ores, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Russo, P., Kisialiou, A., Lamonaca, P., Moroni, R., Prinzi, G., and Fini, M. (2016). New drugs from marine organisms in Alzheimer\u2019s disease. Mar. Drugs, 14.","DOI":"10.3390\/md14010005"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2019). Alzheimer\u2019s disease facts and figures. Alzheimer\u2019s Dement., 15, 321\u2013387.","DOI":"10.1016\/j.jalz.2019.01.010"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"307","DOI":"10.2147\/CIA.S11718","article-title":"Late onset Alzheimer\u2019s diseasae in older people","volume":"5","author":"Isik","year":"2010","journal-title":"Clin. Interv. Aging"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/gim.2015.117","article-title":"The genetic landscape of Alzheimer disease: Clinical implications and perspectives","volume":"18","author":"Sleegers","year":"2016","journal-title":"Genet. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.plipres.2010.09.001","article-title":"Apolipoprotein E: From lipid transport to neurobiology","volume":"50","author":"Hauser","year":"2011","journal-title":"Prog. Lipid Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrneurol.2012.263","article-title":"Apoliprotein E and Alzheimer disease: Risk, mechanisms and therapy","volume":"9","author":"Liu","year":"2013","journal-title":"Nat. Ver. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.neuron.2009.06.026","article-title":"The role of apoliprotein E in Alzheimer\u2019s disease","volume":"63","author":"Kim","year":"2009","journal-title":"Neuron"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nature24016","article-title":"ApoE\u03b54 markedly exacerbates tau-mediated neurodegeneration in a mouse mode tauopathy","volume":"549","author":"Shi","year":"2017","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1177\/0891988710383571","article-title":"Genetics of Alzheimer\u2019s disease","volume":"23","author":"Bekris","year":"2010","journal-title":"J. Geriatr. Psychiatry Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Martins, M., Silva, R., MM Pinto, M., and Sousa, E. (2020). Marine natural products, multitarget therapy and repurposed agents in Alzheimer\u2019s disease. Pharmaceuticals, 13.","DOI":"10.3390\/ph13090242"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1016\/j.bmc.2011.12.042","article-title":"A review on coumarins as acetylcholinesterase inhibitors for Alzheimer\u2019s disease","volume":"20","author":"Anand","year":"2012","journal-title":"Bioorg. Med. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ebiom.2015.01.002","article-title":"Recent advances from the bench toward the bedside in Alzheimer\u2019s disease","volume":"2","author":"Macauley","year":"2015","journal-title":"EBioMedicine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"665","DOI":"10.2174\/156720510793611600","article-title":"Tau aggregation is a therapeutic target for Alzheimer\u2019s disease","volume":"7","author":"Takashima","year":"2010","journal-title":"Curr. Alzheimer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.ijge.2016.07.003","article-title":"New therapeutic targets in Alzheimer\u2019s disease","volume":"11","author":"Coman","year":"2017","journal-title":"Int. J. Gerontol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"779","DOI":"10.3233\/JAD-180766","article-title":"Treatment combinatoirs for Alzheimer\u2019s disease: Current and future pharmacotherapy options","volume":"67","author":"Cummings","year":"2019","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.bmcl.2018.11.034","article-title":"New approaches for the treatment of Alzheimer\u2019s disease","volume":"29","author":"Fish","year":"2019","journal-title":"Bioorgan. Med. Chem. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1146\/annurev.cellbio.13.1.83","article-title":"Microtubule polymerization dynamics","volume":"13","author":"Desai","year":"1997","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1038\/312237a0","article-title":"Dynamic instability of microtubule growth","volume":"312","author":"Mitchison","year":"1984","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8979","DOI":"10.1021\/jm301079z","article-title":"Microtubule stabilizing agents as potential treatment for Alzheimer\u2019s disease and related neurodegenerative tauopathies","volume":"55","author":"Ballatore","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"White, J.A., Banerjee, R., and Gunawardena, S. (2016). Axonal transport and neurodegeneration: How marine drugs can be used for the development of therapeutics. Mar. Drugs, 14.","DOI":"10.3390\/md14050102"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"4044","DOI":"10.1073\/pnas.83.11.4044","article-title":"Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease","volume":"83","author":"Kosik","year":"1986","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","first-page":"151979","article-title":"Tau hyperphosphorylation and oxidative stress, a critical vicious circle in neurodegenerative tauopathies?","volume":"2015","author":"Naini","year":"2015","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/731526","article-title":"Structure and pathology of tau protein in Alzheimer disease","volume":"2012","author":"Kolarova","year":"2012","journal-title":"Int. J. Alzheimers Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/j.arr.2012.06.003","article-title":"Tau protein kinases: Involvement in Alzheimer\u2019s disease","volume":"12","author":"Martin","year":"2013","journal-title":"Ageing Res. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nrd2896","article-title":"Alzheimer\u2019s disease: Strategies for disease modification","volume":"9","author":"Citron","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"15938","DOI":"10.1074\/jbc.M314116200","article-title":"Casein kinase 1 delta phosphorylates tau and disrupts its binding to microtubules","volume":"279","author":"Li","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Llorach-Pares, L., Nonell-Canals, A., Avila, C., and Sanchez-Martinez, M. (2018). Kororamides, convolutamines, and \u00edndole derivatives as possible tau and dual-specifity kinase inhibitors for Alzheimer\u2019s disease: A computational study. Mar. Drugs, 16.","DOI":"10.3390\/md16100386"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"539","DOI":"10.2174\/1389450115666140226112321","article-title":"Human CDC2-Like Kinase 1 (CLK1): A Novel Target for Alzheimer\u2019s Disease","volume":"15","author":"Jain","year":"2014","journal-title":"Curr. Drug Targets"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"189","DOI":"10.3389\/fncel.2013.00189","article-title":"Recent developments of protein kinase inhibitors as potential AD therapeutics","volume":"7","author":"Tell","year":"2013","journal-title":"Front. Cell Neurosci."},{"key":"ref_30","first-page":"595","article-title":"The role of tau kinases in Alzheimer\u2019s disease","volume":"13","author":"Dolan","year":"2010","journal-title":"Curr. Opin. Drug Discov. Devel."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"681","DOI":"10.4155\/fmc-2016-0013","article-title":"DYRKlA inhibition as potential treatment for Alzheimer\u2019s disease","volume":"8","author":"Stotani","year":"2016","journal-title":"Future Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1111\/acel.12648","article-title":"Dyrkl inhibition improves Alzheimer\u2019s disease-like pathology","volume":"16","author":"Branca","year":"2017","journal-title":"Aging Cell"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1111\/j.1471-4159.2007.05194.x","article-title":"The GSK3 hypothesis of Alzheimer\u2019s disease","volume":"104","author":"Hooper","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_34","first-page":"46","article-title":"GSK-3, a pivotal kinase in Alzheimer disease","volume":"7","author":"Jurado","year":"2014","journal-title":"Front. Mol. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.expneurol.2009.09.011","article-title":"GSK3: A possible link between beta amyloid peptide and tau protein","volume":"223","author":"Lucas","year":"2010","journal-title":"Exp. Neurol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S141","DOI":"10.3233\/JAD-2012-129025","article-title":"GSK3 and tau: Two convergence points in Alzheimer\u2019s disease","volume":"33","author":"Hemandez","year":"2012","journal-title":"J. Alzheimers Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nri3705","article-title":"Innate immune activation in neurodegenerative disease","volume":"14","author":"Heneka","year":"2014","journal-title":"Nat. Rev. lmmunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s11910-017-0733-2","article-title":"Neuroinflammation in neurodegenerative disorders\u2014A review","volume":"17","author":"Schain","year":"2017","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Barbalace, M.C., Malaguti, M., Giusti, L., Lucacchini, A., Hrelia, S., and Angeloni, C. (2019). Anti-inflammatory activities of marine algae in neurodegenerative diseases. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20123061"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1038\/nm.4397","article-title":"Microglia emerge as central players in brain disease","volume":"23","author":"Salter","year":"2017","journal-title":"Nat. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2576","DOI":"10.3389\/fimmu.2018.02576","article-title":"Microglia: Immune regulators of neurodevelopment","volume":"9","author":"Cowan","year":"2018","journal-title":"Front. Lmmunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1083\/jcb.201709069","article-title":"Microglia in Alzheimer\u2019s disease","volume":"217","author":"Hansen","year":"2018","journal-title":"J. Cell. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1146\/annurev-immunol-051116-052358","article-title":"Microglia function in the central nervous system during health and neurodegeneration","volume":"35","author":"Colonna","year":"2017","journal-title":"Annu. Rev. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Dong, Y., Li, X., Cheng, J., and Hou, L. (2019). Drug development for Alzheimer\u2019s disease: Microglia induced neuroinflammation as a target?. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030558"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"514","DOI":"10.3389\/fncel.2019.00514","article-title":"Pharmacological targeting of microglial activation: New therapeutic approach","volume":"13","author":"Liu","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/0896-6273(94)90331-X","article-title":"Acetylcholinesterase density and turnover number at frog neuromuscular\u2013junctions, with modeling of their role in synaptic function","volume":"12","author":"Anglister","year":"1994","journal-title":"Neuron"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2174\/1570159X13666150716165726","article-title":"Alzheimer\u2019s disease: Targeting the cholinergic system","volume":"14","author":"Guimaraes","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1039\/b508966m","article-title":"Acetylcholinesterase inhibitors from plants and fungi","volume":"23","author":"Houghton","year":"2006","journal-title":"J. Nat. Prod. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S0896-6273(00)80108-7","article-title":"Acetylcholinesterase accelerates assembly of amyloid-\u03b2-peptides into Alzheimer\u2019s fibrils: Possible role of the peripheral site of the enzyme","volume":"16","author":"Inestrosa","year":"1996","journal-title":"Neuron"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3213","DOI":"10.1523\/JNEUROSCI.18-09-03213.1998","article-title":"Stable complexes involving acetylcholinesterase and amyloid-beta peptide change the biochemical properties of the enzyme and increase the neurotoxicity of Alzheimer\u2019s fibrils","volume":"18","author":"Alvarez","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1002\/iub.1386","article-title":"Endoplasmic reticulum quality control and systemic amyloid disease: Impacting protein stability from the inside out","volume":"67","author":"Chen","year":"2015","journal-title":"IUBMB Life"},{"key":"ref_52","first-page":"349","article-title":"Multi-target directed drugs as a modem approach for drug design towards Alzheimer\u2019s disease: An update","volume":"25","author":"Dias","year":"2018","journal-title":"Curr. Med. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.trci.2019.05.008","article-title":"Alzheimer\u2019s disease drug development pipeline","volume":"5","author":"Cummings","year":"2019","journal-title":"Alzheimer\u2019s Dement. Transl. Res. Clin. Interv."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.ejmech.2019.02.076","article-title":"Advancement of multi-target drug discoveries and promising applications in the field of Alzheimer\u2019s disease","volume":"169","author":"Wang","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_55","unstructured":"Koslow, T. (2007). The Silent Deep: The Discovery, Ecology and Consertvation of the Deep Sea, University Chicago Press."},{"key":"ref_56","first-page":"228","article-title":"Deep sea as a source of novel anticancer drugs: Update on discovery and preclinical\/clinical evaluation in a systems medicine perspective","volume":"14","author":"Russo","year":"2015","journal-title":"EXCLI J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1007\/s00018-006-6264-7","article-title":"Characterization of apoptosis induced by marine natural products in non small cell lung cancer A549 cells","volume":"63","author":"Catassi","year":"2006","journal-title":"Cell Mol. Life Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.2174\/092986711796642652","article-title":"From the sea to anticancer therapy","volume":"18","author":"Russo","year":"2011","journal-title":"Curr. Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"218","DOI":"10.2174\/157489212799972963","article-title":"Anticancer drug discovery from the marine environment","volume":"7","author":"Nastrucci","year":"2012","journal-title":"Recent Pat. Anticancer Drug Discov."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.2174\/138945012802009035","article-title":"New anticancer drugs from marine cyanobacteria","volume":"13","author":"Russo","year":"2012","journal-title":"Curr. Drug Targets"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1517\/13543776.15.10.1377","article-title":"Marine compounds for the therapeutic treatment of neurological disorders","volume":"15","author":"Alonso","year":"2005","journal-title":"Expert Opin. Ther. Pat."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.3390\/md12021066","article-title":"Marketed marine natural products in the pharmaceutical and cosmeceutical industries: Tips for success","volume":"12","author":"Martins","year":"2014","journal-title":"Mar. Drugs"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.chembiol.2011.12.014","article-title":"Lessons from the past and charting the future of marine natural products drug discovery and chemical biology","volume":"19","author":"Gerwick","year":"2012","journal-title":"Chem. Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1146\/annurev.arplant.59.032607.092730","article-title":"Alkaloids biosynthesis: Methods and trafficking","volume":"59","author":"Ziegler","year":"2008","journal-title":"Annu. Rev. Plant Biol."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Roberts, M.F., and Wink, M. (1998). Chemical taxonomy of alkaloids. Alkaloids, Biochemistry, Ecology and Medicinal Applications, Plenum Press.","DOI":"10.1007\/978-1-4757-2905-4"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"4209","DOI":"10.1039\/c2ra20322g","article-title":"New dictyodendrins as BACE inhibitors from a Southern Australian marine sponge Ianthella sp.","volume":"2","author":"Zhang","year":"2012","journal-title":"RSC Adv."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1039\/c2ob06747a","article-title":"A search for BACE inhibitors reveals new biosynthetically related pyrrolidones, furanones and pyrroles from a southern Australian marine sponge Ianthella sp.","volume":"10","author":"Zhang","year":"2012","journal-title":"Org. Biomol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.1016\/j.chembiol.2003.11.010","article-title":"GSK-3-selective inhibitors derived from tyrian purple indirubins","volume":"10","author":"Meijer","year":"2003","journal-title":"Chem. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1021\/np0601399","article-title":"Manzamine B and E and ircinal A related alkaloids from an indonesian Acanthostrongylophora sponge and their activity against infectious, tropical parasitic, and Alzheimer\u2019s diseases","volume":"69","author":"Raot","year":"2006","journal-title":"J. Nat. Prod."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.1016\/j.bmcl.2004.01.050","article-title":"Meridianins, a new family of protein kinase inhibitors isolated from the ascidian Aplidium meridianum","volume":"14","author":"Gompel","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1021\/jm700940h","article-title":"Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): Synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2\/cyclin A\/meriolin complex","volume":"51","author":"Echalier","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.2174\/1568026614666140324142409","article-title":"Indole alkaloids and semisynthetic indole derivatives asmultifunctional scaffolds aiming the inhibition of enzymes related to neurodegenerative diseases\u2014A focus on Psychotria L. Genus","volume":"14","author":"Passos","year":"2014","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"6032","DOI":"10.1016\/j.bmc.2009.06.054","article-title":"The marine natural-derived inhibitors of glycogen synthase kinase-3 beta- phenylmethylene hydantoins: Ln vitro and in vivo activities and pharmacophore modeling","volume":"17","author":"Khanfar","year":"2009","journal-title":"Bioorg. Med. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1002\/cmdc.201200169","article-title":"Kinase inhibitor scaffolds against neurodegenerative diseases from a Southern Australian ascidian, Didemnum sp.","volume":"7","author":"Plisson","year":"2012","journal-title":"Chem. Med. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/j.neuint.2011.08.013","article-title":"13-Desmethyl spirolide-C is neuroprotective and reduces intracellular A\u03b2 and hyperphosphorylated tau in vitro","volume":"59","author":"Alonso","year":"2011","journal-title":"Neurochem. Int."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3784","DOI":"10.1016\/j.tetlet.2012.05.051","article-title":"A search for kinase inhibitors and antibacterial agents: Bromopyrrolo-2- amino-imidazoles from a deep-water Great Australian Bight sponge Axinella sp.","volume":"53","author":"Zhang","year":"2012","journal-title":"Tetrahedron Lett."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.chembiol.2010.11.009","article-title":"Specific CLK inhibitors from a novel chemotype for regulation of alternative splicing","volume":"18","author":"Fedorov","year":"2011","journal-title":"Chem. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"689","DOI":"10.3390\/md7040689","article-title":"The antinociceptive and anti-inflammatory activities of caulerpin, a bisindole alkaloid isolated from seaweeds of the genus Caulerpa","volume":"7","year":"2009","journal-title":"Mar. Drugs"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Kim, M.E., Jung, I., Na, J.Y., Lee, Y., Lee, J., Lee, J.S., and Lee, J.S. (2018). Pseudane-VII regulates LPS-induced neuroinflammation in brain microglia cells through the inhibition of iNOS expression. Molecules, 23.","DOI":"10.3390\/molecules23123196"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1039\/C9NP00010K","article-title":"Natural cholinesterase inhibitors from marine organisms","volume":"36","author":"Moodie","year":"2019","journal-title":"Nat. Prod. Rep."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1021\/np2009626","article-title":"Geranylphenazinediol, an acetylcholinesterase inhibitor produced by a Streptomyces species","volume":"75","author":"Ohlendorf","year":"2012","journal-title":"J. Nat. Prod."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"831","DOI":"10.7164\/antibiotics.54.831","article-title":"Quinolactacins A1 and A2, new acetylcholinesterase inhibitors from Penicillium citrinum","volume":"54","author":"Kim","year":"2001","journal-title":"J. Antibiot."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"760","DOI":"10.3389\/fphar.2020.00760","article-title":"Circumdatin D exerts neuroprotective effects by attenuating LPS-induced pro  inflammatory responses and downregulating acetylcholinesterase activity in vitro and in vivo","volume":"11","author":"Zhang","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1021\/acsomega.7b00127","article-title":"N-Methyl-beta-carbolinium Salts and an N-Methylated 8-oxoisoguanine as acetylcholinesterase inhibitors from a solitary ascidian, Cnemidocarpa irene","volume":"2","author":"Tadokoro","year":"2017","journal-title":"ACS Omega"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"9063","DOI":"10.1016\/S0040-4020(00)00759-6","article-title":"Turbotoxins A and B, novel diiodotyramine derivatives from the Japanese gastropod Turbo marmorata","volume":"56","author":"Kigoshi","year":"2000","journal-title":"Tetrahedron"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1021\/np401002s","article-title":"Isolation and Synthesis of Pulmonarins A and B, acetylcholinesterase inhibitors from the colonial ascidian Synoicum pulmonaria","volume":"77","author":"Tadesse","year":"2014","journal-title":"J. Nat. Prod."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.ejmech.2017.05.019","article-title":"Discorhabdin alkaloids from Antarctic Latrunculia spp. sponges as a new class of cholinesterase inhibitors","volume":"136","author":"Defant","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"6560","DOI":"10.1016\/j.bmc.2008.05.027","article-title":"Petrosamine, a potent anticholinesterase pyridoacridine alkaloid from a Thai marine sponge Petrosia n. sp.","volume":"16","author":"Nukoolkarn","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"11220","DOI":"10.1039\/C6OB02120D","article-title":"Synthetic analogs of stryphnusin isolated from the marine sponge Stryphnus fortis inhibit acetylcholinesterase with no effect on muscle function or neuromuscular transmission","volume":"14","author":"Moodie","year":"2016","journal-title":"Org. Biomol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1071\/CH9891427","article-title":"2 Bromotyrosine-derived metabolites from an australian marine sponge Aplysina sp.","volume":"42","author":"Xynas","year":"1989","journal-title":"Aust. J. Chem."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/S0167-4838(98)00125-3","article-title":"Inhibition of acetylcholinesterase by an alkylpyridinium polymer from the marine sponge, Reniera sarai","volume":"1387","author":"Marcel","year":"1998","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"3761","DOI":"10.1002\/ejoc.201100434","article-title":"New structural insights into saraines A, B, and C, macrocyclic alkaloids from the Mediterranean sponge Reniera (Haliclona) sarai","volume":"2011","author":"Defant","year":"2011","journal-title":"Eur. J. Org. Chem."},{"key":"ref_93","first-page":"356","article-title":"Bioactivity screening of selected Turkish marine sponges and three compounds from Agelas oroides","volume":"6","author":"Orhan","year":"2012","journal-title":"Rec. Nat. Prod."},{"key":"ref_94","first-page":"979","article-title":"Anabaseine is a potent agonist on muscle and neuronal alphabungarotoxin-sensitive nicotinic receptors","volume":"283","author":"Kem","year":"1997","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1039\/c2md20076g","article-title":"Total synthesis and anti-cholinesterase activity of marine-derived bis-indole alkaloid fascaplysin","volume":"3","author":"Bharate","year":"2012","journal-title":"Med. Chem. Comm."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.lfs.2018.07.036","article-title":"Exploring the potential of marine microbes in clinical management of Alzheimer\u2019s disease: A road map for bioprospecting and identifying promising isolates","volume":"208","author":"Muralidharan","year":"2018","journal-title":"Life Sci."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s12272-014-0503-5","article-title":"Natural products from marine organisms with neuroprotective activity in the experimental models of Alzheimer\u2019s disease, Parkinson\u2019s disease and ischemic brain stroke: Their molecular targets and action mechanisms","volume":"38","author":"Choi","year":"2015","journal-title":"Arch. Pharm. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1021\/np0400095","article-title":"Three new manzamine alkaloids from a common Indonesian sponge and their activity against infectious and tropical parasitic diseases","volume":"67","author":"Rao","year":"2004","journal-title":"J. Nat. Prod."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3512","DOI":"10.1021\/jm030475b","article-title":"New manzamine alkaloids from an indo-pacific sponge. Pharmacokinetics, oral availability, and the significant activity of several manzamines against HIV-I, AIDS opportunistic infections, and inflammatory diseases","volume":"47","author":"Yousaf","year":"2004","journal-title":"J. Med. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"13382","DOI":"10.1021\/ja030087z","article-title":"Manadomanzamines A and B: A novel alkaloid ring system with potent activity against mycobacteria and HIV-1","volume":"125","author":"Peng","year":"2003","journal-title":"J. Am. Chem. Soc."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"618","DOI":"10.2174\/138955712800626728","article-title":"Meridianins: Marine-derived potent kinase inhibitors","volume":"12","author":"Bharate","year":"2012","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1021\/np970493u","article-title":"Indole alkaloids from the tunicate Aplidium meridianum","volume":"61","author":"Franco","year":"1998","journal-title":"J. Nat. Prod."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1071\/CH10042","article-title":"Synthesis and structure reassessment of psammopemmin A","volume":"63","author":"Lebar","year":"2010","journal-title":"Aust. J. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"4474","DOI":"10.1021\/jm200464w","article-title":"Synthesis, protein kinase inhibitory potencies, and in vitro antiproliferative activities of meridianin derivatives","volume":"54","author":"Giraud","year":"2011","journal-title":"J. Med. Chem."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"9312","DOI":"10.1021\/jm301034u","article-title":"Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B","volume":"55","author":"Tahtouh","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"3987","DOI":"10.1016\/S0040-4020(01)89673-3","article-title":"Alkaloids from the Antarctic sponge Kirkpatrickia varialosa. Part 1: Variolin B, a new antitumour and antiviral compound","volume":"50","author":"Perry","year":"1994","journal-title":"Tetrahedron"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2873","DOI":"10.1016\/j.tetlet.2012.03.126","article-title":"Kororamide A, a new tribrominated \u00edndole alkaloid from australian bryozoan Amathia tortuosa","volume":"53","author":"Carroll","year":"2012","journal-title":"Tetrahedron Lett."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"7879","DOI":"10.1016\/j.tet.2015.08.017","article-title":"Korforamide B, a brominated alkloid from the bryozoan Amathia tortuosa and its effects on Parkinson\u2019s disease cells","volume":"71","author":"Dashti","year":"2015","journal-title":"Tetrahedron"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.lfs.2005.09.007","article-title":"Indole alkaloid marine natural products: An established source of cancer drug leads with considerable promise for the control of parasitic, neurological and other diseases","volume":"78","author":"Gul","year":"2005","journal-title":"Life Sci."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Ciavatta, M.L., Lefranc, F., Vieira, L.M., Kiss, R., Carbone, M., van Otterlo, W.A.L., Lopanik, N.B., and Waeschenbach, A. (2020). The phylum bryozoa: From biology to biomedical potential. Mar. Drugs, 18.","DOI":"10.3390\/md18040200"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"3254","DOI":"10.1021\/jo962132+","article-title":"Ningalins A-D: Novel aromatic alkaloids from a Western Australian ascidian of the genus Didemnum","volume":"62","author":"Kang","year":"1997","journal-title":"J. Org. Chem."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"8659","DOI":"10.1016\/S0040-4020(01)00861-4","article-title":"Assignment of the relative stereochemistry of the spirolides, macrocyclic toxins isolated from shellfish and from the cultured dinoflagellate Alexandrium ostenfeldii","volume":"57","author":"Falk","year":"2001","journal-title":"Tetrahedron"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1515\/znc-1995-9-1012","article-title":"Bioactive alkaloids from the tropical marine sponge Axinella carteri","volume":"50","author":"Supriyono","year":"1995","journal-title":"Z. F\u00fcr Nat. C"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S1074-5521(00)00063-6","article-title":"Inhibition of cyclin-dependent kinases, GSK3\u03b2 and CK1 by hymenialdisine, a marine sponge constituent","volume":"7","author":"Meijer","year":"2000","journal-title":"Chem. Biol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1039\/c39800000435","article-title":"Characterization of a yellow compound isolated from the marine sponge Phakellia flabellate","volume":"10","author":"Sharma","year":"1980","journal-title":"J. Chem. Soc. Chem. Comm."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"8744","DOI":"10.1021\/ja9717828","article-title":"Eleutherobin, a new cytotoxin that mimics paclitaxel (Taxol) by stabilizing microtubules","volume":"119","author":"Lindel","year":"1997","journal-title":"J. Am. Chem. Soc."},{"key":"ref_117","first-page":"1111","article-title":"Eleutherobin, a novel cytotoxic agent that induces tubulin polymerization, is similar to paclitaxel (Taxol (R))","volume":"58","author":"Long","year":"1998","journal-title":"Cancer Res."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1002\/hlca.19870700807","article-title":"Novel diterpenoidic alcohols esterified by (E)-N(l)-methylurocanic acid. Isolation from the Mediterranean stolonifer Sarcodictyon roseum","volume":"70","author":"Guerriero","year":"1987","journal-title":"Helv. Chim. Acta"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1002\/hlca.19880710504","article-title":"lsolation from the Mediterranean stolonifern coral Sarcodictyon roseum of sarcodictyin C, D, E, and P, novel diterpenoidic alcohols esterified by (E)- or (Z)-N(1)-methylurocanic acid. Failure of the carbon-skeleton type as a classification criterion","volume":"71","author":"Guerriero","year":"1988","journal-title":"Helv. Chim. Acta."},{"key":"ref_120","first-page":"5","article-title":"Sarcodictyins: A new class of marine derivatives with mode of action similar to Taxol. Abstract 30","volume":"38","author":"Ciomei","year":"1997","journal-title":"Proc. Am. Ass. Canc. Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"4934","DOI":"10.3390\/md12094934","article-title":"Bioactive Compounds from Macroalgae in the New Millennium: Implications for Neurodegenerative Diseases","volume":"12","author":"Barbosa","year":"2014","journal-title":"Mar. Drugs."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Kim, M.E., Jung, I., Lee, J.S., Na, J.Y., Kim, W.J., Kim, Y.O., and Park, Y.D. (2017). Pseudane-VII isolated from Pseudoalteromonas sp. M2 ameliorates LPS-induced inflammatory response in vitro and in vivo. Mar. Drugs., 15.","DOI":"10.3390\/md15110336"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.fitote.2015.01.014","article-title":"Acetylcholinesterase inhibitory dimeric indole derivatives from the marine actinomycetes Rubrobacter radiotolerans","volume":"102","author":"Li","year":"2015","journal-title":"Fitoterapia"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"578","DOI":"10.3390\/md6040578","article-title":"Acetylcholinesterase-inhibiting activity of pyrrole derivatives from a novel marine gliding bacterium, Rapidithrix thailandica","volume":"6","author":"Sangnoi","year":"2008","journal-title":"Mar. Drugs"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/cbdv.201200343","article-title":"Acethylcholinesterase-inhibitory activities of the extracts from sponges collected in Mauritius waters","volume":"10","author":"Beedessee","year":"2013","journal-title":"Chem. Biodivers."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1515\/BOT.2008.014","article-title":"Sponge-associated fungi and their bioactive compounds: The Suberites case","volume":"51","author":"Proksch","year":"2008","journal-title":"Bot. Mar."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Cheng, Z.Q., Song, J.L., Zhu, K., Zhang, J., Jiang, C.S., and Zhang, H. (2018). Total synthesis of pulmonarin B and design of brominated phenylacetic acid\/tacrine hybrids: Marine pharmacophore inspired discovery of neu Che and A\u03b2 aggregation inhibitors. Mar. Drugs, 16.","DOI":"10.3390\/md16090293"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1021\/np50124a020","article-title":"Discorhabdin alkaloids from the Antarctic sponge Latrunculia apicalis","volume":"58","author":"Yang","year":"1995","journal-title":"J. Nat. Prod."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1021\/np034084b","article-title":"Cytotoxic pyrroloiminoquinones from four new species of south African latrunculide sponges","volume":"67","author":"Antunes","year":"2004","journal-title":"J. Nat. Prod."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1727","DOI":"10.1016\/S0040-4020(01)86737-5","article-title":"Cytotoxic pigments from New Zealand sponges of the genus Latrunculia: Discorhabdin-A, Discorhabdin-B and Discorhabdin-C","volume":"44","author":"Perry","year":"1988","journal-title":"Tetrahedron"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1021\/np0303761","article-title":"Discorhabdins I and L, cytotoxic alkaloids from the sponge Latrunculia brevis","volume":"67","author":"Reyes","year":"2004","journal-title":"J. Nat. Prod."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"3283","DOI":"10.1016\/S0040-4039(00)84776-0","article-title":"Studies of Swedish marine organisms 7. A novel biologically active indole alkaloid from the sponge Geodia baretti","volume":"27","author":"Lidgren","year":"1986","journal-title":"Tetrahedron Lett."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"3385","DOI":"10.1016\/S0040-4039(02)00470-7","article-title":"Barettin, revisited?","volume":"43","author":"Dieckmann","year":"2002","journal-title":"Tetrahedron Lett."},{"key":"ref_134","first-page":"1559","article-title":"Non-competitive inhibition of acetylcholinesterase by bromotyrosine alkaloids","volume":"9","author":"Olatunji","year":"2014","journal-title":"Nat. Prod. Commun."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1021\/np020275n","article-title":"Purealidin S and purpuramine J, bromotyrosine alkaloids from the Fijian marine sponge Druinella sp.","volume":"65","author":"Tabudravu","year":"2002","journal-title":"J. Nat. Prod."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1021\/np50099a025","article-title":"3 New bromotyrosine-derived metabolites of the sponge Psammaplysilla purpurea","volume":"56","author":"Jurek","year":"1993","journal-title":"J. Nat. Prod."},{"key":"ref_137","first-page":"181","article-title":"Antibacterial and anticholinesterase activities of aplysamine-4, a bromotyrosine-derived metabolite of a Red Sea marine sponge","volume":"10","author":"Mancin","year":"2001","journal-title":"J. Nat. Toxins"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1039\/p19720000018","article-title":"Aerothionin and homoaerothionin\u20142 tetrabromo spirocyclohexadienylisoxazoles from Verongia sponges","volume":"1","author":"Moody","year":"1972","journal-title":"JCS Perkin I."},{"key":"ref_139","first-page":"1945","article-title":"Bromotyrosine alkaloids with acetylcholinesterase inhibitory activity from the Thai sponge Acanthodendrilla sp.","volume":"10","author":"Sirimangkalakitti","year":"2015","journal-title":"Nat. Prod. Commun."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"3921","DOI":"10.1016\/S0040-4039(01)86465-0","article-title":"Marine natural-products\u2014Fistularin-1, fistularin 2 and fistularin-3 from the sponge Aplysina fistularis forma fluva","volume":"20","author":"Gopichand","year":"1979","journal-title":"Tetrahedron Lett."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1351\/pac198658030375","article-title":"Marine natural products: New results from Mediterranean invertebrates","volume":"58","author":"Cimino","year":"1986","journal-title":"Pure Appl. Chem."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1002\/bscb.19860950907","article-title":"Sarains A new class of alkaloids from the marine sponge Reniera sarai","volume":"95","author":"Cimino","year":"1986","journal-title":"Bull. Soc. Chim. Belg."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"3863","DOI":"10.1016\/S0040-4020(01)89245-0","article-title":"Unprecedented alkaloid skeleton from the Mediterranean sponge Reniera sarai: X-ray structure of an acetate derivative of sarain-A","volume":"45","author":"Cimino","year":"1989","journal-title":"Tetrahedron"},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0040-4039(01)80344-0","article-title":"Isosarain-1: A new alkaloid from the Mediterranean sponge Reniera sarai","volume":"30","author":"Cimino","year":"1989","journal-title":"Tetrahedron Lett."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"14961","DOI":"10.1016\/0040-4020(96)00908-8","article-title":"Further studies of alkaloids from Reniera sarai: Structures of saraine-3 and isosaraine-3, absolute stereochemistry of saraine-1 and saraine-2","volume":"52","author":"Guo","year":"1996","journal-title":"Tetrahedron"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S0040-4039(97)10576-7","article-title":"Absolute stereochemistry of isosaraine-1 and isosaraine-2","volume":"39","author":"Guo","year":"1998","journal-title":"Tetrahedron Lett."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.steroids.2007.05.005","article-title":"Acetylcholinesterase-inhibiting steroidal alkaloid from the sponge Corticium sp.","volume":"72","author":"Langjae","year":"2007","journal-title":"Steroids"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1039\/c29710001129","article-title":"New bromo-pyrrole derivatives from the sponge Agelas oroides","volume":"18","author":"Forenza","year":"1971","journal-title":"J. Chem. Soc. D Chem. Commun."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1039\/c39730000078","article-title":"Reinvestigation into the structure of oroidin, a bromopyrrole derivative from a marine sponge","volume":"33","author":"Garcia","year":"1973","journal-title":"J. Chem. Soc. Chem. Commun."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0041-0101(94)00153-Y","article-title":"Inhibition of acetylcholinesterase by a pseudozoanthoxanthin-like compound isolated from the zoanthid Parazoanthus axinellae (O. Schmidt)","volume":"33","author":"Turk","year":"1995","journal-title":"Toxicon"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"R315","DOI":"10.1007\/BF02346395","article-title":"Pseudozo-anthoxantin-like compound from Parazoanthus axinellae Adriaticus inhibits acetylcholinesterase","volume":"431","author":"Turk","year":"1996","journal-title":"Pflugers Arch."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1139\/v79-273","article-title":"Pseudo-zoanthoxanthins from gold coral","volume":"57","author":"Schwartz","year":"1979","journal-title":"Can. J. Chem."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1021\/acschemneuro.7b00416","article-title":"In silico identification and experimental validation of novel anti-Alzheimer\u2019s multitargeted ligands from a marine source featuring a \u201c2-aminoimidazole plus aromatic group\u201d scaffold","volume":"9","author":"Vitale","year":"2018","journal-title":"ACS Chem. Neurosci."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"4163","DOI":"10.1021\/jo00221a041","article-title":"Stevensine, a novel alkaloid of an unidentified sponge","volume":"50","author":"Albizati","year":"1985","journal-title":"J. Org. Chem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0041-0101(71)90039-0","article-title":"Isolation and structure of a hoplonemertine toxin","volume":"9","author":"Coates","year":"1971","journal-title":"Toxicon"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.neuropharm.2004.01.005","article-title":"Effects at a distance in \u03b17 nAChR selective agonists: Benzylidene substitutions that regulate potency and efficacy","volume":"46","author":"Papke","year":"2004","journal-title":"Neuropharmacology"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1126\/science.211.4486.1051","article-title":"Anabaseine: Venom alkaloid of Aphaenogaster ants","volume":"211","author":"Wheeler","year":"1981","journal-title":"Science"},{"key":"ref_158","first-page":"105","article-title":"Marine pharmacology: Potentialities in the treatment of infectious diseases, osteoporosis and Alzheimer\u2019s disease","volume":"97","author":"Kornprobst","year":"2005","journal-title":"Adv. Biochem. Engin\/Biotechnol."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/nrmicro2839","article-title":"Genomic insights into the marine sponge microbiome","volume":"10","author":"Hentschel","year":"2012","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejmech.2015.10.049","article-title":"Discovery of a marine-derived bis-indole alkaloid fascaplysin, as a new class of potent P-glycoprotein inducer and establishement of its structure\u2013activity relationship","volume":"107","author":"Manda","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Sun, Q., Liu, F., Sang, J., Lin, M., Ma, J., Xiao, X., Yan, S., Naman, C.B., Wang, N., and He, S. (2019). 9-Methyl -fascaplysin is a more potent A\u03b2 aggregation inhibitor than the marine-derived alkaloid, fascaplysin, and produces nanomolar neuroprotective effects in SH-SY5Y cells. Mar. Drugs, 17.","DOI":"10.3390\/md17020121"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"4741","DOI":"10.1021\/acschemneuro.9b00503","article-title":"Fascaplysin derivatives are potent multitarget agents against Alzheimer\u2019s disease: In vitro and in vivo evidence","volume":"10","author":"Pan","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1039\/C4NP00144C","article-title":"Marine natural products","volume":"32","author":"Blunt","year":"2015","journal-title":"Nat. Prod. Rep."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1021\/jm7009364","article-title":"Multi-target-directed ligands to combat neurodeghenerative diseases","volume":"51","author":"Cavalli","year":"2008","journal-title":"J. Med. Chem."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1021\/acs.jmedchem.9b00017","article-title":"Rational design of multitarget-directed ligands: Strategies and emerging paradigms","volume":"62","author":"Zhou","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1039\/C4MD00069B","article-title":"Two disease, one approach: Multitarget drug discovery in Alzheimer\u2019s and neglected tropical diseases","volume":"5","author":"Prati","year":"2014","journal-title":"Med. Chem. 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