{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T03:29:05Z","timestamp":1789010945528,"version":"build-2803163510"},"reference-count":83,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022863","name":"Statistical Society of Australia","doi-asserted-by":"publisher","award":["NBC-5-C-2316"],"award-info":[{"award-number":["NBC-5-C-2316"]}],"id":[{"id":"10.13039\/501100022863","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001671","name":"European Synchrotron Radiation Facility","doi-asserted-by":"publisher","award":["mx2691"],"award-info":[{"award-number":["mx2691"]}],"id":[{"id":"10.13039\/501100001671","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["PNC-E3-2022-23683266 PNC-HLS-DA"],"award-info":[{"award-number":["PNC-E3-2022-23683266 PNC-HLS-DA"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["CUP C 43C22001630001"],"award-info":[{"award-number":["CUP C 43C22001630001"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["2022LWZ77\\u202FN"],"award-info":[{"award-number":["2022LWZ77\\u202FN"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["DGA \/ SSA NBC -5-C-2316"],"award-info":[{"award-number":["DGA \/ SSA NBC -5-C-2316"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100024370","name":"Ministero dell'Istruzione dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100024370","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006021","name":"Direction G\u00e9n\u00e9rale de l\u2019Armement","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006021","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004769","name":"Universit\u00e0 degli Studi di Pavia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2026,10]]},"DOI":"10.1016\/j.ejmech.2026.118961","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T04:03:06Z","timestamp":1778817786000},"page":"118961","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":1,"special_numbering":"C","title":["Leveraging multitargeting BChE-MAO B inhibitors against microglia-related neuroinflammation: in vitro biological evaluation, structure-activity relationships, drug-like properties, and X-ray crystal complexes"],"prefix":"10.1016","volume":"316","author":[{"given":"Mariagrazia","family":"Rullo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"La Spada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Brazzolotto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Marchese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imane Ghafir","family":"El Idrissi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morena","family":"Miciaccia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Colella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose M.","family":"Brea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Macchia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria I.","family":"Loza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Gottinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Scilimati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Perrone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Stefanachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Binda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Leonetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4198-3897","authenticated-orcid":false,"given":"Leonardo","family":"Pisani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2026.118961_bib1","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/S1474-4422(16)00062-4","article-title":"Defeating Alzheimer's disease and other dementias: a priority for European science and society","volume":"15","author":"Winblad","year":"2016","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.ejmech.2026.118961_bib2","article-title":"2025 Alzheimer's disease facts and figures","volume":"21","year":"2025","journal-title":"Alzheimer's Dement."},{"key":"10.1016\/j.ejmech.2026.118961_bib3","doi-asserted-by":"crossref","DOI":"10.1016\/j.cell.2019.09.001","article-title":"Alzheimer disease: an update on pathobiology and treatment strategies","author":"Long","year":"2019","journal-title":"Cell."},{"key":"10.1016\/j.ejmech.2026.118961_bib4","article-title":"Alzheimer's disease drug development pipeline: 2025, Alzheimer's dement","volume":"11","author":"Cummings","year":"2025","journal-title":"Transl. Res. Clin. Interv."},{"key":"10.1016\/j.ejmech.2026.118961_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/S0021-9258(17)38495-8","article-title":"Microtubule-associated protein tau. A component of Alzheimer paired helical filaments","author":"Grundke-Iqbal","year":"1986","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib6","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/0197-4580(91)90006-6","article-title":"The distribution of tangles, plaques and related immunohistochemical markers in healthy aging and Alzheimer's disease","volume":"12","author":"Price","year":"1991","journal-title":"Neurobiol. Aging"},{"key":"10.1016\/j.ejmech.2026.118961_bib7","doi-asserted-by":"crossref","DOI":"10.1097\/00005072-199704000-00001","article-title":"The pathogenesis of senile plaques","author":"Dickson","year":"1997","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"10.1016\/j.ejmech.2026.118961_bib8","doi-asserted-by":"crossref","first-page":"4245","DOI":"10.1073\/pnas.82.12.4245","article-title":"Amyloid plaque core protein in Alzheimer disease and Down syndrome","volume":"82","author":"Masters","year":"1985","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.ejmech.2026.118961_bib9","doi-asserted-by":"crossref","DOI":"10.1038\/197192b0","article-title":"Paired helical filaments in electron microscopy of Alzheimer's disease","author":"Kidd","year":"1963","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2026.118961_bib10","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1056\/NEJMra0909142","article-title":"Alzheimer's disease: mechanism of disease","volume":"362","author":"Querfurth","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.ejmech.2026.118961_bib11","doi-asserted-by":"crossref","first-page":"794","DOI":"10.1038\/nn.4017","article-title":"The case for rejecting the amyloid cascade hypothesis","volume":"18","author":"Herrup","year":"2015","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.ejmech.2026.118961_bib12","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/S1474-4422(10)70223-4","article-title":"Position Paper Revising the defi nition of Alzheimer's disease: a new lexicon","volume":"9","author":"Dubois","year":"2010","journal-title":"Lancet Neurol."},{"key":"10.1016\/j.ejmech.2026.118961_bib13","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1038\/s41577-024-01104-7","article-title":"Neuroinflammation in Alzheimer disease","volume":"25","author":"Heneka","year":"2025","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.ejmech.2026.118961_bib14","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1038\/s41582-020-00435-y","article-title":"Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?","volume":"17","author":"Leng","year":"2021","journal-title":"Nat. Rev. Neurol."},{"key":"10.1016\/j.ejmech.2026.118961_bib15","doi-asserted-by":"crossref","DOI":"10.1016\/S0140-6736(23)01478-2","article-title":"The pathogenesis of Parkinson's disease","author":"Morris","year":"2024","journal-title":"Lancet."},{"key":"10.1016\/j.ejmech.2026.118961_bib16","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.brainresrev.2009.11.004","article-title":"Neuroglia in neurodegeneration","volume":"63","author":"Heneka","year":"2010","journal-title":"Brain Res. Rev."},{"key":"10.1016\/j.ejmech.2026.118961_bib17","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.molmed.2018.11.006","article-title":"Astrocyte biomarkers in alzheimer's disease","volume":"25","author":"Carter","year":"2019","journal-title":"Trends Mol. Med."},{"key":"10.1016\/j.ejmech.2026.118961_bib18","doi-asserted-by":"crossref","first-page":"2960","DOI":"10.1016\/j.fmre.2024.12.023","article-title":"Glial cell crosstalk in Parkinson's disease: mechanisms, implications, and therapeutic strategies","volume":"5","author":"Wang","year":"2025","journal-title":"Fundam. Res."},{"key":"10.1016\/j.ejmech.2026.118961_bib19","article-title":"The effects of microglia-associated neuroinflammation on Alzheimer's disease","volume":"14","author":"Wang","year":"2023","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ejmech.2026.118961_bib20","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1093\/brain\/awac096","article-title":"Reimagining cholinergic therapy for Alzheimer's disease","volume":"145","author":"Giacobini","year":"2022","journal-title":"Brain"},{"key":"10.1016\/j.ejmech.2026.118961_bib21","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/d41586-023-00030-3","article-title":"FDA approves Alzheimer's drug lecanemab amid safety concerns","volume":"613","author":"Reardon","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.ejmech.2026.118961_bib22","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1021\/acs.jmedchem.8b00760","article-title":"Polypharmacology by design: a medicinal chemist's perspective on multitargeting compounds","volume":"62","author":"Proschak","year":"2019","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib23","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1021\/acsmedchemlett.9b00039","article-title":"Harnessing polypharmacology with medicinal chemistry","volume":"10","author":"Bolognesi","year":"2019","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2026.118961_bib24","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1002\/med.21699","article-title":"From combinations to multitarget-directed ligands: a continuum in Alzheimer's disease polypharmacology","volume":"41","author":"Albertini","year":"2021","journal-title":"Med. Res. Rev."},{"key":"10.1016\/j.ejmech.2026.118961_bib25","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1002\/ana.410420613","article-title":"Butyrylcholinesterase in the life cycle of amyloid plaques","volume":"42","author":"Guillozet","year":"1997","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.ejmech.2026.118961_bib26","doi-asserted-by":"crossref","first-page":"17213","DOI":"10.1073\/pnas.0508575102","article-title":"Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer beta-amyloid peptide in rodent","volume":"102","author":"Greig","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.ejmech.2026.118961_bib27","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1002\/ana.410340312","article-title":"Neuroglial cholinesterases in the normal brain and in Alzheimer's disease: relationship to plaques, tangles, and patterns of selective vulnerability","volume":"34","author":"Wright","year":"1993","journal-title":"Ann. Neurol."},{"key":"10.1016\/j.ejmech.2026.118961_bib28","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/nrn1035","article-title":"Neurobiology of butyrylcholinesterase","volume":"4","author":"Darvesh","year":"2003","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.ejmech.2026.118961_bib29","doi-asserted-by":"crossref","DOI":"10.1212\/WNL.38.8.1285","article-title":"Reactive microglia are positive for HLA\u2010DR in the substantia nigra of Parkinson's and Alzheimer's disease brains","volume":"38","author":"McGeer","year":"1988","journal-title":"Neurology"},{"key":"10.1016\/j.ejmech.2026.118961_bib30","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1172\/JCI58644","article-title":"Innate immunity in the central nervous system","volume":"122","author":"Ransohoff","year":"2012","journal-title":"J. Clin. Investig."},{"key":"10.1016\/j.ejmech.2026.118961_bib31","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.brainresrev.2004.12.012","article-title":"Innate (inherent) control of brain infection, brain inflammation and brain repair: the role of microglia, astrocytes, \u201cprotective\u201d glial stem cells and stromal ependymal cells","volume":"48","author":"Hauwel","year":"2005","journal-title":"Brain Res. Rev."},{"key":"10.1016\/j.ejmech.2026.118961_bib32","doi-asserted-by":"crossref","DOI":"10.1021\/acs.jmedchem.3c00541","article-title":"Dual-Acting small molecules: Subtype-Selective cannabinoid receptor 2 Agonist\/Butyrylcholinesterase inhibitor hybrids show neuroprotection in an alzheimer's disease mouse model","author":"Spatz","year":"2023","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib33","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2025.118071","article-title":"Discovery of a highly selective BChE inhibitor with concomitant anti-neuroinflammatory activity for treating Alzheimer's disease","volume":"299","author":"Zhao","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib34","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1038\/nrd.2018.97","article-title":"Targeting the NLRP3 inflammasome in inflammatory diseases","volume":"17","author":"Mangan","year":"2018","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2026.118961_bib35","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1038\/s41423-020-0441-8","article-title":"Targeting monoamine oxidase to dampen NLRP3 inflammasome activation in inflammation","volume":"18","author":"S\u00e1nchez-Rodr\u00edguez","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"10.1016\/j.ejmech.2026.118961_bib36","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/0306-4522(94)90311-5","article-title":"Increased monoamine oxidase b activity in plaque-associated astrocytes of Alzheimer brains revealed by quantitative enzyme radioautography","volume":"62","author":"Saura","year":"1994","journal-title":"Neuroscience"},{"key":"10.1016\/j.ejmech.2026.118961_bib37","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1021\/acschemneuro.9b00081","article-title":"Classics in neuroimaging: development of PET tracers for imaging monoamine oxidases","volume":"10","author":"Narayanaswami","year":"2019","journal-title":"ACS Chem. Neurosci."},{"key":"10.1016\/j.ejmech.2026.118961_bib38","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s13195-017-0279-1","article-title":"Monoamine oxidase B is elevated in Alzheimer disease neurons, is associated with \u03b3-secretase and regulates neuronal amyloid \u03b2-peptide levels","volume":"9","author":"Schedin-Weiss","year":"2017","journal-title":"Alzheimers Res. Ther."},{"key":"10.1016\/j.ejmech.2026.118961_bib39","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115352","article-title":"Bioisosteric replacement based on 1,2,4-oxadiazoles in the discovery of 1H-indazole-bearing neuroprotective MAO B inhibitors","volume":"255","author":"Rullo","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib40","doi-asserted-by":"crossref","first-page":"4507","DOI":"10.3390\/molecules24244507","article-title":"Chasing ChEs-MAO B multi-targeting 4-Aminomethyl-7-Benzyloxy-2H-Chromen-2-ones","volume":"24","author":"Rullo","year":"2019","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2026.118961_bib41","doi-asserted-by":"crossref","DOI":"10.3389\/fchem.2022.1002547","article-title":"A twenty-year journey exploring coumarin-based derivatives as bioactive molecules","volume":"10","author":"Pisani","year":"2022","journal-title":"Front. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib42","doi-asserted-by":"crossref","first-page":"891","DOI":"10.3390\/molecules30040891","article-title":"Playing around the coumarin core in the discovery of multimodal compounds directed at alzheimer\u2019s-related targets: a recent literature overview","volume":"30","author":"Rullo","year":"2025","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2026.118961_bib43","doi-asserted-by":"crossref","first-page":"3962","DOI":"10.1021\/acs.jmedchem.1c01784","article-title":"Probing fluorinated motifs onto dual AChE-MAO B inhibitors: rational design, synthesis, biological evaluation, and Early-ADME studies","volume":"65","author":"Rullo","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib44","doi-asserted-by":"crossref","first-page":"14046","DOI":"10.1021\/acs.jmedchem.1c01215","article-title":"Bioisosteres of the phenyl ring: recent strategic applications in lead optimization and drug design","volume":"64","author":"Subbaiah","year":"2021","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib45","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.116511","article-title":"Structure-based design of multitargeting ChEs-MAO B inhibitors based on phenyl ring bioisosteres: ache\/bche selectivity switch and drug-like characterization","volume":"274","author":"La Spada","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib46","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.2174\/1567205013666160404120542","article-title":"Butyrylcholinesterase as a diagnostic and therapeutic target for alzheimer's disease","volume":"13","author":"Darvesh","year":"2016","journal-title":"Curr. Alzheimer Res."},{"key":"10.1016\/j.ejmech.2026.118961_bib47","doi-asserted-by":"crossref","first-page":"5561","DOI":"10.1021\/acs.jmedchem.5b00599","article-title":"Structure-Based design and optimization of multitarget-directed 2 H -Chromen-2-one derivatives as potent inhibitors of monoamine oxidase B and cholinesterases","volume":"58","author":"Farina","year":"2015","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib48","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1021\/acsmedchemlett.2c00001","article-title":"Dual reversible coumarin inhibitors mutually bound to monoamine oxidase B and acetylcholinesterase crystal structures","volume":"13","author":"Ekstr\u00f6m","year":"2022","journal-title":"ACS Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2026.118961_bib49","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1002\/cmdc.201700282","article-title":"Discovery of potent dual binding site acetylcholinesterase inhibitors via Homo- and heterodimerization of coumarin-based moieties","volume":"12","author":"Pisani","year":"2017","journal-title":"ChemMedChem"},{"key":"10.1016\/j.ejmech.2026.118961_bib50","doi-asserted-by":"crossref","first-page":"6791","DOI":"10.1021\/acs.jmedchem.6b00562","article-title":"Exploring basic tail modifications of coumarin-based dual acetylcholinesterase-monoamine oxidase B inhibitors: identification of Water-Soluble, brain-permeant neuroprotective multitarget agents","volume":"59","author":"Pisani","year":"2016","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib51","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2024.116266","article-title":"Novel 6-hydroxybenzothiazol-2-carboxamides as potent and selective monoamine oxidase B inhibitors endowed with neuroprotective activity","volume":"269","author":"Al-Saad","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib52","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/0006-2952(61)90145-9","article-title":"A new and rapid colorimetric determination of acetylcholinesterase activity","volume":"7","author":"Ellman","year":"1961","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejmech.2026.118961_bib53","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1016\/S0140-6736(65)91257-2","article-title":"Tyramine in cheese related to hypertensive crises after monoamine-oxidase inihibition","volume":"1","author":"Blackwelll","year":"1965","journal-title":"Lancet (London, England)"},{"key":"10.1016\/j.ejmech.2026.118961_bib54","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2023.115956","article-title":"Discovery of C-3 isoxazole substituted thiochromone S,S-dioxide derivatives as potent and selective inhibitors for monoamine oxidase B (MAO-B)","volume":"263","author":"Mi","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib55","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2025.108940","article-title":"Discovery of C-3 nitrothiophene substituted thiochromone derivatives as potent and selective human monoamine oxidase B (hMAO-B) inhibitors for the treatment of atherosclerosis","volume":"165","author":"Lin","year":"2025","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib56","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2022.112924","article-title":"Cell models for Alzheimer's and Parkinson's disease: at the interface of biology and drug discovery","author":"Cetin","year":"2022","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.ejmech.2026.118961_bib57","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1021\/acs.jmedchem.9b00797","article-title":"Opportunities and challenges in phenotypic screening for neurodegenerative disease research","volume":"63","author":"Brown","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib58","doi-asserted-by":"crossref","first-page":"2150","DOI":"10.1007\/s11064-012-0838-6","article-title":"Differential toxicity of 6-Hydroxydopamine in SH-SY5Y human neuroblastoma cells and Rat brain Mitochondria: protective role of catalase and superoxide dismutase","volume":"37","author":"Iglesias-Gonz\u00e1lez","year":"2012","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.ejmech.2026.118961_bib59","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.tiv.2005.01.006","article-title":"Effects of 6-hydroxydopamine on mitochondrial function and glutathione status in SH-SY5Y human neuroblastoma cells","volume":"19","author":"Tirmenstein","year":"2005","journal-title":"Toxicol. Vitr."},{"key":"10.1016\/j.ejmech.2026.118961_bib60","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.ejmech.2018.10.043","article-title":"1,2,3,4-Tetrahydroisoquinoline\/2H-chromen-2-one conjugates as nanomolar P-glycoprotein inhibitors: molecular determinants for affinity and selectivity over multidrug resistance associated protein 1","volume":"161","author":"Rullo","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib61","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1186\/s12864-019-5549-9","article-title":"A modular analysis of microglia gene expression, insights into the aged phenotype","volume":"20","author":"Cho","year":"2019","journal-title":"BMC Genom."},{"key":"10.1016\/j.ejmech.2026.118961_bib62","doi-asserted-by":"crossref","DOI":"10.3389\/fneur.2018.00458","article-title":"Interferons in traumatic brain and spinal cord injury: current evidence for translational application","author":"Roselli","year":"2018","journal-title":"Front. Neurol."},{"key":"10.1016\/j.ejmech.2026.118961_bib63","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1128\/IAI.67.1.206-212.1999","article-title":"Gamma Interferon augments macrophage activation by lipopolysaccharide by two distinct mechanisms, at the signal transduction level and via an autocrine mechanism involving tumor necrosis factor alpha and Interleukin-1","volume":"67","author":"Held","year":"1999","journal-title":"Infect. Immun."},{"key":"10.1016\/j.ejmech.2026.118961_bib64","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrn2038","article-title":"Microglia-mediated neurotoxicity: uncovering the molecular mechanisms","volume":"8","author":"Block","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.ejmech.2026.118961_bib65","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/1742-2094-11-98","article-title":"Neuroinflammation and M2 microglia: the good, the bad, and the inflamed","volume":"11","author":"Cherry","year":"2014","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.ejmech.2026.118961_bib66","doi-asserted-by":"crossref","first-page":"9918","DOI":"10.1021\/acs.jmedchem.2c00582","article-title":"Design, synthesis, and biological activity of new CB2 receptor ligands: from orthosteric and allosteric modulators to Dualsteric\/Bitopic ligands","volume":"65","author":"Gado","year":"2022","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib67","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ejmech.2014.10.021","article-title":"Discovery of new 7-substituted-4-imidazolylmethyl coumarins and 4\u2032-substituted-2-imidazolyl acetophenones open analogues as potent and selective inhibitors of steroid-11\u03b2-hydroxylase","volume":"89","author":"Stefanachi","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib68","series-title":"Pharmacokinet. Optim. Drug Res.","first-page":"255","article-title":"Physicochemical parameters as tools in drug discovery and lead optimization","author":"Faller","year":"2001"},{"key":"10.1016\/j.ejmech.2026.118961_bib69","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1021\/jm001020e","article-title":"High-throughput permeability pH profile and high-throughput alkane\/water log P with artificial membranes","volume":"44","author":"Wohnsland","year":"2001","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118961_bib70","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1046\/j.0014-2956.2001.02692.x","article-title":"Engineering of a monomeric and low\u2010glycosylated form of human butyrylcholinesterase","volume":"269","author":"Nachon","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"10.1016\/j.ejmech.2026.118961_bib71","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1111\/j.1742-4658.2012.08672.x","article-title":"Human butyrylcholinesterase produced in insect cells: huprine\u2010based affinity purification and crystal structure","volume":"279","author":"Brazzolotto","year":"2012","journal-title":"FEBS J."},{"key":"10.1016\/j.ejmech.2026.118961_bib72","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1107\/S0909049509036681","article-title":"Edna : a framework for plugin-based applications applied to X-ray experiment online data analysis","volume":"16","author":"Incardona","year":"2009","journal-title":"J. Synchrotron Radiat."},{"key":"10.1016\/j.ejmech.2026.118961_bib73","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1107\/S2059798319011471","article-title":"Macromolecular structure determination using X-rays, neutrons and electrons: recent developments in Phenix","volume":"75","author":"Liebschner","year":"2019","journal-title":"Acta Crystallogr. Sect. D Struct. Biol."},{"key":"10.1016\/j.ejmech.2026.118961_bib74","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1002\/pro.3791","article-title":"Current developments in Coot for macromolecular model building of Electron Cryo\u2010microscopy and Crystallographic Data","volume":"29","author":"Casa\u00f1al","year":"2020","journal-title":"Protein Sci."},{"key":"10.1016\/j.ejmech.2026.118961_bib75","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1107\/S0907444909029436","article-title":"Electronic Ligand Builder and Optimization Workbench (eLBOW): a tool for ligand coordinate and restraint generation","volume":"65","author":"Moriarty","year":"2009","journal-title":"Acta Crystallogr. D. Biol. Crystallogr."},{"key":"10.1016\/j.ejmech.2026.118961_bib76","series-title":"Methods Mol. Biol.","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-0716-2643-6_2","article-title":"Purification of recombinant eukaryotic MAO A and MAO B utilizing the Pichia pastoris expression System","author":"Edmondson","year":"2023"},{"key":"10.1016\/j.ejmech.2026.118961_bib77","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-0716-2643-6_9","article-title":"Crystallization of human monoamine oxidase B","author":"Binda","year":"2023","journal-title":"Methods Mol. Biol."},{"key":"10.1016\/j.ejmech.2026.118961_bib78","unstructured":"G. Caroli, J., Cecchini, D., Forneris, F., Gottinger, A., Malatesta, M., Marchese, S., Massari, M., & Tjallinks, PROTEINS RELATED TO PATHOGENESIS OF DISEASES, VIRAL PROTEINS, CELL DIVISION, SIGNALLING AND CHROMATIN PROCESSES, (n.d.). https:\/\/doi.org\/10.15151\/ESRF-ES-1716079795."},{"key":"10.1016\/j.ejmech.2026.118961_bib79","article-title":"Software XDS for image rotation, recognition and crystal symmetry assignment","author":"Kabsch","year":"2010","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"10.1016\/j.ejmech.2026.118961_bib80","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1107\/S0907444994003112","article-title":"The CCP4 suite: programs for protein crystallography","volume":"50","year":"1994","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"10.1016\/j.ejmech.2026.118961_bib81","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of Coot","volume":"66","author":"Emsley","year":"2010","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"10.1016\/j.ejmech.2026.118961_bib82","doi-asserted-by":"crossref","DOI":"10.1107\/S2059798318000979","article-title":"Overview of refinement procedures within REFMAC 5: utilizing data from different sources","author":"Kovalevskiy","year":"2018","journal-title":"Acta Crystallogr. Sect. D Struct. Biol."},{"key":"10.1016\/j.ejmech.2026.118961_bib83","doi-asserted-by":"crossref","first-page":"69090","DOI":"10.1021\/acsami.5c18528","article-title":"Size-Controlled mesoporous silica nanoparticles via template nanoarchitectonics from a deferoxamine derivative for enhanced blood\u2013brain barrier permeability and neuroprotective chelation therapy","volume":"17","author":"Onrubia-M\u00e1rquez","year":"2025","journal-title":"ACS Appl. Mater. Interfaces"}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S022352342600406X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S022352342600406X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T06:19:55Z","timestamp":1783923595000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S022352342600406X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":83,"alternative-id":["S022352342600406X"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.118961","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Leveraging multitargeting BChE-MAO B inhibitors against microglia-related neuroinflammation: in vitro biological evaluation, structure-activity relationships, drug-like properties, and X-ray crystal complexes","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.118961","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Masson SAS.","name":"copyright","label":"Copyright"}],"article-number":"118961"}}