{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T22:01:47Z","timestamp":1784671307517,"version":"3.55.0"},"reference-count":131,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100012819","name":"Egyptian Cultural and Educational Bureau","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012819","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016982","name":"Yamagata University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016982","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":[[2026,5]]},"DOI":"10.1016\/j.ejmech.2026.118738","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T20:33:53Z","timestamp":1772483633000},"page":"118738","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Design and development of 1,5-diarylpyrazole-based multitarget-directed ligands as dual COX-2\/HDAC6 inhibitors for Alzheimer's disease therapy: Molecular dynamics and experimental insights"],"prefix":"10.1016","volume":"309","author":[{"given":"Kamal S.","family":"Abdelrahman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osama M.","family":"Soltan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hend E.","family":"Abo Mansour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amany E.","family":"Nofal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman A.","family":"Eissa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba Rady","family":"Salem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa M.","family":"Mahfouz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samar A.","family":"El-Adawy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada S.A.","family":"Ewies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelrahman","family":"Hamdi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostafa M.","family":"Elbadawi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed H.A.","family":"Abusabaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed A.","family":"El-Rashedy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6629-6102","authenticated-orcid":false,"given":"Hiroyuki","family":"Konno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr K.A.","family":"Bass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejmech.2026.118738_bib1","doi-asserted-by":"crossref","first-page":"S188","DOI":"10.37765\/ajmc.2022.89236","article-title":"The economic and societal burden of Alzheimer disease: managed care considerations","volume":"28","author":"Skaria","year":"2022","journal-title":"Am. J. Manag. Care"},{"key":"10.1016\/j.ejmech.2026.118738_bib2","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s41531-021-00213-7","article-title":"Genetic and environmental factors in Alzheimer's and Parkinson's diseases and promising therapeutic intervention via fecal microbiota transplantation","volume":"7","author":"Wang","year":"2021","journal-title":"Parkinsons Dis."},{"key":"10.1016\/j.ejmech.2026.118738_bib3","doi-asserted-by":"crossref","DOI":"10.1016\/j.arr.2024.102481","article-title":"Pathogenesis, diagnostics, and therapeutics for Alzheimer's disease: breaking the memory barrier","volume":"101","author":"Kamatham","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"10.1016\/j.ejmech.2026.118738_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.arr.2024.102556","article-title":"Epigenetic biomarkers in Alzheimer's disease: diagnostic and prognostic relevance","volume":"102","author":"Behl","year":"2024","journal-title":"Ageing Res. Rev."},{"key":"10.1016\/j.ejmech.2026.118738_bib5","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41580-021-00441-y","article-title":"Modulation of cellular processes by histone and non-histone protein acetylation","volume":"23","author":"Shvedunova","year":"2022","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.ejmech.2026.118738_bib6","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2024.107410","article-title":"Role of histone deacetylases and their inhibitors in neurological diseases","volume":"208","author":"Zhang","year":"2024","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.ejmech.2026.118738_bib7","doi-asserted-by":"crossref","DOI":"10.1155\/2011\/143269","article-title":"Targeting HDACs: a promising therapy for Alzheimer's disease","author":"Xu","year":"2011","journal-title":"Oxidative Med. Cell. Longevity 2011"},{"key":"10.1016\/j.ejmech.2026.118738_bib8","doi-asserted-by":"crossref","first-page":"537","DOI":"10.3389\/fphar.2020.00537","article-title":"Histone deacetylases inhibitors in neurodegenerative diseases, neuroprotection and neuronal differentiation","volume":"11","author":"Shukla","year":"2020","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.ejmech.2026.118738_bib9","doi-asserted-by":"crossref","first-page":"601","DOI":"10.4155\/fmc-2023-0336","article-title":"Design, synthesis and mechanistic study of new dual targeting HDAC\/tubulin inhibitors","volume":"16","author":"El-Zoghbi","year":"2024","journal-title":"Future Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118738_bib10","doi-asserted-by":"crossref","first-page":"158","DOI":"10.2174\/1570159X19666210609160017","article-title":"Understanding the role of histone deacetylase and their inhibitors in neurodegenerative disorders: current targets and future perspective","volume":"20","author":"Kumar","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"10.1016\/j.ejmech.2026.118738_bib11","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2024.112936","article-title":"Targeting STAT3 signaling pathway in the treatment of Alzheimer's disease with compounds from natural products","volume":"141","author":"Wen","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.ejmech.2026.118738_bib12","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.tips.2009.01.002","article-title":"The distinct roles of cyclooxygenase-1 and-2 in neuroinflammation: implications for translational research","volume":"30","author":"Choi","year":"2009","journal-title":"Trends Pharmacol. Sci."},{"key":"10.1016\/j.ejmech.2026.118738_bib13","doi-asserted-by":"crossref","DOI":"10.1016\/j.jsps.2023.101729","article-title":"Exploring the role of COX-2 in Alzheimer's disease: potential therapeutic implications of COX-2 inhibitors","author":"Moussa","year":"2023","journal-title":"Saudi Pharm. J."},{"key":"10.1016\/j.ejmech.2026.118738_bib14","doi-asserted-by":"crossref","first-page":"665","DOI":"10.2147\/CIA.S357558","article-title":"Neuroinflammation as a potential therapeutic target in Alzheimer's disease","author":"Liu","year":"2022","journal-title":"Clin. Interv. Aging"},{"key":"10.1016\/j.ejmech.2026.118738_bib15","doi-asserted-by":"crossref","first-page":"3016","DOI":"10.1021\/ja045558b","article-title":"\u03b2-Sheet ligands in action: KLVFF recognition by aminopyrazole hybrid receptors in water","volume":"127","author":"Rzepecki","year":"2005","journal-title":"J. Am. Chem. Soc."},{"key":"10.1016\/j.ejmech.2026.118738_bib16","article-title":"Design, synthesis, and biological evaluation of novel 1, 5-diarylpyrazole carboxamides with dual inhibition of EGFR and COX-2 for the treatment of cancer and inflammatory diseases","author":"Soltan","year":"2025","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2026.118738_bib17","doi-asserted-by":"crossref","first-page":"6521","DOI":"10.3390\/molecules28186521","article-title":"Development and assessment of 1, 5\u2013diarylpyrazole\/oxime hybrids targeting EGFR and JNK\u20132 as antiproliferative agents: a comprehensive study through synthesis, molecular docking, and evaluation","volume":"28","author":"Abdelrahman","year":"2023","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2026.118738_bib18","doi-asserted-by":"crossref","first-page":"8843","DOI":"10.1523\/JNEUROSCI.2868-05.2005","article-title":"Lipopolysaccharide-induced inflammation exacerbates tau pathology by a cyclin-dependent kinase 5-mediated pathway in a transgenic model of Alzheimer's disease","volume":"25","author":"Kitazawa","year":"2005","journal-title":"J. Neurosci."},{"key":"10.1016\/j.ejmech.2026.118738_bib19","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2024.107651","article-title":"Design of multi-target drugs of HDACs and other anti-alzheimer related targets: current strategies and future prospects in alzheimer's diseases therapy","volume":"151","author":"Soltan","year":"2024","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2026.118738_bib20","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1038\/nrd2111","article-title":"Untangling tau hyperphosphorylation in drug design for neurodegenerative diseases","volume":"6","author":"Mazanetz","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.ejmech.2026.118738_bib21","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1002\/med.20248","article-title":"Recent advances in the multitarget\u2010directed ligands approach for the treatment of Alzheimer's disease","volume":"33","author":"Leon","year":"2013","journal-title":"Med. Res. Rev."},{"key":"10.1016\/j.ejmech.2026.118738_bib22","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2022.837649","article-title":"Multi-targets: an unconventional drug development strategy for Alzheimer's disease","volume":"14","author":"Gong","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.ejmech.2026.118738_bib23","doi-asserted-by":"crossref","DOI":"10.1002\/ardp.70046","article-title":"Click chemistry\u2010aided synthesis of triazole\u2010tethered benzothiazoles as novel multifunctional agents against Alzheimer's disease","volume":"358","author":"Elbadawi","year":"2025","journal-title":"Arch. Pharm."},{"key":"10.1016\/j.ejmech.2026.118738_bib24","doi-asserted-by":"crossref","first-page":"3226","DOI":"10.1021\/acschemneuro.3c00358","article-title":"Design, synthesis, and proof of concept of balanced dual inhibitors of butyrylcholinesterase (BChE) and histone deacetylase 6 (HDAC6) for the treatment of Alzheimer's disease","volume":"14","author":"Wang","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"10.1016\/j.ejmech.2026.118738_bib25","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.1016\/j.biopha.2018.11.017","article-title":"ACY-1215 exhibits anti-inflammatory and chondroprotective effects in human osteoarthritis chondrocytes via inhibition of STAT3 and NF-\u03baB signaling pathways","volume":"109","author":"Cheng","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.ejmech.2026.118738_bib26","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2021.113768","article-title":"Molecular hybrids: a five-year survey on structures of multiple targeted hybrids of protein kinase inhibitors for cancer therapy","volume":"225","author":"Soltan","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118738_bib27","article-title":"Design, synthesis, and biological evaluation of novel 1, 5-diarylpyrazole carboxamides with dual inhibition of EGFR and COX-2 for the treatment of cancer and inflammatory diseases","author":"Soltan","year":"2025","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejmech.2026.118738_bib28","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1111\/febs.12079","article-title":"Histone deacetylase 6 plays a role as a distinct regulator of diverse cellular processes","volume":"280","author":"Li","year":"2013","journal-title":"FEBS J."},{"key":"10.1016\/j.ejmech.2026.118738_bib29","doi-asserted-by":"crossref","first-page":"226","DOI":"10.3389\/fncel.2015.00226","article-title":"Histone acetylation modifiers in the pathogenesis of Alzheimer's disease","volume":"9","author":"Lu","year":"2015","journal-title":"Front. Cell. Neurosci."},{"key":"10.1016\/j.ejmech.2026.118738_bib30","doi-asserted-by":"crossref","first-page":"4","DOI":"10.5812\/jjnpp.69143","article-title":"Ginkgo biloba extract decreases scopolamine-induced congophilic amyloid plaques accumulation in male rat's brain","volume":"13","author":"Nikmahzar","year":"2018","journal-title":"Jundishapur J. Nat. Pharm. Prod."},{"key":"10.1016\/j.ejmech.2026.118738_bib34","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1021\/jm00189a022","article-title":"Preparation and antidiabetic activity of some sulfonylurea derivatives of 3, 5-disubstituted pyrazoles","volume":"22","author":"Soliman","year":"1979","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118738_bib35","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1021\/acs.jmedchem.7b01845","article-title":"Discovery of 1, 5-diphenylpyrazole-3-carboxamide derivatives as potent, reversible, and selective monoacylglycerol lipase (MAGL) inhibitors","volume":"61","author":"Aghazadeh Tabrizi","year":"2018","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118738_bib36","doi-asserted-by":"crossref","DOI":"10.1002\/alz.060848","article-title":"Effects of histone deacetylase inhibitors on different memory domains in an animal model of aging and Alzheimer's disease","volume":"18","author":"McClarty","year":"2022","journal-title":"Alzheimer's Dementia"},{"key":"10.1016\/j.ejmech.2026.118738_bib37","doi-asserted-by":"crossref","first-page":"15248","DOI":"10.1523\/JNEUROSCI.6361-11.2013","article-title":"Cyclooxygenase-1-dependent prostaglandins mediate susceptibility to systemic inflammation-induced acute cognitive dysfunction","volume":"33","author":"Griffin","year":"2013","journal-title":"J. Neurosci."},{"key":"10.1016\/j.ejmech.2026.118738_bib38","doi-asserted-by":"crossref","first-page":"268","DOI":"10.4062\/biomolther.2024.110","article-title":"A novel histone deacetylase 6 inhibitor, 4-FHA, improves scopolamine-induced cognitive and memory impairment in mice","volume":"33","author":"Seo","year":"2025","journal-title":"Biomol. Therapeut."},{"key":"10.1016\/j.ejmech.2026.118738_bib39","doi-asserted-by":"crossref","DOI":"10.1096\/fj.202301762RR","article-title":"Histone deacetylase\u20103 regulates the expression of the amyloid precursor protein and its inhibition promotes neuroregenerative pathways in Alzheimer's disease models","volume":"38","author":"Davis","year":"2024","journal-title":"FASEB J."},{"key":"10.1016\/j.ejmech.2026.118738_bib40","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13024-025-00796-2","article-title":"Upregulated astrocyte HDAC7 induces alzheimer-like tau pathologies via deacetylating transcription factor-EB and inhibiting lysosome biogenesis","volume":"20","author":"Ye","year":"2025","journal-title":"Mol. Neurodegener."},{"key":"10.1016\/j.ejmech.2026.118738_bib41","doi-asserted-by":"crossref","first-page":"908","DOI":"10.2174\/1570159X18666201111104509","article-title":"Glia-driven neuroinflammation and systemic inflammation in Alzheimer's disease","volume":"19","author":"Hashioka","year":"2021","journal-title":"Curr. Neuropharmacol."},{"key":"10.1016\/j.ejmech.2026.118738_bib42","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1002\/alz.13450","article-title":"Astrocyte biomarkers GFAP and YKL\u201040 mediate early Alzheimer's disease progression","volume":"20","author":"Pelkmans","year":"2024","journal-title":"Alzheimer's Dementia"},{"key":"10.1016\/j.ejmech.2026.118738_bib43","doi-asserted-by":"crossref","first-page":"44","DOI":"10.21608\/jmals.2021.210630","article-title":"Celecoxib effect on rivastigmine anti-Alzheimer activity against aluminum chloride-induced neurobehavioral deficits as a rat model of Alzheimer's disease; novel perspectives for an old drug","volume":"3","author":"Abdel-Aal","year":"2021","journal-title":"J. Med. Life Sci."},{"key":"10.1016\/j.ejmech.2026.118738_bib32","doi-asserted-by":"crossref","DOI":"10.1124\/jpet.124.002170","article-title":"Central nervous system distributional kinetics of selected histone deacetylase inhibitors","volume":"392","author":"Zhang","year":"2025","journal-title":"J. Pharmacol. Exp. Therapeut."},{"key":"10.1016\/j.ejmech.2026.118738_bib44","article-title":"Association of region\u2010specific hippocampal reduction of neurogranin with inflammasome proteins in post mortem brains of Alzheimer's disease","volume":"10","author":"Vontell","year":"2024","journal-title":"Alzheimer's Dementia: Translational Res. Clinical Interventions"},{"key":"10.1016\/j.ejmech.2026.118738_bib45","article-title":"Novel HDAC11 inhibitors for Alzheimer's disease treatment in preclinical models","volume":"18","author":"Wang","year":"2022","journal-title":"Alzheimer's Dementia"},{"key":"10.1016\/j.ejmech.2026.118738_bib46","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.2174\/0929867329666220826163626","article-title":"Hybrid histone deacetylase inhibitor: an effective strategy for cancer therapy","volume":"30","author":"Wu","year":"2023","journal-title":"Curr. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118738_bib47","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/jnc.12059","article-title":"Cyclooxygenase\u20101 inhibition reduces amyloid pathology and improves memory deficits in a mouse model of Alzheimer's disease","volume":"124","author":"Choi","year":"2013","journal-title":"J. Neurochem."},{"key":"10.1016\/j.ejmech.2026.118738_bib48","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1111\/jnc.15342","article-title":"Advances in understanding meso\u2010cortico\u2010limbic\u2010striatal systems mediating risky reward seeking","volume":"157","author":"Piantadosi","year":"2021","journal-title":"J. Neurochem."},{"key":"10.1016\/j.ejmech.2026.118738_bib49","series-title":"In Synapse Pathology in Alzheimer's Disease, Seminars in Cell & Developmental Biology","first-page":"13","author":"Griffiths","year":"2023"},{"key":"10.1016\/j.ejmech.2026.118738_bib50","doi-asserted-by":"crossref","first-page":"2976","DOI":"10.1002\/jnr.24934","article-title":"Is cyclooxygenase\u20101 involved in neuroinflammation?","volume":"99","author":"Ghazanfari","year":"2021","journal-title":"J. Neurosci. Res."},{"key":"10.1016\/j.ejmech.2026.118738_bib51","doi-asserted-by":"crossref","first-page":"347","DOI":"10.3390\/genes14020347","article-title":"Histone modifications in Alzheimer's disease","volume":"14","author":"Santana","year":"2023","journal-title":"Genes"},{"key":"10.1016\/j.ejmech.2026.118738_bib52","doi-asserted-by":"crossref","DOI":"10.3389\/fnagi.2020.619866","article-title":"Class I HDAC inhibitor improves synaptic proteins and repairs cytoskeleton through regulating synapse-related genes in vitro and in vivo","volume":"12","author":"Han","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"10.1016\/j.ejmech.2026.118738_bib53","doi-asserted-by":"crossref","DOI":"10.1016\/j.jsps.2023.101729","article-title":"Exploring the role of COX-2 in Alzheimer's disease: potential therapeutic implications of COX-2 inhibitors","volume":"31","author":"Moussa","year":"2023","journal-title":"Saudi Pharm. J."},{"key":"10.1016\/j.ejmech.2026.118738_bib54","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/alzrt241","article-title":"Histone deacetylase 6 inhibition improves memory and reduces total tau levels in a mouse model of tau deposition","volume":"6","author":"Selenica","year":"2014","journal-title":"Alzheimers Res. Ther."},{"key":"10.1016\/j.ejmech.2026.118738_bib55","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/1742-2094-3-24","article-title":"Fibrillar beta-amyloid peptide A\u03b21\u201340 activates microglial proliferation via stimulating TNF-\u03b1 release and H2O2 derived from NADPH oxidase: a cell culture study","volume":"3","author":"Jekabsone","year":"2006","journal-title":"J. Neuroinflammation"},{"key":"10.1016\/j.ejmech.2026.118738_bib56","doi-asserted-by":"crossref","first-page":"742","DOI":"10.3390\/biomedicines10040742","article-title":"Addressing blood-brain barrier impairment in Alzheimer's disease","volume":"10","author":"Sharma","year":"2022","journal-title":"Biomedicines"},{"key":"10.1016\/j.ejmech.2026.118738_bib57","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1007\/s10787-021-00889-6","article-title":"Recent advances in molecular pathways and therapeutic implications targeting neuroinflammation for Alzheimer's disease","volume":"29","author":"Dhapola","year":"2021","journal-title":"Inflammopharmacology"},{"key":"10.1016\/j.ejmech.2026.118738_bib58","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.neuroscience.2017.12.046","article-title":"Celecoxib prevents cognitive impairment and neuroinflammation in soluble amyloid \u03b2-treated rats","volume":"372","author":"Mhillaj","year":"2018","journal-title":"Neuroscience"},{"key":"10.1016\/j.ejmech.2026.118738_bib59","doi-asserted-by":"crossref","first-page":"5803","DOI":"10.3390\/ijms25115803","article-title":"Roles of cytokines in Alzheimer's disease","volume":"25","author":"Chen","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejmech.2026.118738_bib60","doi-asserted-by":"crossref","DOI":"10.3389\/fphys.2022.814889","article-title":"The multifaceted neurotoxicity of astrocytes in ageing and age-related neurodegenerative diseases: a translational perspective","volume":"13","author":"Bouvier","year":"2022","journal-title":"Front. Physiol."},{"key":"10.1016\/j.ejmech.2026.118738_bib61","doi-asserted-by":"crossref","first-page":"6966","DOI":"10.1111\/jcmm.15358","article-title":"HDAC inhibitor protects chronic cerebral hypoperfusion and oxygen\u2010glucose deprivation injuries via H3K14 and H4K5 acetylation\u2010mediated BDNF expression","volume":"24","author":"Fang","year":"2020","journal-title":"J. Cell Mol. Med."},{"key":"10.1016\/j.ejmech.2026.118738_bib62","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.bbr.2010.01.040","article-title":"The role of TNF-\u03b1 signaling pathway on COX-2 upregulation and cognitive decline induced by \u03b2-amyloid peptide","volume":"209","author":"Medeiros","year":"2010","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.ejmech.2026.118738_bib63","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1248\/bpb.b21-00381","article-title":"Astragaloside IV ameliorates cognitive impairment and neuroinflammation in an oligomeric a\u03b2 induced Alzheimer's disease mouse model via inhibition of microglial activation and NADPH oxidase expression","volume":"44","author":"Chen","year":"2021","journal-title":"Biol. Pharm. Bull."},{"key":"10.1016\/j.ejmech.2026.118738_bib64","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2022.926914","article-title":"Crosstalk between acetylation and the tyrosination\/detyrosination cycle of \u03b1-tubulin in Alzheimer's disease","volume":"10","author":"Mart\u00ednez-Hern\u00e1ndez","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.ejmech.2026.118738_bib65","doi-asserted-by":"crossref","first-page":"606","DOI":"10.3390\/antiox13050606","article-title":"Role of epigenetic modulation in neurodegenerative diseases: implications of phytochemical interventions","volume":"13","author":"Prasanth","year":"2024","journal-title":"Antioxidants"},{"key":"10.1016\/j.ejmech.2026.118738_bib66","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.3233\/JAD-140066","article-title":"Tubastatin A\/ACY-1215 improves cognition in Alzheimer's disease transgenic mice","volume":"41","author":"Zhang","year":"2014","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"10.1016\/j.ejmech.2026.118738_bib67","series-title":"The Therapeutic Potential of Epigenetic Modifications in Alzheimer's Disease","first-page":"151","author":"Bufill","year":"2020"},{"key":"10.1016\/j.ejmech.2026.118738_bib68","doi-asserted-by":"crossref","first-page":"818","DOI":"10.3390\/antiox9090818","article-title":"Mitochondrial oxidative and nitrosative stress and Alzheimer disease","volume":"9","author":"Butterfield","year":"2020","journal-title":"Antioxidants"},{"key":"10.1016\/j.ejmech.2026.118738_bib69","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1080\/00207454.2022.2150190","article-title":"S-nitrosoglutathione modulates HDAC2 and BDNF levels in the brain and improves cognitive deficits in experimental model of Alzheimer's disease in rats","volume":"134","author":"Dubey","year":"2024","journal-title":"Int. J. Neurosci."},{"key":"10.1016\/j.ejmech.2026.118738_bib70","doi-asserted-by":"crossref","first-page":"5718","DOI":"10.1016\/j.bmc.2018.10.022","article-title":"Design, synthesis, and biological evaluation of histone deacetylase inhibitors possessing glutathione peroxidase-like and antioxidant activities against Alzheimer's disease","volume":"26","author":"Hu","year":"2018","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118738_bib71","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1038\/nm1362","article-title":"Prostaglandin E2 EP1 receptors: downstream effectors of COX-2 neurotoxicity","volume":"12","author":"Kawano","year":"2006","journal-title":"Nat. Med."},{"key":"10.1016\/j.ejmech.2026.118738_bib72","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1089\/ars.2006.8.1975","article-title":"Nitrosative stress, cellular stress response, and thiol homeostasis in patients with Alzheimer's disease","volume":"8","author":"Calabrese","year":"2006","journal-title":"Antioxidants Redox Signal."},{"key":"10.1016\/j.ejmech.2026.118738_bib33","doi-asserted-by":"crossref","first-page":"5560","DOI":"10.3390\/ijms23105560","article-title":"Improvement of cognitive function in ovariectomized rats by human neural stem cells overexpressing choline acetyltransferase via secretion of NGF and BDNF","volume":"23","author":"Yoon","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.ejmech.2026.118738_bib73","doi-asserted-by":"crossref","first-page":"5511","DOI":"10.7150\/thno.56541","article-title":"STAT3 ameliorates cognitive deficits via regulation of NMDAR expression in an Alzheimer's disease animal model","volume":"11","author":"Wan","year":"2021","journal-title":"Theranostics"},{"key":"10.1016\/j.ejmech.2026.118738_bib74","doi-asserted-by":"crossref","first-page":"6873","DOI":"10.1523\/JNEUROSCI.0519-10.2010","article-title":"Tyk2\/STAT3 signaling mediates \u03b2-amyloid-induced neuronal cell death: implications in Alzheimer's disease","volume":"30","author":"Wan","year":"2010","journal-title":"J. Neurosci."},{"key":"10.1016\/j.ejmech.2026.118738_bib75","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1159\/000450681","article-title":"Genome-wide STAT3 binding analysis after histone deacetylase inhibition reveals novel target genes in dendritic cells","volume":"9","author":"Sun","year":"2017","journal-title":"J. Innate Immun."},{"key":"10.1016\/j.ejmech.2026.118738_bib31","first-page":"15","article-title":"Naringenin protects against scopolamine-induced dementia in rats","volume":"52","author":"Zaki","year":"2014","journal-title":"Bull. Fac. Pharm. Cairo Univ."},{"key":"10.1016\/j.ejmech.2026.118738_bib76","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1007\/s10735-021-09998-6","article-title":"Histological and imunohistochemical alterations of hippocampus and prefrontal cortex in a rat model of Alzheimer like-disease with a preferential role of the flavonoid \u201chesperidin\u201d","volume":"52","author":"Mandour","year":"2021","journal-title":"J. Mol. Histol."},{"key":"10.1016\/j.ejmech.2026.118738_bib77","first-page":"256","article-title":"The pathophysiology of Alzheimer's disease and directions in treatment","volume":"3","author":"Morrison","year":"2005","journal-title":"Adv. Stud. Nurs."},{"key":"10.1016\/j.ejmech.2026.118738_bib78","doi-asserted-by":"crossref","DOI":"10.1016\/j.brainres.2024.148847","article-title":"Study on multi-target effects of the novel HDAC6 inhibitor W5 on A\u03b2\/Cu2+-induced Alzheimer's disease model of rats","volume":"1832","author":"Liu","year":"2024","journal-title":"Brain Res."},{"key":"10.1016\/j.ejmech.2026.118738_bib79","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1186\/s12974-018-1321-3","article-title":"The small molecule CA140 inhibits the neuroinflammatory response in wild-type mice and a mouse model of AD","volume":"15","author":"Lee","year":"2018","journal-title":"J. Neuroinflammation"},{"issue":"3","key":"10.1016\/j.ejmech.2026.118738_bib80","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1095\/biolreprod.104.039032","article-title":"Modulation of cytokine-induced cyclooxygenase 2 expression by PPARG ligands through NF\u03baB signal disruption in human WISH and amnion cells","volume":"73","author":"Ackerman","year":"2005","journal-title":"Biol. Reprod."},{"issue":"5","key":"10.1016\/j.ejmech.2026.118738_bib81","doi-asserted-by":"crossref","first-page":"449","DOI":"10.4168\/aair.2014.6.5.449","article-title":"Prostaglandin E2 induces IL-6 and IL-8 production by the EP receptors\/Akt\/NF-\u03baB pathways in nasal polyp-derived fibroblasts","volume":"6","author":"Cho","year":"2014","journal-title":"Allergy Asthma Immunol. Res."},{"issue":"6","key":"10.1016\/j.ejmech.2026.118738_bib82","article-title":"Prostaglandins E2 signal mediated by receptor subtype EP2 promotes IgE production in vivo and contributes to asthma development","volume":"8","author":"Gao","year":"2016","journal-title":"Sci. Rep."},{"issue":"11","key":"10.1016\/j.ejmech.2026.118738_bib83","doi-asserted-by":"crossref","first-page":"4433","DOI":"10.1158\/0008-5472.CAN-09-4289","article-title":"Persistent cyclooxygenase-2 inhibition downregulates NF-\u03baB, resulting in chronic intestinal inflammation in the min\/+ mouse model of colon tumorigenesis","volume":"70","author":"Carothers","year":"2010","journal-title":"Cancer Res."},{"issue":"1","key":"10.1016\/j.ejmech.2026.118738_bib84","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s12974-025-03400-y","article-title":"Inhibition of histone deacetylase 6 alleviates neuropathic pain via direct regulating post-translation of spinal STAT3 and decreasing downstream CC Motif Chemokine Ligand 7 synthesis","volume":"22","author":"Chi","year":"2025","journal-title":"J. Neuroinflammation"},{"issue":"9","key":"10.1016\/j.ejmech.2026.118738_bib85","doi-asserted-by":"crossref","first-page":"1924","DOI":"10.1016\/j.cellsig.2013.05.007","article-title":"Regulation of STAT signaling by acetylation","volume":"25","author":"Zhuang","year":"2013","journal-title":"Cell. Signal."},{"issue":"1","key":"10.1016\/j.ejmech.2026.118738_bib86","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cytogfr.2009.11.005","article-title":"Dangerous liaisons: STAT3 and NF-kappaB collaboration and crosstalk in cancer","volume":"21","author":"Grivennikov","year":"2010","journal-title":"Cytokine Growth Factor Rev."},{"key":"10.1016\/j.ejmech.2026.118738_bib87","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/j.biopha.2017.10.103","article-title":"Histone deacetylase 6 inhibitor ACY-1215 protects against experimental acute liver failure by regulating the TLR4-MAPK\/NF-\u03baB pathway","volume":"97","author":"Zhang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.ejmech.2026.118738_bib88","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2024.1320077","article-title":"Suppressor of cytokine signaling-3 expression and its regulation in relation to inflammation in chronic obstructive pulmonary disease","volume":"15","author":"Tin\u00e8","year":"2024","journal-title":"Front. Immunol."},{"key":"10.1016\/j.ejmech.2026.118738_bib89","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.3389\/fimmu.2019.01267","article-title":"IL-10\/STAT3\/SOCS3 axis is involved in the anti-inflammatory effect of benznidazole","volume":"10","author":"Cevey","year":"2019","journal-title":"Front. Immunol."},{"issue":"3","key":"10.1016\/j.ejmech.2026.118738_bib90","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.exphem.2012.10.012","article-title":"Histone deacetylases inhibitor sodium butyrate inhibits JAK2\/STAT signaling through upregulation of SOCS1 and SOCS3 mediated by HDAC8 inhibition in myeloproliferative neoplasms","volume":"41","author":"Gao","year":"2013","journal-title":"Exp. Hematol."},{"key":"10.1016\/j.ejmech.2026.118738_bib91","first-page":"37","article-title":"Molecular dynamics simulations: advances and applications","author":"Hospital","year":"2015","journal-title":"Adv. Appl. Bioinform. Chem."},{"key":"10.1016\/j.ejmech.2026.118738_bib92","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.1021\/acs.jcim.8b00462","article-title":"GPU-accelerated molecular dynamics and free energy methods in Amber18: performance enhancements and new features","volume":"58","author":"Lee","year":"2018","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejmech.2026.118738_bib93","doi-asserted-by":"crossref","DOI":"10.1016\/j.bioorg.2020.103711","article-title":"Design, synthesis and biological evaluation of novel 5, 6, 7-trimethoxy-N-aryl-2-styrylquinolin-4-amines as potential anticancer agents and tubulin polymerization inhibitors","volume":"98","author":"Mirzaei","year":"2020","journal-title":"Bioorg. Chem."},{"key":"10.1016\/j.ejmech.2026.118738_bib94","doi-asserted-by":"crossref","first-page":"8355","DOI":"10.1007\/s10570-021-04063-7","article-title":"Synthesis of novel heterocyclic compounds based on dialdehyde cellulose: characterization, antimicrobial, antitumor activity, molecular dynamics simulation and target identification","volume":"28","author":"Hasanin","year":"2021","journal-title":"Cellulose"},{"key":"10.1016\/j.ejmech.2026.118738_bib95","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0070681","article-title":"Molecular dynamics study of Zn (a\u03b2) and Zn (a\u03b2) 2","volume":"8","author":"Pan","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.ejmech.2026.118738_bib96","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1080\/15216540500138246","article-title":"Conservation of eubacterial replicases","volume":"57","author":"Wijffels","year":"2005","journal-title":"IUBMB Life"},{"key":"10.1016\/j.ejmech.2026.118738_bib97","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/0022-2836(84)90231-6","article-title":"Solvent accessible surface area and excluded volume in proteins: analytical equations for overlapping spheres and implications for the hydrophobic effect","volume":"178","author":"Richmond","year":"1984","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.ejmech.2026.118738_bib98","doi-asserted-by":"crossref","first-page":"2911","DOI":"10.1021\/acs.jcim.7b00564","article-title":"Relative binding free energy calculations in drug discovery: recent advances and practical considerations","volume":"57","author":"Cournia","year":"2017","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejmech.2026.118738_bib99","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/S1359-6446(04)03280-5","article-title":"Improving the decision-making process in the structural modification of drug candidates: enhancing metabolic stability","volume":"9","author":"Nassar","year":"2004","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.ejmech.2026.118738_bib100","doi-asserted-by":"crossref","first-page":"335","DOI":"10.2478\/acph-2014-0028","article-title":"Novel ethyl 1, 5-disubstituted-1H-pyrazole-3-carboxylates as a new class of antimicrobial agents","volume":"64","author":"Radwan","year":"2014","journal-title":"Acta Pharm."},{"key":"10.1016\/j.ejmech.2026.118738_bib101","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ejmech.2019.03.008","article-title":"Design, synthesis and evaluation of novel diaryl-1, 5-diazoles derivatives bearing morpholine as potent dual COX-2\/5-LOX inhibitors and antitumor agents","volume":"169","author":"Li","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118738_bib102","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1021\/jm960803q","article-title":"Synthesis and biological evaluation of the 1, 5-diarylpyrazole class of cyclooxygenase-2 inhibitors: identification of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1 H-pyrazol-1-yl] benzenesulfonamide (SC-58635, celecoxib)","volume":"40","author":"Penning","year":"1997","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118738_bib103","first-page":"214","article-title":"Design, synthesis, molecular docking and biological evaluation of novel 1, 5-diarylpyrazole-N, O-dimethyl hydroxamate derivatives as antiproliferative agents","volume":"4","author":"Hassan","year":"2021","journal-title":"J. Adv. Biomed.Pharm. Sci."},{"key":"10.1016\/j.ejmech.2026.118738_bib104","first-page":"152","article-title":"Design, synthesis, molecular modeling and biological evaluation of novel 1, 5-Diarylpyrazole carboxamide derivatives as antiproliferative agents","volume":"4","author":"Shoman","year":"2021","journal-title":"J. Adv. Biomed. Pharm. Sci."},{"key":"10.1016\/j.ejmech.2026.118738_bib105","doi-asserted-by":"crossref","first-page":"6195","DOI":"10.1021\/jm0407761","article-title":"New COX-2\/5-LOX inhibitors: apoptosis-inducing agents potentially useful in prostate cancer chemotherapy","volume":"47","author":"Pommery","year":"2004","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118738_bib107","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S0014-827X(03)00136-8","article-title":"4-Substituted 1, 5-diarylpyrazole, analogues of celecoxib: synthesis and preliminary evaluation of biological properties","volume":"58","author":"Menozzi","year":"2003","journal-title":"Il Farmaco"},{"key":"10.1016\/j.ejmech.2026.118738_bib106","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1021\/jm2001376","article-title":"Synthesis and structure\u2212activity relationship studies of urea-containing pyrazoles as dual inhibitors of cyclooxygenase-2 and soluble epoxide hydrolase","volume":"54","author":"Hwang","year":"2011","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118738_bib108","doi-asserted-by":"crossref","first-page":"6528","DOI":"10.1016\/j.bmc.2008.05.028","article-title":"Diazen-1-ium-1, 2-diolated nitric oxide donor ester prodrugs of 1-(4-methanesulfonylphenyl)-5-aryl-1H-pyrazol-3-carboxylic acids: synthesis, nitric oxide release studies and anti-inflammatory activities","volume":"16","author":"Abdellatif","year":"2008","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118738_bib109","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.bmc.2016.12.032","article-title":"Bifunctional conjugates with potent inhibitory activity towards cyclooxygenase and histone deacetylase","volume":"25","author":"Raji","year":"2017","journal-title":"Bioorg. Med. Chem."},{"key":"10.1016\/j.ejmech.2026.118738_bib110","first-page":"183","article-title":"Effects on bone metabolism of new therapeutic strategies with standard chemotherapy and biologic drugs","volume":"10","author":"Ciolli","year":"2014","journal-title":"Clin. Cases Min. Bone Metab."},{"key":"10.1016\/j.ejmech.2026.118738_bib111","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nchembio.313","article-title":"Chemical phylogenetics of histone deacetylases","volume":"6","author":"Bradner","year":"2010","journal-title":"Nat. Chem. Biol."},{"key":"10.1016\/j.ejmech.2026.118738_bib112","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.3390\/molecules22081374","article-title":"Pharmacological and toxicological screening of novel benzimidazole-morpholine derivatives as dual-acting inhibitors","volume":"22","author":"Can","year":"2017","journal-title":"Molecules"},{"key":"10.1016\/j.ejmech.2026.118738_bib113","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s10020-022-00564-8","article-title":"Chronotherapeutic neuroprotective effect of verapamil against lipopolysaccharide-induced neuroinflammation in mice through modulation of calcium-dependent genes","volume":"28","author":"Mosalam","year":"2022","journal-title":"Mol. Med."},{"key":"10.1016\/j.ejmech.2026.118738_bib114","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.hest.2020.09.001","article-title":"Behavioral tests in rodent models of stroke","volume":"1","author":"Ruan","year":"2020","journal-title":"Brain Hemorrhages"},{"key":"10.1016\/j.ejmech.2026.118738_bib115","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1111\/joa.12390","article-title":"Histological and histochemical methods, theory and practice","volume":"228","author":"Szunyogova","year":"2016","journal-title":"J. Anat."},{"key":"10.1016\/j.ejmech.2026.118738_bib116","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/nchembio.2134","article-title":"Histone deacetylase 6 structure and molecular basis of catalysis and inhibition","volume":"12","author":"Hai","year":"2016","journal-title":"Nature chem. Biol."},{"key":"10.1016\/j.ejmech.2026.118738_bib117","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1107\/S2053230X16014230","article-title":"Crystal structure of rofecoxib bound to human cyclooxygenase-2","volume":"72","author":"Orlando","year":"2016","journal-title":"Structural Biol. Crystallization Commun."},{"key":"10.1016\/j.ejmech.2026.118738_bib118","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1002\/prot.20660","article-title":"Very fast empirical prediction and rationalization of protein pKa values","volume":"61","author":"Li","year":"2005","journal-title":"Proteins: Struct., Funct., Bioinf."},{"key":"10.1016\/j.ejmech.2026.118738_bib119","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1021\/cen-09233-scitech1","article-title":"Reflections on chemdraw","volume":"92","author":"Halford","year":"2014","journal-title":"Chem. Eng. News"},{"key":"10.1016\/j.ejmech.2026.118738_bib120","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1758-2946-4-17","article-title":"Avogadro: an advanced semantic chemical editor, visualization, and analysis platform","volume":"4","author":"Hanwell","year":"2012","journal-title":"J. Cheminf."},{"key":"10.1016\/j.ejmech.2026.118738_bib121","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1758-2946-1-15","article-title":"Application of the PM6 semi-empirical method to modeling proteins enhances docking accuracy of AutoDock","volume":"1","author":"Bikadi","year":"2009","journal-title":"J. Cheminf."},{"key":"10.1016\/j.ejmech.2026.118738_bib122","series-title":"Using Autodock with Autodocktools: a Tutorial","author":"Huey","year":"2006"},{"key":"10.1016\/j.ejmech.2026.118738_bib123","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1002\/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B","article-title":"Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function","volume":"19","author":"Morris","year":"1998","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.ejmech.2026.118738_bib124","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jmgm.2005.12.005","article-title":"Automatic atom type and bond type perception in molecular mechanical calculations","volume":"25","author":"Wang","year":"2006","journal-title":"J. Mol. Graph. Model."},{"key":"10.1016\/j.ejmech.2026.118738_bib125","doi-asserted-by":"crossref","first-page":"3084","DOI":"10.1021\/ct400341p","article-title":"PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data","volume":"9","author":"Roe","year":"2013","journal-title":"J. Chem. Theor. Comput."},{"key":"10.1016\/j.ejmech.2026.118738_bib126","series-title":"Originpro 9.1: Scientific Data Analysis and Graphing Software Software Review","author":"Seifert","year":"2014"},{"key":"10.1016\/j.ejmech.2026.118738_bib127","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera\u2014A visualization system for exploratory research and analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.ejmech.2026.118738_bib128","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1021\/ar000033j","article-title":"Calculating structures and free energies of complex molecules: combining molecular mechanics and continuum models","volume":"33","author":"Kollman","year":"2000","journal-title":"Accounts Chem. Res."},{"key":"10.1016\/j.ejmech.2026.118738_bib129","doi-asserted-by":"crossref","first-page":"2626","DOI":"10.1021\/ci4002475","article-title":"MMGBSA as a tool to understand the binding affinities of filamin\u2013peptide interactions","volume":"53","author":"Ylilauri","year":"2013","journal-title":"J. Chem. Inf. Model."},{"key":"10.1016\/j.ejmech.2026.118738_bib130","first-page":"171","article-title":"MM-GB (PB) SA calculations of protein-ligand binding free energies","volume":"11","author":"Hayes","year":"2012","journal-title":"Mol. Dynamics-Studies Syn. Biol. Macromol."},{"key":"10.1016\/j.ejmech.2026.118738_bib131","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1021\/ci100275a","article-title":"Assessing the performance of the MM\/PBSA and MM\/GBSA methods. 1. The accuracy of binding free energy calculations based on molecular dynamics simulations","volume":"51","author":"Hou","year":"2011","journal-title":"J. Chem. Inf. Model."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523426001832?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523426001832?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T21:18:08Z","timestamp":1784668688000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523426001832"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":131,"alternative-id":["S0223523426001832"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.118738","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Design and development of 1,5-diarylpyrazole-based multitarget-directed ligands as dual COX-2\/HDAC6 inhibitors for Alzheimer's disease therapy: Molecular dynamics and experimental insights","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2026.118738","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118738"}}