{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:01:14Z","timestamp":1790776874266,"version":"4.1.0"},"reference-count":26,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,21]],"date-time":"2026-06-21T00:00:00Z","timestamp":1782000000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline associated with cholinergic dysfunction. Herein, we have designed and synthesized series of 4\u2010(naphthalen\u20101\u2010yl)\u22124\n                    <jats:italic>H<\/jats:italic>\n                    \u2010chromene derivatives\n                    <jats:bold>4<\/jats:bold>\n                    (\n                    <jats:bold>a\u2010n<\/jats:bold>\n                    ) by a one\u2010pot three\u2010component reaction with adequate synthetic yield and purity. Naphthalene\u2010chromene hybrids were synthesized by formation of two C\u2500C bonds and one C\u2500O bond in a single synthetic step. All synthesized compounds were tested for safety and efficacy using in vitro and in vivo studies. Compounds were found devoid of cytotoxicity in BV\u20102 cells. Most of the synthesized compounds have shown moderate to good inhibitory activity against cholinesterase enzymes. These compounds were found to be more selective towards acetylcholinesterase (AChE) compared to butyrylcholinesterase (BuChE). Compound\n                    <jats:bold>4\u2009m<\/jats:bold>\n                    has shown highest inhibitory potency against AChE (AChE, IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20091.08\u2009\u00b5M; BuChE, IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200982.59\u2009\u00b5M). The prototype compound (\n                    <jats:bold>4\u2009m<\/jats:bold>\n                    ) from in\u2010vitro screening was found to be safe in acute oral toxicity followed by histopathological analysis. Compound\n                    <jats:bold>4\u2009m<\/jats:bold>\n                    was evaluated for in vivo efficacy in scopolamine\u2010induced cognitive impairment model in mice. It significantly reversed the cognitive deficit in neurobehavioral tests. Pre\u2010treatment with\n                    <jats:bold>4\u2009m<\/jats:bold>\n                    have balanced key biochemical markers involved in the oxidative stress and cognitive functions. The compound\n                    <jats:bold>4\u2009m<\/jats:bold>\n                    alleviated neuronal tissue damage caused by scopolamine as indicated in the histological study. Molecular docking analysis also reconfirmed the binding affinity of\n                    <jats:bold>4\u2009m<\/jats:bold>\n                    at cholinesterase enzymes. Taken together, these findings supported the emergence of\n                    <jats:bold>4\u2009m<\/jats:bold>\n                    as a potential cholinesterase inhibitor for the treatment of AD.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70338","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T06:25:29Z","timestamp":1782109529000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Naphthalene\u20104\n                    <i>H<\/i>\n                    \u2010Chromene Molecular Hybrids as Dual Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6157-6295","authenticated-orcid":false,"given":"Vinod","family":"Ugale","sequence":"first","affiliation":[{"name":"R. C. Patel Institute of Pharmaceutical Education and Research Shirpur India"},{"name":"Bioprospecting Group, Agharkar Research Institute Savitribai Phule Pune University Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nissi","family":"Sharon","sequence":"additional","affiliation":[{"name":"Department of Chemistry, School of Science Gitam Deemed to be University Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandradip","family":"Salunkhe","sequence":"additional","affiliation":[{"name":"R. C. Patel Institute of Pharmaceutical Education and Research Shirpur India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jotiram","family":"Salunkhe","sequence":"additional","affiliation":[{"name":"R. C. Patel Institute of Pharmaceutical Education and Research Shirpur India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Lokwani","sequence":"additional","affiliation":[{"name":"Rajarshi Shahu College of Pharmacy Buldana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2397-4687","authenticated-orcid":false,"given":"Kalpesh","family":"Patil","sequence":"additional","affiliation":[{"name":"R. C. Patel Institute of Pharmaceutical Education and Research Shirpur India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9555-5572","authenticated-orcid":false,"given":"Pedavenkatagari Narayana","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Chemistry, School of Science Gitam Deemed to be University Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasad","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Bioprospecting Group, Agharkar Research Institute Savitribai Phule Pune University Pune India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,21]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10339-011-0430-z"},{"issue":"3","key":"e_1_2_8_3_1","first-page":"120","article-title":"Evaluation of Acute Oral Toxicity as Per OECD Guideline 425: A Study Report","volume":"9","author":"Chaudhary M.","year":"2019","journal-title":"Journal of Applied Pharmaceutical Science"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trci.2019.05.008"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1037\/h0045446"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(61)90145-9"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0306430"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(21)00249-8"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1022869222652"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-021-01249-0"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.14573\/altex.2009.2.83"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-024-03696-4"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2014.09.004"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2026.145762"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0149-7634(01)00041-0"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddtec.2004.11.007"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2025.142862"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.9b00207"},{"key":"e_1_2_8_19_1","unstructured":"QikProp. Schr\u00f6dinger Release2025\u22123 Schr\u00f6dinger LLC New York NY 2025."},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.70249"},{"key":"e_1_2_8_21_1","volume-title":"Protein Preparation Wizard; Epik, Impact, Prime","author":"Schr\u00f6dinger L. L. C.","year":"2021"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11030-024-10859-z"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2025.119622"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2022.02.002"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1678899"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.176028"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.116"}],"container-title":["Drug Development Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.70338","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ddr.70338","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.70338","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:35:42Z","timestamp":1790775342000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/ddr.70338"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,21]]},"references-count":26,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/ddr.70338"],"URL":"https:\/\/doi.org\/10.1002\/ddr.70338","archive":["Portico"],"relation":{},"ISSN":["0272-4391","1098-2299"],"issn-type":[{"value":"0272-4391","type":"print"},{"value":"1098-2299","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,21]]},"assertion":[{"value":"2026-04-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70338"}}