{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:16:28Z","timestamp":1790190988847,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Alzheimer's disease (AD) is a progressive neurodegenerative disorder that leads to gradual deterioration of cognitive functions. Cholinesterase enzymes play a critical role in regulating acetylcholine levels in the brain, and their dysfunction leads to impaired cholinergic neurotransmission, which is a primary hallmark of AD and contributes significantly to the cognitive decline and dementia. Here, a series of pyrazine\u20101,2,3\u2010triazole molecular hybrids incorporating a trifluoromethyl (\u2010CF\n                    <jats:sub>3<\/jats:sub>\n                    ) group were synthesized (\n                    <jats:bold>8a\u2013o<\/jats:bold>\n                    ). Synthesized compounds were then evaluated in vitro for cytotoxicity and cholinesterase inhibitory activities. All synthesized compounds were found to be nontoxic toward BV\u20102 cells in the cytotoxicity screening. The in vitro inhibition assays revealed that these derivatives exhibited greater inhibitory potency against acetylcholinesterase (AChE) than butyrylcholinesterase (BuChE). Among them, compound\n                    <jats:bold>8h<\/jats:bold>\n                    demonstrated the most potent AChE inhibition compared to BuChE (\n                    <jats:bold>AChE, IC<\/jats:bold>\n                    <jats:sub>\n                      <jats:bold>50<\/jats:bold>\n                    <\/jats:sub>\n                    \u2009=\u2009\n                    <jats:bold>5.43\u2009\u00b5M; BuChE, IC<\/jats:bold>\n                    <jats:sub>\n                      <jats:bold>50<\/jats:bold>\n                    <\/jats:sub>\n                    \u2009=\u2009\n                    <jats:bold>127.12\u2009\u00b5M<\/jats:bold>\n                    ). The most active compound\n                    <jats:bold>8h<\/jats:bold>\n                    was further subjected to molecular docking and dynamic simulation (100\u2009ns) to investigate its binding affinity, thermodynamic behavior, and stability within the active site of cholinesterase enzymes. Overall, the findings suggested that the synthesized compounds represent promising drug candidates as selective acetylcholinesterase inhibitors for the treatment of AD.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70249","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T13:53:27Z","timestamp":1770990807000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Structural Exploration of Pyrazine\u20101,2,3\u2010Triazole Hybrids as Selective Acetylcholinesterase Inhibitors for the Treatment of Alzheimer's Disease"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3723-6381","authenticated-orcid":false,"given":"Madala","family":"Ramesh","sequence":"first","affiliation":[{"name":"Department of Chemistry School of Science GITAM Deemed to be University Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5081-3278","authenticated-orcid":false,"given":"Pannala","family":"Padmaja","sequence":"additional","affiliation":[{"name":"Centre for Semio Chemicals, CSIR\u2010Indian Institute of Chemical Technology Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6157-6295","authenticated-orcid":false,"given":"Vinod","family":"Ugale","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry R. C. Patel Institute of Pharmaceutical Education and Research Shirpur Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6508-4183","authenticated-orcid":false,"given":"Atul","family":"Shirkhedkar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry R. C. Patel Institute of Pharmaceutical Education and Research Shirpur Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1124-6247","authenticated-orcid":false,"given":"Rahul","family":"Pawara","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry R. C. Patel Institute of Pharmacy Shirpur Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2858-678X","authenticated-orcid":false,"given":"Deepak","family":"Lokwani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Rajarshi Shahu College of Pharmacy Buldana Maharashtra India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0838-7823","authenticated-orcid":false,"given":"Srinivas","family":"Manda","sequence":"additional","affiliation":[{"name":"Department of Chemistry School of Science GITAM Deemed to be University Hyderabad 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"}]}],"member":"311","published-online":{"date-parts":[[2026,2,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X14666160325121145"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2021.131085"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22006"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01583"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28227495"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.201601638"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2018.06.005"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115253"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/14786419.2023.2241155"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/ml400304w"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm300871x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201900622"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2024.2322990"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2017.01.010"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.btre.2014.10.007"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtusci.2015.06.008"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.3184\/174751917X14836231670980"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2023.135354"},{"key":"e_1_2_10_20_1","first-page":"745","article-title":"A Computational Study of Cytotoxicity of Substituted Amides of Pyrazine\u20102\u2010Carboxylic Acids Using QSAR and DFT Based Molecular Surfaceelectrostatic Potential","volume":"12","author":"Hosseini S.","year":"2013","journal-title":"Iranian Journal of Pharmaceutical Research"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026619666190619115735"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules17078312"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2016.07.017"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01129"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.03.062"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2025.142862"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.103753"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/728983"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2006.11.009"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.12609"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2015.01.044"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20130013"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2018.10.056"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.procbio.2022.06.009"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2022.07.178"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450123666220328153741"},{"key":"e_1_2_10_38_1","unstructured":"QikProp version 4.4. 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