{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:04:50Z","timestamp":1785330290464,"version":"3.55.0"},"reference-count":70,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Alzheimer's disease is a neurodegenerative disease with limited therapeutic options and is most prevalent in the elderly. According to the cholinergic hypothesis, disease progression can be mitigated by inhibiting acetylcholinesterase (AChE). Herein, a series of substituted indole amines\n                    <jats:bold>19\u201042<\/jats:bold>\n                    was designed, synthesized via a Chiron\u2010guided approach to generate structurally diverse 2,3\u2010diphenyl\u2010substituted indole derivatives, and characterized by UV\u2013vis, FT\u2010IR, NMR, and MS. In silico studies, such as molecular docking, molecular dynamics simulations, and ADMET analyses, were performed to evaluate binding interactions, stability, and drug\u2010likeness, followed by in vitro cholinesterase inhibition assays. The compounds exhibited moderate inhibitory activity, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values ranging from 4.28 to 12.70\u00a0\u00b5M. Among them, compound\n                    <jats:bold>25<\/jats:bold>\n                    showed the highest activity (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 4.28\u00a0\u00b5M), comparable to galantamine (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 4.71\u00a0\u00b5M). Docking studies revealed strong binding affinities for halogenated derivatives, particularly compound\n                    <jats:bold>27<\/jats:bold>\n                    (\u221211.93\u00a0kcal\/mol), while MD simulations confirmed a stable protein\u2010ligand complex. Structure\u2010activity relationships indicated that phenyl and halogen substitution patterns influence binding and activity; however, biological potency did not strictly correlate with docking scores. ADMET analysis indicated several limitations, including poor solubility and limited BBB permeability, suggesting that these compounds should be considered preliminary lead scaffolds for further optimization.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202503327","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T08:01:47Z","timestamp":1783670507000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis, and Evaluation of Halogenated Indoles Amines as Acetylcholinesterase Inhibitors: Integrated In\u2010Vitro and In\u2010Silico Approaches"],"prefix":"10.1002","volume":"23","author":[{"given":"Abdul Rauf","family":"Raza","sequence":"first","affiliation":[{"name":"Institute of Chemistry University of Sargodha  Sargodha Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sobia","family":"Tariq","sequence":"additional","affiliation":[{"name":"Institute of Chemistry University of Sargodha  Sargodha Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humaira Yasmeen","family":"Gondal","sequence":"additional","affiliation":[{"name":"Institute of Chemistry University of Sargodha  Sargodha Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghayoor Abbas","family":"Chotana","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Engineering Syed Baber Ali School of Science and Engineering Lahore University of Management Sciences (LUMS)  Lahore Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2901-7212","authenticated-orcid":false,"given":"Muhammad Fayyaz ur","family":"Rehman","sequence":"additional","affiliation":[{"name":"Institute of Chemistry University of Sargodha  Sargodha Pakistan"},{"name":"Central Research Lab University of Sargodha  Sargodha Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahzaib","family":"Akhter","sequence":"additional","affiliation":[{"name":"Institute of Chemistry University of Sargodha  Sargodha Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70235"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.25259\/JNRP_356_2023"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1041610203008676"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11756-023-01528-x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/1385272826666220914114544"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.3c00230"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-15733-2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.02.057"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2020.128308"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2015.08.011"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2017.06.007"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2018.05.004"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.10.038"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arabjc.2022.103756"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2010.09.006"},{"key":"e_1_2_9_17_1","first-page":"20","article-title":"Synthesis, Characterization, Antidepressant Activity and Docking Studies of Some Novel Indole Bearing Azetidinone Derivatives","volume":"18","author":"Kerzare D. 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