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Compounds 9 and 10 produced strong BaX gene downregulation (75.1% and 79.7%) and Bcl-2 upregulation, reduced AChE activity (70.2% and 75%), and elevated Wnt3a and β-catenin versus donepezil. They also suppressed GSK3β expression (77.1% and 78.7%). AChE inhibition was broad, while selectivity toward BChE varied. ADMET in silico and molecular docking supported the design, with some compounds showing higher BChE selectivity (SI \u003C 1).",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/from-bench-to-brain-novel-thieno-oxazine-hybrids-as-potent-pleiotropic-anti-alzheimers-agents-with-in-vivoin-vitro-validation-and-in-silico-insights/449441/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/from-bench-to-brain-novel-thieno-oxazine-hybrids-as-potent-pleiotropic-anti-alzheimers-agents-with-in-vivoin-vitro-validation-and-in-silico-insights/449441.png","ImageObject",300,407,{"name":92,"@type":93},"Muffet","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What compounds were synthesized and what starting material was used?","Question",{"text":112,"@type":113},"A novel series of thieno-oxazine hybrids (9–14) was synthesized starting from cyclohexa[b]thiophene.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did compounds 9 and 10 affect gene expression related to apoptosis?",{"text":117,"@type":113},"Compounds 9 and 10 showed the strongest BaX downregulation (75.1% and 79.7%) and Bcl-2 gene upregulation (about 8.1-fold for Bcl-2).",{"name":119,"@type":110,"acceptedAnswer":120},"What in vitro/in vivo and in silico approaches were used to evaluate activity?",{"text":121,"@type":113},"The work reports biological validation alongside enzyme effects, and it also includes in silico ADMET calculations and molecular docking for the synthesized compounds.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},449441,1791937581,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145,"preview_page_count":4},962090768927,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","ReseaRch aRticle    \nFrom bench to brain: novel thieno-oxazine hybrids as potent pleiotropic anti-Alzheimer’s agents with in vivo/in vitro validation and in silico insights  \neman a. Fayeda, Mazin a. a. Najmb, Khulood h. Oudahb, Maha a. ebrahima, Nirvana a.  \nGoharc, Karema abu-elfotuhd,e, ehsan Khedre Mohamedf, ahmed M. e. hamdang,h, Najla a. albalawii, shahad Faisal alzahranii, amira M. hamdanj, Reema almotairih,k, shaimaa M. hafezl and triveena M. Ramsism  \nadepartment of Pharmaceutical organic chemistry, faculty of Pharmacy (Girls), al-azhar university, cairo, Egypt; bdepartment of Pharmacy, mazaya university college, nasiriyah, Iraq; cdepartment of Pharmaceutical organic chemistry, faculty of Pharmacy, modern university for technology and Information (mtI), cairo, Egypt; ddepartment of clinical Pharmacy, faculty of Pharmacy (Girls), al-azhar university, cairo, Egypt; ecollege of Pharmacy, al-ayen Iraqi university, thi-Qar, Iraq; fdepartment of biochemistry, Egyptian drug authority (Eda), formerly national organization of drug control and research (nodcar), Giza, Egypt; gdepartment of Pharmacology and toxicology, faculty of Pharmacy, university of tabuk, tabuk, saudi arabia; hPrince fahad bin sultan chair for biomedical research (Pfscbr), university of tabuk, tabuk, saudi arabia; ifaculty of Pharmacy, university of tabuk, tabuk, saudi arabia; joceanography department, faculty of science, alexandria university, alexandria, Egypt; kdepartment of medical laboratory technology, faculty of applied medical sciences, university of tabuk, tabuk, saudi arabia; ldepartment of anatomy and Embryology, faculty of medicine, al-azhar university, cairo, Egypt; mdepartment of Pharmaceutical chemistry, faculty of Pharmacy, sinai university, Ismailia, Egypt  \nABSTRACT  \nDue to their various pharmacological effects, several substituted sulphur heterocycles containing thiophene have recently attracted a great deal of attention. a novel 2,3-diaryl-2,3,5,6,7,8-hexahydro-4H-benzo[4,5]thieno[3,2-e][1,3]oxazin-4-one (9–14) was synthesised starting from cyclohexa[b]thiophene. compounds 9 and 10 showed the greatest gene expression downregulation of BaX by 75.1% and 79.7%, and upregulation of Bcl-2 gene expression by 8.1 folds for [each. it](each. it) also decreased the level of ache by 70.2 and 75%; respectively. compounds 9 and 10 significantly increased Wnt3a levels by 5.8 and 6.6 folds, and β-catenin levels by 10.1 and 10.5 folds, respectively, compared to donepezil. they significantly downregulated 5-GsK3β gene expression by 77.1%, and 78.7%, respectively. even though all compounds exhibited potent inhibition of ache, all synthesised compounds, except for compounds 5 and 11 demonstrated higher selectivity towards Bche (si \u003C 1). In-silico aDMet calculations as well as molecular docking have been performed for synthetic compounds.  \nGRAPHICAL ABSTRACT  \nARTICLE HISTORY  \nReceived 18 July 2025 Revised 3 November 2025  \naccepted 28 November 2025  \nKEYWORDS  \nthieno-oxazines; alzheimer’s disease; ache and Bche inhibitors; aDMet and docking studies; multi-targets and histopathological examinations  \nCONTACT Eman a. fayed  [alfayed_e@azhar.edu.eg](alfayed_e@azhar.edu.eg); [alfayed_e@yahoo.com](alfayed_e@yahoo.com)  department of Pharmaceutical organic chemistry, faculty  \nof Pharmacy (Girls), al-azhar university, cairo, Egypt  \n supplemental data for this article can be accessed online at [https://doi.org/10.1080/14756366.2025.2598741](https://doi.org/10.1080/14756366.2025.2598741) .  \n© 2025 the author(s) . Published by Informa uK limited, trading as taylor & francis Group.  \nthis is an open access article distributed under the terms of the creative commons attribution-noncommercial license ([http://creativecommons.org/licenses/](http://creativecommons.org/licenses/)[ ](http://creativecommons.org/licenses/)[by-nc/4.0/](by-nc/4.0/)), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work i","cbCaiuWVD89Ep4uW","https://ap.wps.com/l/cbCaiuWVD89Ep4uW","pdf",7580034,41,"English","# Abstract\n## Introduction\n## Article history and key information\n## Graphical abstract and keywords\n## Contact and supplemental data","[{\"question\":\"What compounds were synthesized and what starting material was used?\",\"answer\":\"A novel series of thieno-oxazine hybrids (9–14) was synthesized starting from cyclohexa[b]thiophene.\"},{\"question\":\"How did compounds 9 and 10 affect gene expression related to apoptosis?\",\"answer\":\"Compounds 9 and 10 showed the strongest BaX downregulation (75.1% and 79.7%) and Bcl-2 gene upregulation (about 8.1-fold for Bcl-2).\"},{\"question\":\"What in vitro/in vivo and in silico approaches were used to evaluate activity?\",\"answer\":\"The work reports biological validation alongside enzyme effects, and it also includes in silico ADMET calculations and molecular docking for the synthesized compounds.\"}]","From bench to brain: novel thieno-oxazine hybrids as potent pleiotropic anti-Alzheimer’s agents with in vivo/in vitro validation and in silico insights | PDF",1790730221,103]