{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T12:00:18Z","timestamp":1775908818847,"version":"3.50.1"},"reference-count":117,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,17]],"date-time":"2025-08-17T00:00:00Z","timestamp":1755388800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research, Development, and Innovation Authority (RDIA), Saudi Arabia, Riyadh, Reactivating and Rebuilding of Existing Labs Initiative","award":["13262-Tabuk-2023-UT-R-3-1-HW-"],"award-info":[{"award-number":["13262-Tabuk-2023-UT-R-3-1-HW-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Alzheimer\u2019s disease (AD) is largely linked with oxidative stress, the accumulation of amyloid-\u03b2 plaques, and hyperphosphorylated \u03c4-protein aggregation. Alterations in dopaminergic and serotonergic neurotransmission have also been implicated in various AD-related symptoms. Methods: To explore new therapeutic agents, a series of bicyclic and tricyclic thieno-oxazepine derivatives were synthesized as potential acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The resultant compounds were purified via HPLC and characterized using spectral analysis techniques. Histopathological examinations, other antioxidants, and anti-inflammatory biomarkers were evaluated, and in silico ADMET calculations were performed for synthetic hybrids. Molecular docking was utilized to validate the new drugs\u2019 binding mechanisms. Results: The most powerful AChE inhibitors were 14 and 16, with respective values of IC50 equal to 0.39 and 0.76 \u00b5M. Derivative 15 demonstrated remarkable BChE-inhibitory efficacy, on par with tacrine, with IC50 values of 0.70 \u00b5M. Hybrids 13 and 15 showed greater selectivity towards BChE, despite substantial inhibition of AChE. Compounds 13 and 15 reduced escape latency and raised residence time, with almost equal activity to donepezil. Conclusions: According to these findings, the designed hybrids constitute multipotent lead compounds that could be used in the creation of novel anti-AD medications.<\/jats:p>","DOI":"10.3390\/ph18081214","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T07:53:12Z","timestamp":1755503592000},"page":"1214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Unlocking Therapeutic Potential of Novel Thieno-Oxazepine Hybrids as Multi-Target Inhibitors of AChE\/BChE and Evaluation Against Alzheimer\u2019s Disease: In Vivo, In Vitro, Histopathological, and Docking Studies"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5014-7129","authenticated-orcid":false,"given":"Khulood H.","family":"Oudah","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Mazaya University College, Nasiriyah 64001, Iraq"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mazin A. A.","family":"Najm","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Mazaya University College, Nasiriyah 64001, Iraq"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2485-5479","authenticated-orcid":false,"given":"Triveena M.","family":"Ramsis","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sinai University, Kantara Branch, Ismailia 41636, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5877-0671","authenticated-orcid":false,"given":"Maha A.","family":"Ebrahim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6442-7762","authenticated-orcid":false,"given":"Nirvana A.","family":"Gohar","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Cairo 11571, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karema","family":"Abu-Elfotuh","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, Egypt"},{"name":"College of Pharmacy, Al-Ayen Iraqi University (AUIQ), An Nasiriyah 64004, Iraq"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4956-1522","authenticated-orcid":false,"given":"Ehsan Khedre","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Egyptian Drug Authority (EDA), Formerly National Organization of Drug Control and Research (NODCAR), Giza 12654, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4930-792X","authenticated-orcid":false,"given":"Ahmed M. E.","family":"Hamdan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amira M.","family":"Hamdan","sequence":"additional","affiliation":[{"name":"Oceanography Department, Faculty of Science, Alexandria University, Alexandria 21515, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1432-460X","authenticated-orcid":false,"given":"Reema","family":"Almotairi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9825-0694","authenticated-orcid":false,"given":"Shaimaa R.","family":"Abdelmohsen","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, Faculty of Medicine, Al-Azhar University, Cairo 11754, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khaled Ragab","family":"Abdelhakim","sequence":"additional","affiliation":[{"name":"Department of Histology, Misr University for Science and Technology, Giza 12566, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9304-5309","authenticated-orcid":false,"given":"Abdou Mohammed Ahmed","family":"Elsharkawy","sequence":"additional","affiliation":[{"name":"Anatomy Department, Faculty of Medicine, Al-Azhar University, Cairo 11754, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4579-5180","authenticated-orcid":false,"given":"Eman A.","family":"Fayed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo 11754, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"543","DOI":"10.4103\/1673-5374.320970","article-title":"Pathological mechanisms and therapeutic strategies for Alzheimer\u2019s disease","volume":"17","author":"Ju","year":"2022","journal-title":"Neural Regen. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s13311-021-01172-w","article-title":"Emotional and Neuropsychiatric Disorders Associated with Alzheimer\u2019s Disease","volume":"19","author":"Heilman","year":"2022","journal-title":"Neurotherapeutics"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1021\/ml300058m","article-title":"The \u03b2-Amyloid Hypothesis in Alzheimer\u2019s Disease: Seeing Is Believing","volume":"3","author":"Kung","year":"2012","journal-title":"ACS Med. Chem. Lett."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/nrn2194","article-title":"Tau-mediated neurodegeneration in Alzheimer\u2019s disease and related disorders","volume":"8","author":"Ballatore","year":"2007","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"88","DOI":"10.4161\/cam.3.1.7402","article-title":"Oxidative stress in Alzheimer disease","volume":"3","author":"Gella","year":"2009","journal-title":"Cell Adh. Migr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4137","DOI":"10.1111\/j.1582-4934.2009.00892.x","article-title":"Mitochondrial accumulation of APP and A\u03b2: Significance for Alzheimer disease pathogenesis","volume":"13","author":"Pavlov","year":"2009","journal-title":"J. Cell. Mol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1093\/brain\/awy132","article-title":"The cholinergic system in the pathophysiology and treatment of Alzheimer\u2019s disease","volume":"141","author":"Hampel","year":"2018","journal-title":"Brain"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1111\/jnc.14052","article-title":"Cholinergic modulation of the hippocampal region and memory function","volume":"142","author":"Haam","year":"2017","journal-title":"J. Neurochem."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Shoaib, M., and Wallace, T.L. (2020). A Review of the Cholinergic System and Therapeutic Approaches to Treat Brain Disorders. Behavioral Pharmacology of the Cholinergic System, Springer International Publishing.","DOI":"10.1007\/978-3-030-56013-3"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"101","DOI":"10.2174\/1570159X13666150716165726","article-title":"Alzheimer\u2019s disease: Targeting the Cholinergic System","volume":"14","author":"Guimaraes","year":"2016","journal-title":"Curr. Neuropharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1080\/17425255.2021.1931681","article-title":"Does the application of acetylcholinesterase inhibitors in the treatment of Alzheimer\u2019s disease lead to depression?","volume":"17","year":"2021","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yang, Z., Zou, Y., and Wang, L. (2023). Neurotransmitters in Prevention and Treatment of Alzheimer\u2019s Disease. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043841"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3030","DOI":"10.1002\/anie.200802808","article-title":"Alzheimer\u2019s Disease: From Pathology to Therapeutic Approaches","volume":"48","author":"Jacobsen","year":"2009","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2174\/1570159X11311030006","article-title":"Acetylcholinesterase Inhibitors: Pharmacology and Toxicology","volume":"11","author":"Colovic","year":"2013","journal-title":"Curr. Neuropharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1007\/s00441-006-0239-8","article-title":"Termination and beyond: Acetylcholinesterase as a modulator of synaptic transmission","volume":"326","author":"Zimmerman","year":"2006","journal-title":"Cell Tissue Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Walczak-Nowicka, \u0141.J., and Herbet, M. (2021). Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179290"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.2174\/1389557517666170120153930","article-title":"Acetylcholinesterase: A Primary Target for Drugs and Insecticides","volume":"17","author":"Thapa","year":"2017","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"703","DOI":"10.2174\/1389557520666200103100521","article-title":"Potent Acetylcholinesterase Inhibitors: Potential Drugs for Alzheimer\u2019s Disease","volume":"20","year":"2020","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3233\/NUA-2012-0006","article-title":"Polyphenols as acetylcholinesterase inhibitors: Structural specificity and impact on human disease","volume":"1","author":"Roseiro","year":"2012","journal-title":"Nutr. Aging"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/S0006-8993(97)01202-X","article-title":"Alteration of proteins regulating apoptosis, Bcl-2, Bcl-x, Bax, Bak, Bad, ICH-1 and CPP32, in Alzheimer\u2019s disease","volume":"780","author":"Kitamura","year":"1998","journal-title":"Brain Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1586\/17474086.2015.1026321","article-title":"Therapeutic targeting of Bcl-2 family for treatment of B-cell malignancies","volume":"8","author":"Huang","year":"2015","journal-title":"Expert Rev. Hematol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1038\/cdd.2015.50","article-title":"The BCL-2 protein family, BH3-mimetics and cancer therapy","volume":"22","author":"Delbridge","year":"2015","journal-title":"Cell Death Differ."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1517\/14728222.2013.733001","article-title":"Targeting the Bcl-2 family for cancer therapy","volume":"17","author":"Thomas","year":"2013","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13000-019-0841-1","article-title":"BCL2 overexpression: Clinical implication and biological insights in acute myeloid leukemia","volume":"14","author":"Zhou","year":"2019","journal-title":"Diagn. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.bbrc.2006.01.137","article-title":"Alzheimer\u2019s amyloid \u03b2-peptide (1\u201342) induces cell death in human neuroblastoma via bax\/bcl-2 ratio increase: An intriguing role for methionine 35","volume":"342","author":"Clementi","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"723","DOI":"10.3233\/JAD-161136","article-title":"PCSK9 Promotes oxLDL-Induced PC12 Cell Apoptosis Through the Bcl-2\/Bax-Caspase 9\/3 Signaling Pathway","volume":"57","author":"Liu","year":"2017","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.brainresbull.2018.01.006","article-title":"The effects of melatonin and curcumin on the expression of SIRT2, Bcl-2 and Bax in the hippocampus of adult rats","volume":"137","author":"Akbulut","year":"2018","journal-title":"Brain Res. Bull."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1007\/s00210-020-01863-9","article-title":"The potential chemotherapeutic effect of \u03b2-ionone and\/or sorafenib against hepatocellular carcinoma via its antioxidant effect, PPAR-\u03b3, FOXO-1, Ki-67, Bax, and Bcl-2 signaling pathways","volume":"393","author":"Mansour","year":"2020","journal-title":"Naunyn-Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e08117","DOI":"10.1016\/j.heliyon.2021.e08117","article-title":"Facile synthesis and in vitro anticancer evaluation of a new series of tetrahydroquinoline","volume":"7","author":"Fathy","year":"2021","journal-title":"Heliyon"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Arab, H.H., Khames, A., Mohammad, M.K., Alsufyani, S.E., Ashour, A.M., El-Sheikh, A.A.K., Darwish, H.W., and Gad, A.M. (2023). Meloxicam Targets COX-2\/NOX1\/NOX4\/Nrf2 Axis to Ameliorate the Depression-like Neuropathology Induced by Chronic Restraint Stress in Rats. Pharmaceuticals, 16.","DOI":"10.3390\/ph16060848"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Arab, H.H., Khames, A., Alsufyani, S.E., El-Sheikh, A.A.K., and Gad, A.M. (2023). Targeting the Endoplasmic Reticulum Stress-Linked PERK\/GRP78\/CHOP Pathway with Magnesium Sulfate Attenuates Chronic-Restraint-Stress-Induced Depression-like Neuropathology in Rats. Pharmaceuticals, 16.","DOI":"10.3390\/ph16020300"},{"key":"ref_32","first-page":"495","article-title":"Synthesis and biological evaluation of new amides pro-drugs containing naproxen moiety as anti-inflammatory and antimicrobial agents","volume":"8","author":"Ammar","year":"2016","journal-title":"Pharma Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"135279","DOI":"10.1016\/j.neulet.2020.135279","article-title":"Beta-amyloid activates NLRP3 inflammasome via TLR4 in mouse microglia","volume":"736","author":"Liu","year":"2020","journal-title":"Neurosci. Lett."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Hassan, M.-A.M., Gad, A.M., Menze, E.T., Badary, O.A., and El-Naga, R.N. (2020). Protective effects of morin against depressive-like behavior prompted by chronic unpredictable mild stress in rats: Possible role of inflammasome-related pathways. Biochem. Pharmacol., 180.","DOI":"10.1016\/j.bcp.2020.114140"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Huang, J., Huang, N., Xu, S., Luo, Y., Li, Y., Jin, H., Yu, C., Shi, J., and Jin, F. (2021). Signaling mechanisms underlying inhibition of neuroinflammation by resveratrol in neurodegenerative diseases. J. Nutr. Biochem., 88.","DOI":"10.1016\/j.jnutbio.2020.108552"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Bai, H., and Zhang, Q. (2021). Activation of NLRP3 Inflammasome and Onset of Alzheimer\u2019s Disease. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.701282"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"939","DOI":"10.3233\/JAD-210268","article-title":"NLRP3 Inflammasome: A Starring Role in Amyloid-\u03b2- and Tau-Driven Pathological Events in Alzheimer\u2019s Disease","volume":"83","author":"Dias","year":"2021","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Hulse, J., and Bhaskar, K. (2022). Crosstalk Between the NLRP3 Inflammasome\/ASC Speck and Amyloid Protein Aggregates Drives Disease Progression in Alzheimer\u2019s and Parkinson\u2019s Disease. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.805169"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Anwar, H.M., Georgy, G.S., Hamad, S.R., Badr, W.K., El Raey, M.A., Abdelfattah, M.A.O., Wink, M., and Sobeh, M. (2021). A Leaf Extract of Harrisonia abyssinica Ameliorates Neurobehavioral, Histological and Biochemical Changes in the Hippocampus of Rats with Aluminum Chloride-Induced Alzheimer\u2019s Disease. Antioxidants, 10.","DOI":"10.3390\/antiox10060947"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1186\/s13041-019-0525-5","article-title":"Restoring Wnt\/\u03b2-catenin signaling is a promising therapeutic strategy for Alzheimer\u2019s disease","volume":"12","author":"Jia","year":"2019","journal-title":"Mol. Brain"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6545","DOI":"10.1523\/JNEUROSCI.0421-09.2009","article-title":"Interruption of \u03b2-Catenin Signaling Reduces Neurogenesis in Alzheimer\u2019s Disease","volume":"29","author":"He","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1080\/17460441.2020.1746266","article-title":"Targeting the Wnt\/\u03b2-catenin pathway in neurodegenerative diseases: Recent approaches and current challenges","volume":"15","author":"Serafino","year":"2020","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1111\/j.1527-3458.2001.tb00204.x","article-title":"Donepezil for Alzheimer\u2019s Disease: Pharmacodynamic, Pharmacokinetic, and Clinical Profiles","volume":"7","author":"Shigeta","year":"2001","journal-title":"CNS Drug Rev."},{"key":"ref_44","first-page":"CD001191","article-title":"Rivastigmine for Alzheimer\u2019s disease","volume":"2015","author":"Birks","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.2165\/00003495-200666110-00015","article-title":"Memantine","volume":"66","author":"Robinson","year":"2006","journal-title":"Drugs"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1517\/17425251003592137","article-title":"Galantamine for Alzheimer\u2019s disease","volume":"6","author":"Prvulovic","year":"2010","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"615","DOI":"10.3233\/JAD-132690","article-title":"Efficacy and Safety of Donepezil, Galantamine, Rivastigmine, and Memantine for the Treatment of Alzheimer\u2019s Disease: A Systematic Review and Meta-Analysis","volume":"41","author":"Tan","year":"2014","journal-title":"J. Alzheimers Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.mehy.2004.02.031","article-title":"Brain cholinesterases: II. The molecular and cellular basis of Alzheimer\u2019s disease","volume":"63","author":"Shen","year":"2004","journal-title":"Med. Hypotheses"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1023\/A:1022869222652","article-title":"Cholinesterases: New Roles in Brain Function and in Alzheimer\u2019s Disease","volume":"28","author":"Giacobini","year":"2003","journal-title":"Neurochem. Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Jasiecki, J., Targo\u0144ska, M., and Was\u0105g, B. (2021). The Role of Butyrylcholinesterase and Iron in the Regulation of Cholinergic Network and Cognitive Dysfunction in Alzheimer\u2019s Disease Pathogenesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22042033"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.ejmech.2017.03.062","article-title":"Recent progress in the identification of selective butyrylcholinesterase inhibitors for Alzheimer\u2019s disease","volume":"132","author":"Li","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Zhou, Y., Lu, X., Yang, H., Chen, Y., Wang, F., Li, J., Tang, Z., Cheng, X., Yang, Y., and Xu, L. (2019). Discovery of Selective Butyrylcholinesterase (BChE) Inhibitors through a Combination of Computational Studies and Biological Evaluations. Molecules, 24.","DOI":"10.3390\/molecules24234217"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"17213","DOI":"10.1073\/pnas.0508575102","article-title":"Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer \u03b2-amyloid peptide in rodent","volume":"102","author":"Greig","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"110451","DOI":"10.1016\/j.cclet.2024.110451","article-title":"Advances in design strategies and imaging applications of specific butyrylcholinesterase probes","volume":"36","author":"Sun","year":"2024","journal-title":"Chin. Chem. Lett."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Stanciu, G.D., Luca, A., Rusu, R.N., Bild, V., Beschea Chiriac, S.I., Solcan, C., Bild, W., and Ababei, D.C. (2020). Alzheimer\u2019s Disease Pharmacotherapy in Relation to Cholinergic System Involvement. Biomolecules, 10.","DOI":"10.3390\/biom10010040"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"10060","DOI":"10.1002\/slct.202002474","article-title":"Synthesis of Various Derivatives of [1,3]Selenazolo[4,5-d]pyrimidine and Exploitation of These Heterocyclic Systems as Antibacterial, Antifungal, and Anticancer Agents","volume":"5","author":"Shiri","year":"2020","journal-title":"ChemistrySelect"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"132839","DOI":"10.1016\/j.molstruc.2022.132839","article-title":"Design, synthesis, in silico studies, in vivo and in vitro assessment of pyridones and thiazolidinones as anti-inflammatory, antipyretic and ulcerogenic hits","volume":"1260","author":"Fayed","year":"2022","journal-title":"J. Mol. Struct."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"24287","DOI":"10.1039\/D4RA03865G","article-title":"The role of current synthetic and possible plant and marine phytochemical compounds in the treatment of acne","volume":"14","author":"Ramsis","year":"2024","journal-title":"RSC Adv."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Rizzo, C., Amata, S., Pibiri, I., Pace, A., Buscemi, S., and Palumbo Piccionello, A. (2023). FDA-Approved Fluorinated Heterocyclic Drugs from 2016 to 2022. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24097728"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"6611","DOI":"10.1039\/C6OB00936K","article-title":"Modern advances in heterocyclic chemistry in drug discovery","volume":"14","author":"Taylor","year":"2016","journal-title":"Org. Biomol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Kassab, A.E., Gedawy, E.M., and Sayed, A.S. (2024). Fused thiophene as a privileged scaffold: A review on anti-Alzheimer\u2019s disease potentials via targeting cholinesterases, monoamine oxidases, glycogen synthase kinase-3, and A\u03b2 aggregation. Int. J. Biol. Macromol., 265.","DOI":"10.1016\/j.ijbiomac.2024.131018"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3196","DOI":"10.2174\/1871520622666220404082648","article-title":"Heterocyclic Compounds: Importance in Anticancer Drug Discovery","volume":"22","author":"Kumar","year":"2022","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"35656","DOI":"10.1021\/acsomega.2c03444","article-title":"Novel Thiophene Thioglycosides Substituted with the Benzothiazole Moiety: Synthesis, Characterization, Antiviral and Anticancer Evaluations, and NS3\/4A and USP7 Enzyme Inhibitions","volume":"7","author":"Azzam","year":"2022","journal-title":"ACS Omega"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"da Cruz, R.M.D., Mendon\u00e7a-Junior, F.J.B., de M\u00e9lo, N.B., Scotti, L., de Ara\u00fajo, R.S.A., de Almeida, R.N., and de Moura, R.O. (2021). Thiophene-Based Compounds with Potential Anti-Inflammatory Activity. Pharmaceuticals, 14.","DOI":"10.3390\/ph14070692"},{"key":"ref_65","first-page":"1241","article-title":"Design, Synthesis, and biological evaluation of a novel series of thiazole derivatives based on pyrazoline as anticancer agents","volume":"65","author":"Fathy","year":"2022","journal-title":"Egypt. J. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s13065-018-0511-5","article-title":"Therapeutic importance of synthetic thiophene","volume":"12","author":"Shah","year":"2018","journal-title":"Chem. Cent. J."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Pathania, S., and Chawla, P.A. (2020). Thiophene-based derivatives as anticancer agents: An overview on decade\u2019s work. Bioorg. Chem., 101.","DOI":"10.1016\/j.bioorg.2020.104026"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2178","DOI":"10.1021\/jm00129a026","article-title":"Benzo- and pyrido-1,4-oxazepin-5-ones and -thiones: Synthesis and structure-activity relationships of a new series of H1-antihistamines","volume":"32","author":"Cale","year":"1989","journal-title":"J. Med. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"793","DOI":"10.2174\/138955707781387876","article-title":"Current Scenario of 1,4-Diazepines as Potent Biomolecules-A Mini Review","volume":"7","author":"Ramajayam","year":"2007","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"117201","DOI":"10.1016\/j.ejmech.2024.117201","article-title":"Discovery of novel bicyclic and tricyclic cyclohepta[b]thiophene derivatives as multipotent AChE and BChE inhibitors, In-Vivo and In-Vitro assays, ADMET and molecular docking simulation","volume":"284","author":"Fayed","year":"2025","journal-title":"Eur. J. Med. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1515\/hc-2016-0236","article-title":"Synthesis of a new polycyclic heterocyclic ring system. Part III. Benzo[b]imidazo[1,5-d][1,4]oxazepine-1,4(2H,5H)-diones","volume":"23","author":"Stanisheva","year":"2017","journal-title":"Heterocycl. Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1002\/jhet.4349","article-title":"Heterocyclic compounds as antiviral drugs: Synthesis, structure\u2013activity relationship and traditional applications","volume":"58","author":"Martins","year":"2021","journal-title":"J. Heterocycl. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"o1541","DOI":"10.1107\/S1600536805012808","article-title":"Ethyl 2-amino-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-3-carboxylate","volume":"61","author":"Nirmala","year":"2005","journal-title":"Acta Crystallogr. Sect. E"},{"key":"ref_74","first-page":"77","article-title":"Synthesis, characterization and pharmacological evaluation of some new 1, 4-diazepine derivatives as anticancer agents","volume":"8","author":"Fayed","year":"2016","journal-title":"Pharma Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3584","DOI":"10.1002\/ejoc.201600496","article-title":"Efficient O-Acylation of Alcohols and Phenol Using Cp2TiCl as a Reaction Promoter","volume":"2016","author":"Hanson","year":"2016","journal-title":"Eur. J. Org. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"69","DOI":"10.3390\/chemistry1010006","article-title":"Acetylation of Alcohols, Amines, Phenols, Thiols under Catalyst and Solvent-Free Conditions","volume":"1","author":"Anbu","year":"2019","journal-title":"Chemistry"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Gavin, J.T., Annor-Gyamfi, J.K., and Bunce, R.A. (2018). Quinazolin-4(3H)-ones and 5,6-Dihydropyrimidin-4(3H)-ones from \u03b2-Aminoamides and Orthoesters. Molecules, 23.","DOI":"10.3390\/molecules23112925"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Annor-Gyamfi, J.K., and Bunce, R.A. (2019). 4H-Benzo[d][1,3]oxazin-4-ones and Dihydro Analogs from Substituted Anthranilic Acids and Orthoesters. Molecules, 24.","DOI":"10.3390\/molecules24193555"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2100454","DOI":"10.1002\/ardp.202100454","article-title":"Upregulation of BAX and caspase-3, as well as downregulation of Bcl-2 during treatment with indeno[1,2-b]quinoxalin derivatives, mediated apoptosis in human cancer cells","volume":"355","author":"Fayed","year":"2022","journal-title":"Arch. Pharm."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"7559","DOI":"10.1021\/jm060642i","article-title":"Structure\u2212Brain Exposure Relationships","volume":"49","author":"Hitchcock","year":"2006","journal-title":"J. Med. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.ejps.2013.04.024","article-title":"1,4-Substituted 4-(1H)-pyridylene-hydrazone-type inhibitors of AChE, BuChE, and amyloid-\u03b2 aggregation crossing the blood\u2013brain barrier","volume":"49","author":"Prinz","year":"2013","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1021\/acs.jcim.6b00465","article-title":"Phantom PAINS: Problems with the Utility of Alerts for Pan-Assay Interference Compounds","volume":"57","author":"Capuzzi","year":"2017","journal-title":"J. Chem Inf. Model."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0169-409X(96)00423-1","article-title":"Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings","volume":"23","author":"Lipinski","year":"1997","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1021\/jm020017n","article-title":"Molecular Properties That Influence the Oral Bioavailability of Drug Candidates","volume":"45","author":"Veber","year":"2002","journal-title":"J. Med. Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1021\/cc9800071","article-title":"A Knowledge-Based Approach in Designing Combinatorial or Medicinal Chemistry Libraries for Drug Discovery. 1. A Qualitative and Quantitative Characterization of Known Drug Databases","volume":"1","author":"Ghose","year":"1999","journal-title":"J. Comb. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1021\/jm015507e","article-title":"Simple Selection Criteria for Drug-like Chemical Matter","volume":"44","author":"Muegge","year":"2001","journal-title":"J. Med. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"3867","DOI":"10.1021\/jm000292e","article-title":"Prediction of Drug Absorption Using Multivariate Statistics","volume":"43","author":"Egan","year":"2000","journal-title":"J. Med. Chem."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures","volume":"58","author":"Pires","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"W257","DOI":"10.1093\/nar\/gky318","article-title":"ProTox-II: A webserver for the prediction of toxicity of chemicals","volume":"46","author":"Banerjee","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Cui, W., Sun, C., Ma, Y., Wang, S., Wang, X., and Zhang, Y. (2020). Inhibition of TLR4 Induces M2 Microglial Polarization and Provides Neuroprotection via the NLRP3 Inflammasome in Alzheimer\u2019s Disease. Front. Neurosci., 14.","DOI":"10.3389\/fnins.2020.00444"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"330","DOI":"10.2174\/157018011794839448","article-title":"Synthesis and Anxiolytic Activity of Some Novel 5-oxo-1, 4-oxazepine Derivatives","volume":"8","author":"AbdelFattah","year":"2011","journal-title":"Lett. Drug Des. Discov."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"110239","DOI":"10.1016\/j.intimp.2023.110239","article-title":"NLRP3 inflammasome inhibition and M1-to-M2 microglial polarization shifting via scoparone-inhibited TLR4 axis in ovariectomy\/D-galactose Alzheimer\u2019s disease rat model","volume":"119","author":"Ibrahim","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/0165-0270(84)90007-4","article-title":"Developments of a water-maze procedure for studying spatial learning in the rat","volume":"11","author":"Morris","year":"1984","journal-title":"J. Neurosci. Methods"},{"key":"ref_94","unstructured":"Guest, P.C. (2019). The Y-Maze for Assessment of Spatial Working and Reference Memory in Mice. Pre-Clinical Models: Techniques and Protocols, Springer."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0026-265X(78)90034-6","article-title":"Further modification of a fluorometric method for analyzing brain amines","volume":"23","author":"Ciarlone","year":"1978","journal-title":"Microchem. J."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1111\/j.1432-1033.1974.tb03714.x","article-title":"Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase","volume":"47","author":"Marklund","year":"1974","journal-title":"Eur. J. Biochem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1136\/jcp.54.5.356","article-title":"Method for the measurement of antioxidant activity in human fluids","volume":"54","author":"Koracevic","year":"2001","journal-title":"J. Clin. Pathol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.imlet.2005.08.001","article-title":"Proinflammatory cytokine (IL-1\u03b2, IL-6, IL-12, IL-18 and TNF-\u03b1) levels in sera of patients with subacute cutaneous lupus erythematosus (SCLE)","volume":"102","author":"Maczynska","year":"2006","journal-title":"Immunol. Lett."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/0006-2952(61)90145-9","article-title":"A new and rapid colorimetric determination of acetylcholinesterase activity","volume":"7","author":"Ellman","year":"1961","journal-title":"Biochem. Pharmacol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Soliman, A.F., Sabry, M.A., and Abdelwahab, G. (2023). Araucaria heterophylla oleogum resin essential oil is a novel aldose reductase and butyryl choline esterase enzymes inhibitor: In vitro and in silico evidence. Sci. Rep., 13.","DOI":"10.1038\/s41598-023-38143-4"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"9695","DOI":"10.1021\/acs.jmedchem.0c00756","article-title":"MicroRNA-Based Multitarget Approach for Alzheimer\u2019s Disease: Discovery of the First-In-Class Dual Inhibitor of Acetylcholinesterase and MicroRNA-15b Biogenesis","volume":"63","author":"Gabr","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"4926151","DOI":"10.1155\/2023\/4926151","article-title":"Effect of Rosa damascena Extract on Rat Model Alzheimer\u2019s Disease: A Histopathological, Behavioral, Enzyme Activities, and Oxidative Stress Study","volume":"2023","author":"Hosseini","year":"2023","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s00702-015-1394-4","article-title":"Staging of cognitive deficits and neuropathological and ultrastructural changes in streptozotocin-induced rat model of Alzheimer\u2019s disease","volume":"122","author":"Knezovic","year":"2015","journal-title":"J. Neural Transm."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"136663","DOI":"10.1016\/j.molstruc.2023.136663","article-title":"Pyrano-coumarin hybrids as potential antimicrobial agents against MRSA strains: Design, synthesis, ADMET, molecular docking studies, as DNA gyrase inhibitors","volume":"1295","author":"Fayed","year":"2024","journal-title":"J. Mol. Struct."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"137374","DOI":"10.1016\/j.molstruc.2023.137374","article-title":"Fluorinated thiazole\u2013thiosemicarbazones hybrids as potential PPAR-\u03b3 agonist and \u03b1-amylase, \u03b1-glucosidase antagonists: Design, synthesis, in silico ADMET and docking studies and hypoglycemic evaluation","volume":"1301","author":"Fayed","year":"2024","journal-title":"J. Mol. Struct."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"2367128","DOI":"10.1080\/14756366.2024.2367128","article-title":"Fluorinated indeno-quinoxaline bearing thiazole moieties as hypoglycaemic agents targeting \u03b1-amylase, and \u03b1-glucosidase: Synthesis, molecular docking, and ADMET studies","volume":"39","author":"Gohar","year":"2024","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"W5","DOI":"10.1093\/nar\/gkab255","article-title":"ADMETlab 2.0: An integrated online platform for accurate and comprehensive predictions of ADMET properties","volume":"49","author":"Xiong","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13321-018-0283-x","article-title":"ADMETlab: A platform for systematic ADMET evaluation based on a comprehensively collected ADMET database","volume":"10","author":"Dong","year":"2018","journal-title":"J. Cheminform."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"10282","DOI":"10.1021\/jm300871x","article-title":"Structures of human acetylcholinesterase in complex with pharmacologically important ligands","volume":"55","author":"Cheung","year":"2012","journal-title":"J. Med. Chem."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1042\/BJ20130013","article-title":"Crystal structures of human cholinesterases in complex with huprine W and tacrine: Elements of specificity for anti-Alzheimer\u2019s drugs targeting acetyl- and butyryl-cholinesterase","volume":"453","author":"Nachon","year":"2013","journal-title":"Biochem. J."},{"key":"ref_111","unstructured":"Molecular Operating Environment (MOE) (2025, February 01). 2014.09 Chemical Computing Group ULC, 1010 Sherbooke St. West, Suite #910, Montreal, QC, Canada, H3A 2R7. Available online: https:\/\/www.chemcomp.com\/."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1186\/s13568-023-01633-9","article-title":"Interception of Epoxide ring to quorum sensing system in Enterococcus faecalis and Staphylococcus aureus","volume":"13","author":"Refai","year":"2023","journal-title":"AMB Express"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s00044-022-03004-8","article-title":"Novel fluorinated pyrazole-based heterocycles scaffold: Cytotoxicity, in silico studies and molecular modelling targeting double mutant EGFR L858R\/T790M as antiproliferative and apoptotic agents","volume":"32","author":"Fayed","year":"2023","journal-title":"Med. Chem. Res."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Abusaif, M.S., Ragab, A., Fayed, E.A., Ammar, Y.A., Gowifel, A.M.H., Hassanin, S.O., Ahmed, G.E., and Gohar, N.A. (2025). Exploring a novel thiazole derivatives hybrid with fluorinated-indenoquinoxaline as dual inhibitors targeting VEGFR2\/AKT and apoptosis inducers against hepatocellular carcinoma with docking simulation. Bioorg. Chem., 154.","DOI":"10.1016\/j.bioorg.2024.108023"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3687","DOI":"10.1016\/j.bmcl.2004.05.017","article-title":"Design, synthesis and cytotoxic studies on the simplified oxy analog of eleutherobin","volume":"14","author":"Chandrasekhar","year":"2004","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Desouky, S.E., Abu-Elghait, M., Fayed, E.A., Selim, S., Yousuf, B., Igarashi, Y., Abdel-Wahab, B.A., Mohammed Alsuhaibani, A., Sonomoto, K., and Nakayama, J. (2022). Secondary Metabolites of Actinomycetales as Potent Quorum Sensing Inhibitors Targeting Gram-Positive Pathogens: In Vitro and In Silico Study. Metabolites, 12.","DOI":"10.3390\/metabo12030246"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Ebrahim, M.A., Ramsis, T.M., Gohar, N.A., metwally, S.A., Rushdi, A., and Fayed, E.A. (2025). Novel Pyrrolidine-bearing quinoxaline inhibitors of DNA Gyrase, RNA polymerase and spike glycoprotein. Bioorg. Chem., 156.","DOI":"10.1016\/j.bioorg.2025.108218"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/8\/1214\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:29:33Z","timestamp":1760034573000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/8\/1214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,17]]},"references-count":117,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["ph18081214"],"URL":"https:\/\/doi.org\/10.3390\/ph18081214","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,17]]}}}