{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T21:08:18Z","timestamp":1791925698049,"version":"4.3.4"},"reference-count":88,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,6,3]],"date-time":"2024-06-03T00:00:00Z","timestamp":1717372800000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    A new series of quinoxaline\u2010sulfonamide derivatives\n                    <jats:bold>3<\/jats:bold>\n                    \u2013\n                    <jats:bold>12<\/jats:bold>\n                    were synthesized using fragment\u2010based drug design by reaction of quinoxaline sulfonyl chloride (QSC) with different amines and hydrazines. The quinoxaline\u2010sulfonamide derivatives were evaluated for antidiabetic and anti\u2010Alzheimer's potential against \u03b1\u2010glucosidase, \u03b1\u2010amylase, and acetylcholinesterase enzymes. These derivatives showed good to moderate potency against \u03b1\u2010amylase and \u03b1\u2010glucosidase with inhibitory percentages between 24.34\u2009\u00b1\u20090.01%\u201363.09\u2009\u00b1\u20090.02% and 28.95\u2009\u00b1\u20090.04%\u201375.36\u2009\u00b1\u20090.01%, respectively. Surprisingly,\n                    <jats:italic>bis<\/jats:italic>\n                    \u2010sulfonamide quinoxaline derivative\n                    <jats:bold>4<\/jats:bold>\n                    revealed the most potent activity with inhibitory percentages of 75.36\u2009\u00b1\u20090.01% and 63.09\u2009\u00b1\u20090.02% against\n                    <jats:italic>\u03b1<\/jats:italic>\n                    \u2010glucosidase and \u03b1\u2010amylase compared to acarbose (IP\u2009=\u200957.79\u2009\u00b1\u20090.01% and 67.33\u2009\u00b1\u20090.01%), respectively. Moreover, the quinoxaline derivative\n                    <jats:bold>3<\/jats:bold>\n                    exhibited potency as \u03b1\u2010glucosidase and \u03b1\u2010amylase inhibitory with a minute decline from compound\n                    <jats:bold>4<\/jats:bold>\n                    and acarbose with inhibitory percentages of 44.93\u2009\u00b1\u20090.01% and 38.95\u2009\u00b1\u20090.01%. Additionally, in vitro acetylcholinesterase inhibitory activity for designed derivatives exhibited weak to moderate activity. Still, sulfonamide\u2010quinoxaline derivative\n                    <jats:bold>3<\/jats:bold>\n                    emerged as the most active member with inhibitory percentage of 41.92\u2009\u00b1\u20090.02% compared with donepezil (IP\u2009=\u200967.27\u2009\u00b1\u20090.60%). The DFT calculations, docking simulation, target prediction, and ADMET analysis were performed and discussed in detail.\n                  <\/jats:p>","DOI":"10.1002\/ddr.22216","type":"journal-article","created":{"date-parts":[[2024,6,4]],"date-time":"2024-06-04T00:57:05Z","timestamp":1717462625000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Explore new quinoxaline pharmacophore tethered sulfonamide fragments as in vitro \u03b1\u2010glucosidase, \u03b1\u2010amylase, and acetylcholinesterase inhibitors with ADMET and molecular modeling simulation"],"prefix":"10.1002","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8542-7465","authenticated-orcid":false,"given":"Ahmed","family":"Ragab","sequence":"first","affiliation":[{"name":"Department of Chemistry, Faculty of Science (boys) Al\u2010Azhar University Nasr Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4097-0899","authenticated-orcid":false,"given":"Mohamed A.","family":"Salem","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science and Arts King Khalid University, Mohail, Assir  Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8989-4394","authenticated-orcid":false,"given":"Yousry A.","family":"Ammar","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science (boys) Al\u2010Azhar University Nasr Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4848-0731","authenticated-orcid":false,"given":"Wael M.","family":"Aboulthana","sequence":"additional","affiliation":[{"name":"Biochemistry Department Biotechnology Research Institute, National Research Centre, Dokki Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed H.","family":"Helal","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Arts and Science Northern Border University Rafha Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1084-3904","authenticated-orcid":false,"given":"Moustafa S.","family":"Abusaif","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science (boys) Al\u2010Azhar University Nasr Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsps.2024.102025"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-50130-3"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.134443"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13738-020-02082-y"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtice.2023.105207"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2RA04498F"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-803959-5.50008-8"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2014.12.002"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28207125"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4RA00423J"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.103841"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104164"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.14154"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants11091131"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2019.03.058"},{"key":"e_1_2_8_17_1","article-title":"Design, synthesis of new novel Quinoxalin\u20102(1H)\u2010One derivatives incorporating hydrazone, hydrazine, and pyrazole moieties as antimicrobial potential with in\u2010silico ADME and molecular docking simulation","volume":"2","author":"Askar A.","year":"2021","journal-title":"Arabian Journal of Chemistry"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rechem.2022.100672"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115138"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202200395"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/aoc.7238"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27217248"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11101-021-09773-1"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104497"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10030722"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1515\/hc-2022-0170"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph15030376"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(61)90145-9"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2021.132004"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.133028"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.105300"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1CB00229E"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104270"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants11020232"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26123625"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2022.09.102"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2022.05.040"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.09.016"},{"issue":"6","key":"e_1_2_8_39_1","first-page":"441","article-title":"Synthesis, in vitro biological investigation, and in silico analysis of pyrazole\u2010based derivatives as multi\u2010target agents","volume":"66","author":"Hassan A.","year":"2023","journal-title":"Egyptian Journal of Chemistry"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3RA00297G"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.22008"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/aoc.6508"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3RA01635H"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1840441"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2023.137118"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2019.0071"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00530"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1080\/13813455.2023.2262167"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-6380(00)80016-1"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.1c02373"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145705005833"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschembio.2c00791"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arabjc.2022.103851"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2021.130484"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2023.135671"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1872-2067(15)60845-2"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2018.08.010"},{"key":"e_1_2_8_58_1","unstructured":"Organization W. H.(1980). WHO Expert Committee on diabetes mellitus:Second report. Geneva Switzerland. World Health Organization 1980. WHO Technical Report Series 646."},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202103848"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa031314"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)00877-8"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.21960"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2022.106307"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2022.105473"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arabjc.2021.103497"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics12010128"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3RA07040A"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115180"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3RA04873J"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3RA00887H"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2021.111320"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13738-022-02575-y"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27030830"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1NJ05644A"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01124-1"},{"key":"e_1_2_8_76_1","first-page":"210","volume-title":"Actes du 1 er Colloque Europeen d'Ethnopharmacologie, Office de la Recherche Scientifique et Techniques d'Outre Mer (ORSTOM)","author":"Serrano J. J.","year":"1990"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9NJ02580D"},{"issue":"4","key":"e_1_2_8_78_1","first-page":"166","article-title":"\u03b1 \u2010Amylase production and applications: A review","volume":"2","author":"Sundarram A.","year":"2014","journal-title":"Journal of Applied & Environmental Microbiology"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26164895"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1RA06799K"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c02279"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.microc.2023.108988"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiph.2022.03.002"},{"issue":"1","key":"e_1_2_8_84_1","first-page":"81","article-title":"Tyrosinase, acetyl\u2010and butyryl\u2010cholinesterase inhibitory activity of stachys lavandulifolia vahl (Lamiaceae) and its major constituents","volume":"9","author":"Tundis R.","year":"2015","journal-title":"Records of Natural Products"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-016-1452-y"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2020.115324"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.200900266"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc-2024-0010"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b00017"}],"container-title":["Drug Development Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.22216","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T17:48:26Z","timestamp":1760377706000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/ddr.22216"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6]]},"references-count":88,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/ddr.22216"],"URL":"https:\/\/doi.org\/10.1002\/ddr.22216","archive":["Portico"],"relation":{},"ISSN":["0272-4391","1098-2299"],"issn-type":[{"value":"0272-4391","type":"print"},{"value":"1098-2299","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6]]},"assertion":[{"value":"2024-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-03","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e22216"}}