{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:05:42Z","timestamp":1785330342992,"version":"3.55.0"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":26,"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"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274221"],"award-info":[{"award-number":["82274221"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82274236"],"award-info":[{"award-number":["82274236"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"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                    In this work, \u03b1\u2010glucosidase was chosen as the main therapeutic target. Novel flavone\u2010cinnamic acid hybrid derivatives were designed, synthesized, and structurally identified based on flavone prototypes with intrinsic \u03b1\u2010glucosidase inhibitory effects. Considering the multi\u2010target pathological features of diabetes, \u03b1\u2010glucosidase inhibition, lipase inhibition, DPPH radical scavenging capacities, and insulin\u2010resistant HepG2 cell assays were systematically evaluated to clarify their hypoglycemic mechanisms. Most acacetin\u2010cinnamic acid hybrid derivatives exerted strong dual inhibitory effects on the two enzymes, with\n                    <jats:bold>6c<\/jats:bold>\n                    and\n                    <jats:bold>6l<\/jats:bold>\n                    showing the best \u03b1\u2010glucosidase and lipase inhibitory activity, respectively, at the concentration of 50 \u00b5M. In the baicalein\u2010cinnamic acid hybrid derivatives, only\n                    <jats:bold>7a<\/jats:bold>\n                    possessed prominent lipase inhibition, while other analogues were weak in enzyme inhibition but superior to parent baicalein. Notably, baicalein\u2010cinnamic acid hybrid derivatives presented outstanding antioxidant activity, and significantly enhanced glucose uptake in insulin\u2010resistant HepG2 cells, among which\n                    <jats:bold>7f<\/jats:bold>\n                    and\n                    <jats:bold>7i<\/jats:bold>\n                    were the most promising candidates. Enzyme inhibition and antioxidant properties jointly determined their cellular hypoglycemic effects. Overall, these hybrids exert anti\u2010diabetic effects via synergistic multi\u2010pathway actions, and\n                    <jats:bold>7f<\/jats:bold>\n                    and\n                    <jats:bold>7i<\/jats:bold>\n                    deserve further in\u2010depth mechanistic research.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.71501","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T18:56:55Z","timestamp":1785178615000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Series of Flavone\u2010Cinnamic Acid Hybrid Derivatives as Hypoglycemic Agents: Design, Synthesis, and Activity Studies"],"prefix":"10.1002","volume":"23","author":[{"given":"Xiangxiang","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry School of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajia","family":"Mou","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry School of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guizhi","family":"Xiao","sequence":"additional","affiliation":[{"name":"Tianjin Institute of Pharmaceutical Research Co. Ltd.  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry School of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry School of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanru","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry School of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20102125.1999.00092.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.obpill.2023.100076"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2021.03.003"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2025.112152"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2022.108332"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2018.11.008"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2018.10.004"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2024.07.017"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107367"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2018.01.015"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2025.106647"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3945\/an.116.012948"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2014.07.013"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5RA01818H"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2015.10.017"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2022.105301"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2022.106028"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phyplu.2024.100632"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2020.111708"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.foodchem.2022.133561"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fbio.2024.105076"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytochem.2022.113532"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960\u2010894X(99)00092\u2010X"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.28.2231"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/cbdd.13917"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.105466"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jasms.2007.01.006"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.11.094"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2025.141883"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.01.012"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sjbs.2015.09.005"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107783"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lwt.2024.117208"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.134058"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2023.125679"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxcx.2024.100209"}],"container-title":["Chemistry &amp; Biodiversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.71501","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbdv.71501","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.71501","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:27:27Z","timestamp":1785328047000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbdv.71501"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":36,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/cbdv.71501"],"URL":"https:\/\/doi.org\/10.1002\/cbdv.71501","archive":["Portico"],"relation":{},"ISSN":["1612-1872","1612-1880"],"issn-type":[{"value":"1612-1872","type":"print"},{"value":"1612-1880","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-01-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e71501"}}