{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:37:19Z","timestamp":1792442239585,"version":"4.5.0"},"reference-count":67,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["21971222"],"award-info":[{"award-number":["21971222"]}],"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":["22277106"],"award-info":[{"award-number":["22277106"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LR23H300001"],"award-info":[{"award-number":["LR23H300001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018619","name":"National Program for Support of Top-notch Young Professionals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Acute lung injury (ALI) is one of the most common complications in COVID\u201019 and also a syndrome of acute respiratory failure with high mortality rates, but lacks effective therapeutic drugs. Natural products provide inspiration and have proven to be the most valuable source for bioactive molecule discovery. In this study, the chemical evolution of the natural product Tanshinone IIA (Tan\u2010IIA) to achieve a piperidine\u2010fused scaffold through a synthetic route of pre\u2010activation, multi\u2010component reaction, and post\u2010modification is presented. Through biological evaluation, it is pinpointed that compound <jats:bold>8b<\/jats:bold> is a standout candidate with remarkable anti\u2010inflammation and anti\u2010oxidative stress properties, coupled with low toxicity. The mechanistic study unveils a multifaceted biological profile of <jats:bold>8b<\/jats:bold> and shows that <jats:bold>8b<\/jats:bold> is highly efficient in vivo for the treatment of ALI. Therefore, this work not only provides an effective strategy for the treatment of ALI, but also offers a distinctive natural product\u2010inspired drug discovery.<\/jats:p>","DOI":"10.1002\/advs.202305432","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T07:20:41Z","timestamp":1703143241000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Chemical Evolution and Biological Evaluation of Natural Products for Efficient Therapy of Acute Lung Injury"],"prefix":"10.1002","volume":"11","author":[{"given":"Chengcheng","family":"Fan","sequence":"first","affiliation":[{"name":"Institute of Drug Discovery and Design College of Pharmaceutical Sciences National Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang University  866 Yuhangtang Road Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences Zhejiang Chinese Medical University  Hangzhou 311402 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhencheng","family":"Lai","sequence":"additional","affiliation":[{"name":"Institute of Drug Discovery and Design College of Pharmaceutical Sciences National Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang University  866 Yuhangtang Road Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanzi","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences Zhejiang Chinese Medical University  Hangzhou 311402 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaming","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Drug Discovery and Design College of Pharmaceutical Sciences National Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang University  866 Yuhangtang Road Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Drug Discovery and Design College of Pharmaceutical Sciences National Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang University  866 Yuhangtang Road Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Drug Discovery and Design College of Pharmaceutical Sciences National Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang University  866 Yuhangtang Road Hangzhou 310058 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueping","family":"Hu","sequence":"additional","affiliation":[{"name":"Institute of Molecular Sciences and Engineering Institute of Frontier and Interdisciplinary Science Shandong University  Qingdao 266237 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huajun","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Sciences Zhejiang Chinese Medical University  Hangzhou 311402 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9407-5190","authenticated-orcid":false,"given":"Sunliang","family":"Cui","sequence":"additional","affiliation":[{"name":"Institute of Drug Discovery and Design College of Pharmaceutical Sciences National Key Laboratory of Advanced Drug Delivery and Release Systems Zhejiang University  866 Yuhangtang Road Hangzhou 310058 China"},{"name":"Jinhua Institute of Zhejiang University  Jinhua Zhejiang 321299 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.631256"},{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(67)90168-7"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.09.050"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2022.100569"},{"key":"e_1_2_9_2_3","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abd2071"},{"key":"e_1_2_9_2_4","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202301085"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.1c00866"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2007.1940"},{"key":"e_1_2_9_3_3","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2016.29"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.01.028"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201107616"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202008835"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200454004"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200805900"},{"key":"e_1_2_9_6_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200904761"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201402239"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-00114-z"},{"key":"e_1_2_9_7_3","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.0c00922"},{"key":"e_1_2_9_7_4","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.1506"},{"key":"e_1_2_9_7_5","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201907853"},{"key":"e_1_2_9_7_6","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201412074"},{"key":"e_1_2_9_7_7","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.2c07937"},{"key":"e_1_2_9_7_8","volume":"62","author":"Zhou Y. F.","year":"2023","journal-title":"Angew. Chem., Int. Ed."},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/c0np00035c"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543776.2013.736494"},{"key":"e_1_2_9_8_3","doi-asserted-by":"publisher","DOI":"10.2174\/0929867327666200521124850"},{"key":"e_1_2_9_8_4","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2021.105661"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0040165"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2009.08.010"},{"key":"e_1_2_9_9_3","first-page":"195","volume":"40","author":"Yang J.","year":"2016","journal-title":"Cell Physiol."},{"key":"e_1_2_9_9_4","first-page":"2955","volume":"18","author":"Wang Y.","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"e_1_2_9_9_5","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13350"},{"key":"e_1_2_9_9_6","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.34.1052"},{"key":"e_1_2_9_9_7","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2014.112"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28088-z"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01967"},{"key":"e_1_2_9_11_1","unstructured":"CCDC 2177105."},{"key":"e_1_2_9_12_1","unstructured":"CCDC 2153324."},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1250020"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc0269"},{"key":"e_1_2_9_13_3","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2012.09.004"},{"key":"e_1_2_9_13_4","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2011.06.004"},{"key":"e_1_2_9_13_5","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2016.02.002"},{"key":"e_1_2_9_13_6","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c00390"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9SC00086K"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-020-01981-4"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-10386-8"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abp8798"},{"key":"e_1_2_9_15_3","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaz7628"},{"key":"e_1_2_9_15_4","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11624"},{"key":"e_1_2_9_15_5","doi-asserted-by":"publisher","DOI":"10.3390\/biom10020199"},{"key":"e_1_2_9_15_6","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18764-3"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35525-6"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/med.21396"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c02094"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102389"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11624"},{"key":"e_1_2_9_18_3","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b00358"},{"key":"e_1_2_9_18_4","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b01865"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c02094"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2017.10.029"},{"key":"e_1_2_9_19_3","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.3c00197"},{"key":"e_1_2_9_19_4","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01134"},{"key":"e_1_2_9_19_5","doi-asserted-by":"publisher","DOI":"10.1021\/jm100529e"},{"key":"e_1_2_9_19_6","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c00170"},{"key":"e_1_2_9_19_7","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b00934"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-021-00855-6"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202305432","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T13:05:27Z","timestamp":1759755927000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202305432"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,21]]},"references-count":67,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/advs.202305432"],"URL":"https:\/\/doi.org\/10.1002\/advs.202305432","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,21]]},"assertion":[{"value":"2023-08-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2305432"}}