{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T09:08:07Z","timestamp":1791623287896,"version":"4.3.4"},"reference-count":48,"publisher":"Wiley","license":[{"start":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T00:00:00Z","timestamp":1721174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82003584"],"award-info":[{"award-number":["82003584"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017055","name":"National Natural Science Foundation of China-Shandong Joint Fund","doi-asserted-by":"publisher","award":["U1906212"],"award-info":[{"award-number":["U1906212"]}],"id":[{"id":"10.13039\/100017055","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019618","name":"Fujian Provincial Key Laboratory for the Development of Bioactive Material from Marine Algae, Quanzhou Normal University","doi-asserted-by":"publisher","award":["2022QNLM030003"],"award-info":[{"award-number":["2022QNLM030003"]}],"id":[{"id":"10.13039\/501100019618","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013280","name":"Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","award":["ZR2019ZD18,ZR2021ZD28"],"award-info":[{"award-number":["ZR2019ZD18,ZR2021ZD28"]}],"id":[{"id":"10.13039\/501100013280","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013280","name":"Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions","doi-asserted-by":"publisher","award":["81991522"],"award-info":[{"award-number":["81991522"]}],"id":[{"id":"10.13039\/501100013280","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019595","name":"Youth and Middle-aged Scientific and Technological Innovation Leading Talents Program of the Corps","doi-asserted-by":"publisher","award":["2021CXLH0012"],"award-info":[{"award-number":["2021CXLH0012"]}],"id":[{"id":"10.13039\/501100019595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Numerous clinical disorders have been linked to the etiology of dysregulated NLRP3 (NACHT, LRR, and PYD domain\u2010containing protein 3) inflammasome activation. Despite its potential as a pharmacological target, modulation of NLRP3 activity remains challenging. Only a sparse number of compounds have been reported that can modulate NLRP3 and none of them have been developed into a commercially available drug. In this research, we identified three potent NLRP3 inflammasome inhibitors, gymnoasins A\u2010C (<jats:bold>1<\/jats:bold>\u2013<jats:bold>3<\/jats:bold>), with unprecedented pentacyclic scaffolds, from an Antarctic fungus <jats:italic>Pseudogymnoascus<\/jats:italic> sp. HDN17\u2010895, which represent the first naturally occurring naphthopyrone\u2010macrolide hybrids. Additionally, biomimetic synthesis of gymnoasin A (<jats:bold>1<\/jats:bold>) was also achieved validating the chemical structure and affording ample amounts of material for exhaustive bioactivity assessments. Biological assays indicated that <jats:bold>1<\/jats:bold> could significantly inhibited in vitro NLRP3 inflammasome activation and in vivo pro\u2010inflammatory cytokine IL\u20101\u03b2 release, representing a valuable new lead compound for the development of novel therapeutics with the potential to inhibit the NLRP3 inflammasome.<\/jats:p>","DOI":"10.1002\/anie.202405860","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T06:43:57Z","timestamp":1717569837000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Discovery, Total Synthesis, and Anti\u2010Inflammatory Evaluation of Naturally Occurring Naphthopyrone\u2010Macrolide Hybrids as Potent NLRP3 Inflammasome Inhibitors"],"prefix":"10.1002","author":[{"given":"Chunxiao","family":"Sun","sequence":"first","affiliation":[{"name":"Key Laboratory of Marine Drugs Ministry of Education School of Medicine and Pharmacy Ocean University of China  Qingdao 266100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Jiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs Ministry of Education School of Medicine and Pharmacy Ocean University of China  Qingdao 266100 China"},{"name":"Laboratory for Marine Drugs and Bioproducts Qingdao National Laboratory for Marine Science and Technology  Qingdao 266237 China"},{"name":"Marine Biomedical Research Institute of Qingdao  Qingdao Shandong 266071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changlong","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs Ministry of Education School of Medicine and Pharmacy Ocean University of China  Qingdao 266100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simin","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs Ministry of Education School of Medicine and Pharmacy Ocean University of China  Qingdao 266100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs Ministry of Education School of Medicine and Pharmacy Ocean University of China  Qingdao 266100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxue","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs Ministry of Education School of Medicine and Pharmacy Ocean University of China  Qingdao 266100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luning","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs Ministry of Education School of Medicine and Pharmacy Ocean University of China  Qingdao 266100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs Ministry of Education School of Medicine and Pharmacy Ocean University of China  Qingdao 266100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mudassir","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Abbottabad University of Science and Technology  Havellian, District Abbottabad 22010 KPK Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Che","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs Ministry of Education School of Medicine and Pharmacy Ocean University of China  Qingdao 266100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guojian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs Ministry of Education School of Medicine and Pharmacy Ocean University of China  Qingdao 266100 China"},{"name":"Laboratory for Marine Drugs and Bioproducts Qingdao National Laboratory for Marine Science and Technology  Qingdao 266237 China"},{"name":"Marine Biomedical Research Institute of Qingdao  Qingdao Shandong 266071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs Ministry of Education School of Medicine and Pharmacy Ocean University of China  Qingdao 266100 China"},{"name":"Laboratory for Marine Drugs and Bioproducts Qingdao National Laboratory for Marine Science and Technology  Qingdao 266237 China"},{"name":"Marine Biomedical Research Institute of Qingdao  Qingdao Shandong 266071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianjiao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs Ministry of Education School of Medicine and Pharmacy Ocean University of China  Qingdao 266100 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7191-2002","authenticated-orcid":false,"given":"Dehai","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Drugs Ministry of Education School of Medicine and Pharmacy Ocean University of China  Qingdao 266100 China"},{"name":"Laboratory for Marine Drugs and Bioproducts Qingdao National Laboratory for Marine Science and Technology  Qingdao 266237 China"},{"name":"Marine Biomedical Research Institute of Qingdao  Qingdao Shandong 266071 China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,17]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20133328"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3893"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2016.09.002"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0165-0"},{"key":"e_1_2_7_5_1","first-page":"15","volume":"8","author":"Ozaki E.","year":"2015","journal-title":"J. Inflamm. Res."},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00670-3"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-018-0900-3"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.315937"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3806"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01250"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1716095115"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04947-6"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20171419"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b01155"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02538"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-1236-z"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b00733"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00211"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25235533"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25235533"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1471-y"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.97"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c01307"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2NP00025C"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxins13050347"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.2c01394"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.1c01118"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.1c00203"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.0c02575"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1039\/b104337b"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.50.878"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.49.95"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.44.762"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo048643a"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr2003344"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/b707989n"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo981810k"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.5b02396"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1071\/CH9871737"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.5b03202"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2012.12.070"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/ol502551u"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja971657w"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.01.054"},{"key":"e_1_2_7_45_1","volume":"131","author":"Guo H.","year":"2020","journal-title":"Curr. Protoc. Bioinforma."},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-023-00822-2"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04467-w"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2016070729"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202405860","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T13:22:36Z","timestamp":1721222556000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202405860"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,17]]},"references-count":48,"alternative-id":["10.1002\/anie.202405860"],"URL":"https:\/\/doi.org\/10.1002\/anie.202405860","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,17]]},"assertion":[{"value":"2024-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-07-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202405860"}}