{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T16:53:48Z","timestamp":1786985628586,"version":"build-2736575974"},"reference-count":18,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2021,10,10]],"date-time":"2021-10-10T00:00:00Z","timestamp":1633824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LGF20C090003"],"award-info":[{"award-number":["LGF20C090003"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The main mechanism of pyroptosis is Caspase\u20101\u2013mediated GSDMD cleavage, and GSDMD is also the executive protein of pyroptosis. Our previous study has shown that mafenide can inhibit pyroptosis by inhibiting the GSDMD\u2010Asp275\u00a0site to suppress cleavage. In this study, sulfonamide was used as the parent nucleus structure to synthesize sulfa\u20104 and sulfa\u201020. Screening of drug activity in the pyroptosis model of BV2 and iBMDM cell lines revealed the efficacy of five compounds were superior to mafenide, which exerted a better inhibitory effect on the occurrence of pyroptosis. For in vivo assay, Sulfa\u20104 and Sulfa\u201022 were intervened in the neuroinflammation APP\/PS1\u00a0mice. As a result, the administration of Sulfa\u20104 and Sulfa\u201022 could significantly inhibit the activation of microglia, decrease the expression of inflammatory factors in the central nervous system and simultaneously suppress the production of p30\u2010GSDMD as well as the expression of upstream NLRP3 inflammasome and Caspase\u20101 protein. Immunoprecipitation and Biotin\u2010labelled assay confirmed the targeted binding relationship of Sulfa\u20104 and Sulfa\u201022 with GSDMD protein in the iBMDM model in vitro. In this study, we investigated a new type inhibitor of GSDMD cleavage, which exerted a good inhibitory effect on pyroptosis and provided new references for the development of inflammatory drugs in the future.<\/jats:p>","DOI":"10.1111\/jcmm.16984","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T04:05:39Z","timestamp":1633925139000},"page":"10534-10542","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Mafenide derivatives inhibit neuroinflammation in Alzheimer's disease by regulating pyroptosis"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2805-580X","authenticated-orcid":false,"given":"Chenyang","family":"Han","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology School of Life Science Nanjing University Nanjing China"},{"name":"Department of Pharmacy The Second Affiliated Hospital of Jiaxing University China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaohong","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology School of Life Science Nanjing University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqi","family":"Yu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology School of Life Science Nanjing University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingcai","family":"Jiao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology School of Life Science Nanjing University Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2519-5217","authenticated-orcid":false,"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The Second Affiliated Hospital of Jiaxing University China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2017.10.025"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jmcb\/mjz020"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2070"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1607769113"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201694696"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.8b00376"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jpi.12414"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.12.018"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.348"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160197"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2020.105303"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12491"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-22871-z"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1017\/cjn.2019.256"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01905"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11655-018-3001-7"},{"issue":"4","key":"e_1_2_10_18_1","first-page":"1971","article-title":"Downregulation of GSDMD attenuates tumor proliferation via the intrinsic mitochondrial apoptotic pathway and inhibition of EGFR\/Akt signaling and predicts a good prognosis in non? 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