{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:13:42Z","timestamp":1790802822667,"version":"4.1.0"},"reference-count":18,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T00:00:00Z","timestamp":1657584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82003624"],"award-info":[{"award-number":["82003624"]}],"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":["81902039"],"award-info":[{"award-number":["81902039"]}],"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":["20YF1458700"],"award-info":[{"award-number":["20YF1458700"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["82003624"],"award-info":[{"award-number":["82003624"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["81902039"],"award-info":[{"award-number":["81902039"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["20YF1458700"],"award-info":[{"award-number":["20YF1458700"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Nowadays, discovering new skeleton antifungal drugs is the direct way to address clinical fungal infections. Pyrylium salt SM21 was screened from a library containing 50,240 small molecules. Several studies about the antifungal activity and mechanism of SM21 have been reported, but the structure\u2013activity relationship of pyrylium salts was not clear. To explore the chemical space of antifungal pyrylium salt SM21, a series of pyrylium salt derivatives were designed and synthesized. Their antifungal activity and structure-activity relationships (SAR) were investigated. Compared with SM21, most of the synthesized compounds exhibited equivalent or improved antifungal activities against Candida albicans in vitro. The synthesized compounds, such as XY10, XY13, XY14, XY16 and XY17 exhibited comparable antifungal activities against C. albicans with MIC values ranging from 0.47 to 1.0 \u03bcM. Fortunately, a compound numbered XY12 showed stronger antifungal activities and lower cytotoxicity was obtained. The MIC of compound XY12 against C. albicans was 0.24 \u03bcM, and the cytotoxicity decreased 20-fold as compared to SM21. In addition, XY12 was effective against fluconazole-resistant C. albicans and other pathogenic Candida species. More importantly, XY12 could significantly increase the survival rate of mice with a systemic C. albicans infection, which suggested the good antifungal activities of XY12 in vitro and in vivo. Our results indicated that structural modification of pyrylium salts could lead to the discovery of new antifungal drugs.<\/jats:p>","DOI":"10.3390\/molecules27144450","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T20:52:41Z","timestamp":1657659161000},"page":"4450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Design, Synthesis and Antifungal Evaluation of Novel Pyrylium Salt In Vitro and In Vivo"],"prefix":"10.3390","volume":"27","author":[{"given":"Yue","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuhao","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Chao","sequence":"additional","affiliation":[{"name":"Experimental Teaching Center of Basic Medicine College, Navel Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulin","family":"Qin","sequence":"additional","affiliation":[{"name":"Fudan University Minhang Hospital, Shanghai 201199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayan","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingwen","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runhui","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quanzhen","family":"Lv","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9561-7633","authenticated-orcid":false,"given":"Jinxin","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Naval Medical University, Shanghai 200433, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17120","DOI":"10.1038\/nmicrobiol.2017.120","article-title":"Stop neglecting fungi","volume":"2","author":"Jermy","year":"2017","journal-title":"Nat. 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