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Design, Synthesis and Antifungal Evaluation of Novel Pyrylium Salt In Vitro and In Vivo

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–act...

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Autores principales: Zhang, Yue, Li, Qiuhao, Chao, Wen, Qin, Yulin, Chen, Jiayan, Wang, Yingwen, Liu, Runhui, Lv, Quanzhen, Wang, Jinxin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315806/
https://www.ncbi.nlm.nih.gov/pubmed/35889323
http://dx.doi.org/10.3390/molecules27144450
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author Zhang, Yue
Li, Qiuhao
Chao, Wen
Qin, Yulin
Chen, Jiayan
Wang, Yingwen
Liu, Runhui
Lv, Quanzhen
Wang, Jinxin
author_facet Zhang, Yue
Li, Qiuhao
Chao, Wen
Qin, Yulin
Chen, Jiayan
Wang, Yingwen
Liu, Runhui
Lv, Quanzhen
Wang, Jinxin
author_sort Zhang, Yue
collection PubMed
description 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–activity 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 μM. 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 μM, 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.
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spelling pubmed-93158062022-07-27 Design, Synthesis and Antifungal Evaluation of Novel Pyrylium Salt In Vitro and In Vivo Zhang, Yue Li, Qiuhao Chao, Wen Qin, Yulin Chen, Jiayan Wang, Yingwen Liu, Runhui Lv, Quanzhen Wang, Jinxin Molecules Article 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–activity 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 μM. 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 μM, 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. MDPI 2022-07-12 /pmc/articles/PMC9315806/ /pubmed/35889323 http://dx.doi.org/10.3390/molecules27144450 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Yue
Li, Qiuhao
Chao, Wen
Qin, Yulin
Chen, Jiayan
Wang, Yingwen
Liu, Runhui
Lv, Quanzhen
Wang, Jinxin
Design, Synthesis and Antifungal Evaluation of Novel Pyrylium Salt In Vitro and In Vivo
title Design, Synthesis and Antifungal Evaluation of Novel Pyrylium Salt In Vitro and In Vivo
title_full Design, Synthesis and Antifungal Evaluation of Novel Pyrylium Salt In Vitro and In Vivo
title_fullStr Design, Synthesis and Antifungal Evaluation of Novel Pyrylium Salt In Vitro and In Vivo
title_full_unstemmed Design, Synthesis and Antifungal Evaluation of Novel Pyrylium Salt In Vitro and In Vivo
title_short Design, Synthesis and Antifungal Evaluation of Novel Pyrylium Salt In Vitro and In Vivo
title_sort design, synthesis and antifungal evaluation of novel pyrylium salt in vitro and in vivo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315806/
https://www.ncbi.nlm.nih.gov/pubmed/35889323
http://dx.doi.org/10.3390/molecules27144450
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