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Design, Synthesis, and In Vitro and In Vivo Antifungal Activity of Novel Triazoles Containing Phenylethynyl Pyrazole Side Chains

A series of triazole derivatives containing phenylethynyl pyrazole moiety as side chain were designed, synthesized, and most of them exhibited good in vitro antifungal activities. Especially, compounds 5k and 6c showed excellent in vitro activities against C. albicans (MIC = 0.125, 0.0625 μg/mL), C....

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Autores principales: Ni, Tingjunhong, Ding, Zichao, Xie, Fei, Hao, Yumeng, Bao, Junhe, Zhang, Jingxiang, Yu, Shichong, Jiang, Yuanying, Zhang, Dazhi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9182106/
https://www.ncbi.nlm.nih.gov/pubmed/35684308
http://dx.doi.org/10.3390/molecules27113370
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author Ni, Tingjunhong
Ding, Zichao
Xie, Fei
Hao, Yumeng
Bao, Junhe
Zhang, Jingxiang
Yu, Shichong
Jiang, Yuanying
Zhang, Dazhi
author_facet Ni, Tingjunhong
Ding, Zichao
Xie, Fei
Hao, Yumeng
Bao, Junhe
Zhang, Jingxiang
Yu, Shichong
Jiang, Yuanying
Zhang, Dazhi
author_sort Ni, Tingjunhong
collection PubMed
description A series of triazole derivatives containing phenylethynyl pyrazole moiety as side chain were designed, synthesized, and most of them exhibited good in vitro antifungal activities. Especially, compounds 5k and 6c showed excellent in vitro activities against C. albicans (MIC = 0.125, 0.0625 μg/mL), C. neoformans (MIC = 0.125, 0.0625 μg/mL), and A. fumigatus (MIC = 8.0, 4.0 μg/mL). Compound 6c also exerted superior activity to compound 5k and fluconazole in inhibiting hyphae growth of C. albicans and inhibiting drug-resistant strains of C. albicans, and it could reduce fungal burdens in mice kidney at a dosage of 1.0 mg/kg. An in vivo efficacy evaluation indicated that 6c could effectively protect mice models from C. albicans infection at doses of 0.5, 1.0, and 2.0 mg/kg. These results suggested that compound 6c deserves further investigation.
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spelling pubmed-91821062022-06-10 Design, Synthesis, and In Vitro and In Vivo Antifungal Activity of Novel Triazoles Containing Phenylethynyl Pyrazole Side Chains Ni, Tingjunhong Ding, Zichao Xie, Fei Hao, Yumeng Bao, Junhe Zhang, Jingxiang Yu, Shichong Jiang, Yuanying Zhang, Dazhi Molecules Article A series of triazole derivatives containing phenylethynyl pyrazole moiety as side chain were designed, synthesized, and most of them exhibited good in vitro antifungal activities. Especially, compounds 5k and 6c showed excellent in vitro activities against C. albicans (MIC = 0.125, 0.0625 μg/mL), C. neoformans (MIC = 0.125, 0.0625 μg/mL), and A. fumigatus (MIC = 8.0, 4.0 μg/mL). Compound 6c also exerted superior activity to compound 5k and fluconazole in inhibiting hyphae growth of C. albicans and inhibiting drug-resistant strains of C. albicans, and it could reduce fungal burdens in mice kidney at a dosage of 1.0 mg/kg. An in vivo efficacy evaluation indicated that 6c could effectively protect mice models from C. albicans infection at doses of 0.5, 1.0, and 2.0 mg/kg. These results suggested that compound 6c deserves further investigation. MDPI 2022-05-24 /pmc/articles/PMC9182106/ /pubmed/35684308 http://dx.doi.org/10.3390/molecules27113370 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
Ni, Tingjunhong
Ding, Zichao
Xie, Fei
Hao, Yumeng
Bao, Junhe
Zhang, Jingxiang
Yu, Shichong
Jiang, Yuanying
Zhang, Dazhi
Design, Synthesis, and In Vitro and In Vivo Antifungal Activity of Novel Triazoles Containing Phenylethynyl Pyrazole Side Chains
title Design, Synthesis, and In Vitro and In Vivo Antifungal Activity of Novel Triazoles Containing Phenylethynyl Pyrazole Side Chains
title_full Design, Synthesis, and In Vitro and In Vivo Antifungal Activity of Novel Triazoles Containing Phenylethynyl Pyrazole Side Chains
title_fullStr Design, Synthesis, and In Vitro and In Vivo Antifungal Activity of Novel Triazoles Containing Phenylethynyl Pyrazole Side Chains
title_full_unstemmed Design, Synthesis, and In Vitro and In Vivo Antifungal Activity of Novel Triazoles Containing Phenylethynyl Pyrazole Side Chains
title_short Design, Synthesis, and In Vitro and In Vivo Antifungal Activity of Novel Triazoles Containing Phenylethynyl Pyrazole Side Chains
title_sort design, synthesis, and in vitro and in vivo antifungal activity of novel triazoles containing phenylethynyl pyrazole side chains
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9182106/
https://www.ncbi.nlm.nih.gov/pubmed/35684308
http://dx.doi.org/10.3390/molecules27113370
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