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The newly synthesized thiazole derivatives as potential antifungal compounds against Candida albicans

ABSTRACT: Recently, the occurrence of candidiasis has increased dramatically, especially in immunocompromised patients. Additionally, their treatment is often ineffective due to the resistance of yeasts to antimycotics. Therefore, there is a need to search for new antifungals. A series of nine newly...

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Autores principales: Biernasiuk, Anna, Berecka-Rycerz, Anna, Gumieniczek, Anna, Malm, Maria, Łączkowski, Krzysztof Z., Szymańska, Jolanta, Malm, Anna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374424/
https://www.ncbi.nlm.nih.gov/pubmed/34410437
http://dx.doi.org/10.1007/s00253-021-11477-7
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author Biernasiuk, Anna
Berecka-Rycerz, Anna
Gumieniczek, Anna
Malm, Maria
Łączkowski, Krzysztof Z.
Szymańska, Jolanta
Malm, Anna
author_facet Biernasiuk, Anna
Berecka-Rycerz, Anna
Gumieniczek, Anna
Malm, Maria
Łączkowski, Krzysztof Z.
Szymańska, Jolanta
Malm, Anna
author_sort Biernasiuk, Anna
collection PubMed
description ABSTRACT: Recently, the occurrence of candidiasis has increased dramatically, especially in immunocompromised patients. Additionally, their treatment is often ineffective due to the resistance of yeasts to antimycotics. Therefore, there is a need to search for new antifungals. A series of nine newly synthesized thiazole derivatives containing the cyclopropane system, showing promising activity against Candida spp., has been further investigated. We decided to verify their antifungal activity towards clinical Candida albicans isolated from the oral cavity of patients with hematological malignancies and investigate the mode of action on fungal cell, the effect of combination with the selected antimycotics, toxicity to erythrocytes, and lipophilicity. These studies were performed by the broth microdilution method, test with sorbitol and ergosterol, checkerboard technique, erythrocyte lysis assay, and reversed phase thin-layer chromatography, respectively. All derivatives showed very strong activity (similar and even higher than nystatin) against all C. albicans isolates with minimal inhibitory concentration (MIC) = 0.008–7.81 µg/mL Their mechanism of action may be related to action within the fungal cell wall structure and/or within the cell membrane. The interactions between the derivatives and the selected antimycotics (nystatin, chlorhexidine, and thymol) showed additive effect only in the case of combination some of them and thymol. The erythrocyte lysis assay confirmed the low cytotoxicity of these compounds as compared to nystatin. The high lipophilicity of the derivatives was related with their high antifungal activity. The present studies confirm that the studied thiazole derivatives containing the cyclopropane system appear to be a very promising group of compounds in treatment of infections caused by C. albicans. However, this requires further studies in vivo. KEY POINTS: • The newly thiazoles showed high antifungal activity and some of them — additive effect in combination with thymol. • Their mode of action may be related with the influence on the structure of the fungal cell wall and/or the cell membrane. • The low cytotoxicity against erythrocytes and high lipophilicity of these derivatives are their additional good properties. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00253-021-11477-7.
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spelling pubmed-83744242021-08-19 The newly synthesized thiazole derivatives as potential antifungal compounds against Candida albicans Biernasiuk, Anna Berecka-Rycerz, Anna Gumieniczek, Anna Malm, Maria Łączkowski, Krzysztof Z. Szymańska, Jolanta Malm, Anna Appl Microbiol Biotechnol Biotechnological Products and Process Engineering ABSTRACT: Recently, the occurrence of candidiasis has increased dramatically, especially in immunocompromised patients. Additionally, their treatment is often ineffective due to the resistance of yeasts to antimycotics. Therefore, there is a need to search for new antifungals. A series of nine newly synthesized thiazole derivatives containing the cyclopropane system, showing promising activity against Candida spp., has been further investigated. We decided to verify their antifungal activity towards clinical Candida albicans isolated from the oral cavity of patients with hematological malignancies and investigate the mode of action on fungal cell, the effect of combination with the selected antimycotics, toxicity to erythrocytes, and lipophilicity. These studies were performed by the broth microdilution method, test with sorbitol and ergosterol, checkerboard technique, erythrocyte lysis assay, and reversed phase thin-layer chromatography, respectively. All derivatives showed very strong activity (similar and even higher than nystatin) against all C. albicans isolates with minimal inhibitory concentration (MIC) = 0.008–7.81 µg/mL Their mechanism of action may be related to action within the fungal cell wall structure and/or within the cell membrane. The interactions between the derivatives and the selected antimycotics (nystatin, chlorhexidine, and thymol) showed additive effect only in the case of combination some of them and thymol. The erythrocyte lysis assay confirmed the low cytotoxicity of these compounds as compared to nystatin. The high lipophilicity of the derivatives was related with their high antifungal activity. The present studies confirm that the studied thiazole derivatives containing the cyclopropane system appear to be a very promising group of compounds in treatment of infections caused by C. albicans. However, this requires further studies in vivo. KEY POINTS: • The newly thiazoles showed high antifungal activity and some of them — additive effect in combination with thymol. • Their mode of action may be related with the influence on the structure of the fungal cell wall and/or the cell membrane. • The low cytotoxicity against erythrocytes and high lipophilicity of these derivatives are their additional good properties. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00253-021-11477-7. Springer Berlin Heidelberg 2021-08-19 2021 /pmc/articles/PMC8374424/ /pubmed/34410437 http://dx.doi.org/10.1007/s00253-021-11477-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Biotechnological Products and Process Engineering
Biernasiuk, Anna
Berecka-Rycerz, Anna
Gumieniczek, Anna
Malm, Maria
Łączkowski, Krzysztof Z.
Szymańska, Jolanta
Malm, Anna
The newly synthesized thiazole derivatives as potential antifungal compounds against Candida albicans
title The newly synthesized thiazole derivatives as potential antifungal compounds against Candida albicans
title_full The newly synthesized thiazole derivatives as potential antifungal compounds against Candida albicans
title_fullStr The newly synthesized thiazole derivatives as potential antifungal compounds against Candida albicans
title_full_unstemmed The newly synthesized thiazole derivatives as potential antifungal compounds against Candida albicans
title_short The newly synthesized thiazole derivatives as potential antifungal compounds against Candida albicans
title_sort newly synthesized thiazole derivatives as potential antifungal compounds against candida albicans
topic Biotechnological Products and Process Engineering
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374424/
https://www.ncbi.nlm.nih.gov/pubmed/34410437
http://dx.doi.org/10.1007/s00253-021-11477-7
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