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Photosensitive and pH-dependent activity of pyrazine-functionalized carbazole derivative as promising antifungal and imaging agent

Carbazole skeleton plays a significant role as a structural scaffold of many pharmacologically active compounds. Pyrazine-functionalized carbazole derivative was constructed by coupling 2-amino-5-bromo-3-methylaminepyrazine (ABMAP) into 3 and 6 positions of the carbazole ring. Multi-experimental met...

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Autores principales: Chylewska, Agnieszka, Dąbrowska, Aleksandra M., Ramotowska, Sandra, Maciejewska, Natalia, Olszewski, Mateusz, Bagiński, Maciej, Makowski, Mariusz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367338/
https://www.ncbi.nlm.nih.gov/pubmed/32678219
http://dx.doi.org/10.1038/s41598-020-68758-w
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author Chylewska, Agnieszka
Dąbrowska, Aleksandra M.
Ramotowska, Sandra
Maciejewska, Natalia
Olszewski, Mateusz
Bagiński, Maciej
Makowski, Mariusz
author_facet Chylewska, Agnieszka
Dąbrowska, Aleksandra M.
Ramotowska, Sandra
Maciejewska, Natalia
Olszewski, Mateusz
Bagiński, Maciej
Makowski, Mariusz
author_sort Chylewska, Agnieszka
collection PubMed
description Carbazole skeleton plays a significant role as a structural scaffold of many pharmacologically active compounds. Pyrazine-functionalized carbazole derivative was constructed by coupling 2-amino-5-bromo-3-methylaminepyrazine (ABMAP) into 3 and 6 positions of the carbazole ring. Multi-experimental methods were used, e.g., potentiometric, spectroscopic (ATR, UV, XRD powder,(1)H and(13)C NMR), electrochemical (cyclic voltammetry), and optical techniques, to receive the complete structural analysis, physicochemical (pKa, logP) and biological profile of a new carbazole derivative with acronym 3,6-PIRAMICAR. The interaction ability of the compound studied with potential cellular targets like Calf Thymus DNA (CT-DNA), or Bovine Serum Albumin (BSA) were also taken into account. Experiments showed the existence of strong binding, but no DNA or BSA cleavage was observed. The comparative analyzes of compounds anti-Candida action clearly show pH-dependent antifungal activity of 3,6-PIRAMICAR, which was strongly stimulated in the acidic media. Surprisingly, the titled compound turn out to be much more effective (14 times by MIC50; 8 times by MIC; c.a. 4 times by MFC) against Candida krusei than fluconazole at pH 4.
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spelling pubmed-73673382020-07-20 Photosensitive and pH-dependent activity of pyrazine-functionalized carbazole derivative as promising antifungal and imaging agent Chylewska, Agnieszka Dąbrowska, Aleksandra M. Ramotowska, Sandra Maciejewska, Natalia Olszewski, Mateusz Bagiński, Maciej Makowski, Mariusz Sci Rep Article Carbazole skeleton plays a significant role as a structural scaffold of many pharmacologically active compounds. Pyrazine-functionalized carbazole derivative was constructed by coupling 2-amino-5-bromo-3-methylaminepyrazine (ABMAP) into 3 and 6 positions of the carbazole ring. Multi-experimental methods were used, e.g., potentiometric, spectroscopic (ATR, UV, XRD powder,(1)H and(13)C NMR), electrochemical (cyclic voltammetry), and optical techniques, to receive the complete structural analysis, physicochemical (pKa, logP) and biological profile of a new carbazole derivative with acronym 3,6-PIRAMICAR. The interaction ability of the compound studied with potential cellular targets like Calf Thymus DNA (CT-DNA), or Bovine Serum Albumin (BSA) were also taken into account. Experiments showed the existence of strong binding, but no DNA or BSA cleavage was observed. The comparative analyzes of compounds anti-Candida action clearly show pH-dependent antifungal activity of 3,6-PIRAMICAR, which was strongly stimulated in the acidic media. Surprisingly, the titled compound turn out to be much more effective (14 times by MIC50; 8 times by MIC; c.a. 4 times by MFC) against Candida krusei than fluconazole at pH 4. Nature Publishing Group UK 2020-07-16 /pmc/articles/PMC7367338/ /pubmed/32678219 http://dx.doi.org/10.1038/s41598-020-68758-w Text en © The Author(s) 2020 Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Chylewska, Agnieszka
Dąbrowska, Aleksandra M.
Ramotowska, Sandra
Maciejewska, Natalia
Olszewski, Mateusz
Bagiński, Maciej
Makowski, Mariusz
Photosensitive and pH-dependent activity of pyrazine-functionalized carbazole derivative as promising antifungal and imaging agent
title Photosensitive and pH-dependent activity of pyrazine-functionalized carbazole derivative as promising antifungal and imaging agent
title_full Photosensitive and pH-dependent activity of pyrazine-functionalized carbazole derivative as promising antifungal and imaging agent
title_fullStr Photosensitive and pH-dependent activity of pyrazine-functionalized carbazole derivative as promising antifungal and imaging agent
title_full_unstemmed Photosensitive and pH-dependent activity of pyrazine-functionalized carbazole derivative as promising antifungal and imaging agent
title_short Photosensitive and pH-dependent activity of pyrazine-functionalized carbazole derivative as promising antifungal and imaging agent
title_sort photosensitive and ph-dependent activity of pyrazine-functionalized carbazole derivative as promising antifungal and imaging agent
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367338/
https://www.ncbi.nlm.nih.gov/pubmed/32678219
http://dx.doi.org/10.1038/s41598-020-68758-w
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