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Novel 2,4-Disubstituted-1,3-Thiazole Derivatives: Synthesis, Anti-Candida Activity Evaluation and Interaction with Bovine Serum Albumine
Herein we report the synthesis of two novel series of 1,3-thiazole derivatives having a lipophilic C4-substituent on account of the increasing need for novel and versatile antifungal drugs for the treatment of resistant Candida sp.-based infections. Following their structural characterization, the a...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179180/ https://www.ncbi.nlm.nih.gov/pubmed/32121062 http://dx.doi.org/10.3390/molecules25051079 |
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author | Pricopie, Andreea-Iulia Focșan, Monica Ionuț, Ioana Marc, Gabriel Vlase, Laurian Găină, Luiza-Ioana Vodnar, Dan C. Simon, Elemer Barta, Gabriel Pîrnău, Adrian Oniga, Ovidiu |
author_facet | Pricopie, Andreea-Iulia Focșan, Monica Ionuț, Ioana Marc, Gabriel Vlase, Laurian Găină, Luiza-Ioana Vodnar, Dan C. Simon, Elemer Barta, Gabriel Pîrnău, Adrian Oniga, Ovidiu |
author_sort | Pricopie, Andreea-Iulia |
collection | PubMed |
description | Herein we report the synthesis of two novel series of 1,3-thiazole derivatives having a lipophilic C4-substituent on account of the increasing need for novel and versatile antifungal drugs for the treatment of resistant Candida sp.-based infections. Following their structural characterization, the anti-Candida activity was evaluated in vitro while using the broth microdilution method. Three compounds exhibited lower Minimum Inhibitory Concentration (MIC) values when compared to fluconazole, being used as the reference antifungal drug. An in silico molecular docking study was subsequently carried out in order to gain more insight into the antifungal mechanism of action, while using lanosterol-C14α-demethylase as the target enzyme. Fluorescence microscopy was employed to further investigate the cellular target of the most promising molecule, with the obtained results confirming its damaging effect towards the fungal cell membrane integrity. Finally, the distribution and the pharmacological potential in vivo of the novel thiazole derivatives was investigated through the study of their binding interaction with bovine serum albumin, while using fluorescence spectroscopy. |
format | Online Article Text |
id | pubmed-7179180 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71791802020-04-28 Novel 2,4-Disubstituted-1,3-Thiazole Derivatives: Synthesis, Anti-Candida Activity Evaluation and Interaction with Bovine Serum Albumine Pricopie, Andreea-Iulia Focșan, Monica Ionuț, Ioana Marc, Gabriel Vlase, Laurian Găină, Luiza-Ioana Vodnar, Dan C. Simon, Elemer Barta, Gabriel Pîrnău, Adrian Oniga, Ovidiu Molecules Article Herein we report the synthesis of two novel series of 1,3-thiazole derivatives having a lipophilic C4-substituent on account of the increasing need for novel and versatile antifungal drugs for the treatment of resistant Candida sp.-based infections. Following their structural characterization, the anti-Candida activity was evaluated in vitro while using the broth microdilution method. Three compounds exhibited lower Minimum Inhibitory Concentration (MIC) values when compared to fluconazole, being used as the reference antifungal drug. An in silico molecular docking study was subsequently carried out in order to gain more insight into the antifungal mechanism of action, while using lanosterol-C14α-demethylase as the target enzyme. Fluorescence microscopy was employed to further investigate the cellular target of the most promising molecule, with the obtained results confirming its damaging effect towards the fungal cell membrane integrity. Finally, the distribution and the pharmacological potential in vivo of the novel thiazole derivatives was investigated through the study of their binding interaction with bovine serum albumin, while using fluorescence spectroscopy. MDPI 2020-02-28 /pmc/articles/PMC7179180/ /pubmed/32121062 http://dx.doi.org/10.3390/molecules25051079 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Pricopie, Andreea-Iulia Focșan, Monica Ionuț, Ioana Marc, Gabriel Vlase, Laurian Găină, Luiza-Ioana Vodnar, Dan C. Simon, Elemer Barta, Gabriel Pîrnău, Adrian Oniga, Ovidiu Novel 2,4-Disubstituted-1,3-Thiazole Derivatives: Synthesis, Anti-Candida Activity Evaluation and Interaction with Bovine Serum Albumine |
title | Novel 2,4-Disubstituted-1,3-Thiazole Derivatives: Synthesis, Anti-Candida Activity Evaluation and Interaction with Bovine Serum Albumine |
title_full | Novel 2,4-Disubstituted-1,3-Thiazole Derivatives: Synthesis, Anti-Candida Activity Evaluation and Interaction with Bovine Serum Albumine |
title_fullStr | Novel 2,4-Disubstituted-1,3-Thiazole Derivatives: Synthesis, Anti-Candida Activity Evaluation and Interaction with Bovine Serum Albumine |
title_full_unstemmed | Novel 2,4-Disubstituted-1,3-Thiazole Derivatives: Synthesis, Anti-Candida Activity Evaluation and Interaction with Bovine Serum Albumine |
title_short | Novel 2,4-Disubstituted-1,3-Thiazole Derivatives: Synthesis, Anti-Candida Activity Evaluation and Interaction with Bovine Serum Albumine |
title_sort | novel 2,4-disubstituted-1,3-thiazole derivatives: synthesis, anti-candida activity evaluation and interaction with bovine serum albumine |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179180/ https://www.ncbi.nlm.nih.gov/pubmed/32121062 http://dx.doi.org/10.3390/molecules25051079 |
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