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Microbial Asymmetric Functionalization of β-Cyclocitral-Derived Tetramethyl-Substituted γ-Lactone
Searching for the new anticancer compounds we prepared three new β-cyclocitral-derived hydroxyl-γ-lactones by microbial hydroxylation of tetramethyl-substituted bicyclic γ-lactone. The substrate was transformed by the enzymatic system of filamentous fungi. Three out of fifteen strains were selected...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412764/ https://www.ncbi.nlm.nih.gov/pubmed/30781874 http://dx.doi.org/10.3390/molecules24040666 |
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author | Mazur, Marcelina Gładkowski, Witold Pawlak, Aleksandra Obmińska-Mrukowicz, Bożena Maciejewska, Gabriela Wawrzeńczyk, Czesław |
author_facet | Mazur, Marcelina Gładkowski, Witold Pawlak, Aleksandra Obmińska-Mrukowicz, Bożena Maciejewska, Gabriela Wawrzeńczyk, Czesław |
author_sort | Mazur, Marcelina |
collection | PubMed |
description | Searching for the new anticancer compounds we prepared three new β-cyclocitral-derived hydroxyl-γ-lactones by microbial hydroxylation of tetramethyl-substituted bicyclic γ-lactone. The substrate was transformed by the enzymatic system of filamentous fungi. Three out of fifteen strains were selected as effective biocatalysts (Fusarium culmorum AM10, Armillaria mellea AM296, Trametes versicolor AM536). The hydroxylation processes were not only regioselective but also stereoselective. The hydroxylation products of each secondary carbon atom in the cyclohexane ring were obtained by the application of the selected fungal strains. The Fusarium culmorum AM10 introduced the hydroxy function at C-3 and C-4, Armillaria mellea AM296 incorporated the hydroxy function at C-3 and C-5 and Trametes versicolor AM536 transformed the substrate to the mixture of C-3, C-4 and C-5 hydroxylactones. The hydroxylactones obtained were enantiomericaly enriched (ee values in the range 17–99%). The in vitro antiproliferative activities of the functionalization products were also evaluated. Regardless of the hydroxy substituent location all tested lactones exhibited similar, significant activity towards selected cancer cell lines (IC(50) in the range 22.8–33.9 µg/mL). |
format | Online Article Text |
id | pubmed-6412764 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-64127642019-04-09 Microbial Asymmetric Functionalization of β-Cyclocitral-Derived Tetramethyl-Substituted γ-Lactone Mazur, Marcelina Gładkowski, Witold Pawlak, Aleksandra Obmińska-Mrukowicz, Bożena Maciejewska, Gabriela Wawrzeńczyk, Czesław Molecules Article Searching for the new anticancer compounds we prepared three new β-cyclocitral-derived hydroxyl-γ-lactones by microbial hydroxylation of tetramethyl-substituted bicyclic γ-lactone. The substrate was transformed by the enzymatic system of filamentous fungi. Three out of fifteen strains were selected as effective biocatalysts (Fusarium culmorum AM10, Armillaria mellea AM296, Trametes versicolor AM536). The hydroxylation processes were not only regioselective but also stereoselective. The hydroxylation products of each secondary carbon atom in the cyclohexane ring were obtained by the application of the selected fungal strains. The Fusarium culmorum AM10 introduced the hydroxy function at C-3 and C-4, Armillaria mellea AM296 incorporated the hydroxy function at C-3 and C-5 and Trametes versicolor AM536 transformed the substrate to the mixture of C-3, C-4 and C-5 hydroxylactones. The hydroxylactones obtained were enantiomericaly enriched (ee values in the range 17–99%). The in vitro antiproliferative activities of the functionalization products were also evaluated. Regardless of the hydroxy substituent location all tested lactones exhibited similar, significant activity towards selected cancer cell lines (IC(50) in the range 22.8–33.9 µg/mL). MDPI 2019-02-13 /pmc/articles/PMC6412764/ /pubmed/30781874 http://dx.doi.org/10.3390/molecules24040666 Text en © 2019 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 Mazur, Marcelina Gładkowski, Witold Pawlak, Aleksandra Obmińska-Mrukowicz, Bożena Maciejewska, Gabriela Wawrzeńczyk, Czesław Microbial Asymmetric Functionalization of β-Cyclocitral-Derived Tetramethyl-Substituted γ-Lactone |
title | Microbial Asymmetric Functionalization of β-Cyclocitral-Derived Tetramethyl-Substituted γ-Lactone |
title_full | Microbial Asymmetric Functionalization of β-Cyclocitral-Derived Tetramethyl-Substituted γ-Lactone |
title_fullStr | Microbial Asymmetric Functionalization of β-Cyclocitral-Derived Tetramethyl-Substituted γ-Lactone |
title_full_unstemmed | Microbial Asymmetric Functionalization of β-Cyclocitral-Derived Tetramethyl-Substituted γ-Lactone |
title_short | Microbial Asymmetric Functionalization of β-Cyclocitral-Derived Tetramethyl-Substituted γ-Lactone |
title_sort | microbial asymmetric functionalization of β-cyclocitral-derived tetramethyl-substituted γ-lactone |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6412764/ https://www.ncbi.nlm.nih.gov/pubmed/30781874 http://dx.doi.org/10.3390/molecules24040666 |
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