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 fif...
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MDPI AG
2019-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/24/4/666 |
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| author | Marcelina Mazur Witold Gładkowski Aleksandra Pawlak Bożena Obmińska-Mrukowicz Gabriela Maciejewska Czesław Wawrzeńczyk |
| author_facet | Marcelina Mazur Witold Gładkowski Aleksandra Pawlak Bożena Obmińska-Mrukowicz Gabriela Maciejewska Czesław Wawrzeńczyk |
| author_sort | Marcelina Mazur |
| collection | DOAJ |
| 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 (<i>Fusarium culmorum</i> AM10, <i>Armillaria mellea</i> AM296, <i>Trametes versicolor</i> 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 <i>Fusarium culmorum</i> AM10 introduced the hydroxy function at C-3 and C-4, <i>Armillaria mellea</i> AM296 incorporated the hydroxy function at C-3 and C-5 and <i>Trametes versicolor</i> 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<sub>50</sub> in the range 22.8⁻33.9 µg/mL). |
| first_indexed | 2024-12-10T21:26:49Z |
| format | Article |
| id | doaj.art-8ed518808d3043809e187d48f1278ac7 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-12-10T21:26:49Z |
| publishDate | 2019-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-8ed518808d3043809e187d48f1278ac72022-12-22T01:32:58ZengMDPI AGMolecules1420-30492019-02-0124466610.3390/molecules24040666molecules24040666Microbial Asymmetric Functionalization of β-Cyclocitral-Derived Tetramethyl-Substituted γ-LactoneMarcelina Mazur0Witold Gładkowski1Aleksandra Pawlak2Bożena Obmińska-Mrukowicz3Gabriela Maciejewska4Czesław Wawrzeńczyk5Department of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, PolandDepartment of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, PolandDepartment of Pharmacology and Toxicology, Wrocław University of Environmental and Life Sciences, Norwida 31, 50-375 Wrocław, PolandDepartment of Pharmacology and Toxicology, Wrocław University of Environmental and Life Sciences, Norwida 31, 50-375 Wrocław, PolandCentral Laboratory of the Instrumental Analysis, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, PolandDepartment of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, PolandSearching 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 (<i>Fusarium culmorum</i> AM10, <i>Armillaria mellea</i> AM296, <i>Trametes versicolor</i> 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 <i>Fusarium culmorum</i> AM10 introduced the hydroxy function at C-3 and C-4, <i>Armillaria mellea</i> AM296 incorporated the hydroxy function at C-3 and C-5 and <i>Trametes versicolor</i> 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<sub>50</sub> in the range 22.8⁻33.9 µg/mL).https://www.mdpi.com/1420-3049/24/4/666asymmetric hydroxylationantiproliferative activity<i>Fusarium culmorum</i><i>Armillaria mellea</i><i>Trametes versicolor</i> |
| spellingShingle | Marcelina Mazur Witold Gładkowski Aleksandra Pawlak Bożena Obmińska-Mrukowicz Gabriela Maciejewska Czesław Wawrzeńczyk Microbial Asymmetric Functionalization of β-Cyclocitral-Derived Tetramethyl-Substituted γ-Lactone Molecules asymmetric hydroxylation antiproliferative activity <i>Fusarium culmorum</i> <i>Armillaria mellea</i> <i>Trametes versicolor</i> |
| 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 | asymmetric hydroxylation antiproliferative activity <i>Fusarium culmorum</i> <i>Armillaria mellea</i> <i>Trametes versicolor</i> |
| url | https://www.mdpi.com/1420-3049/24/4/666 |
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