Unique Phenanthrenes from <i>Juncus ensifolius</i> and Their Antiproliferative and Synergistic Effects with the Conventional Anticancer Agent Doxorubicin against Human Cancer Cell Lines
Phenanthrenes are the main special metabolites of Juncaceae species from phytochemical, pharmacological, and chemotaxonomical points of view. The present study focused on the isolation, structure determination, and pharmacological investigation of phenanthrenes from <i>Juncus ensifolius</i&...
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2022-03-01
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| author | Dóra Stefkó Norbert Kúsz Nikoletta Szemerédi Anita Barta Gabriella Spengler Róbert Berkecz Judit Hohmann Andrea Vasas |
| author_facet | Dóra Stefkó Norbert Kúsz Nikoletta Szemerédi Anita Barta Gabriella Spengler Róbert Berkecz Judit Hohmann Andrea Vasas |
| author_sort | Dóra Stefkó |
| collection | DOAJ |
| description | Phenanthrenes are the main special metabolites of Juncaceae species from phytochemical, pharmacological, and chemotaxonomical points of view. The present study focused on the isolation, structure determination, and pharmacological investigation of phenanthrenes from <i>Juncus ensifolius</i>. Nineteen compounds, including 17 phenanthrenes, were identified from the methanol extract of the plant. Thirteen compounds, namely, ensifolins A–M (<b>1</b>–<b>13</b>), were obtained for the first time from natural sources. Four phenanthrenes [2-hydroxy-1,7-dimethyl-5-vinyl-9,10-dihydrophenanthrene (<b>14</b>), juncuenin B (<b>15</b>), juncatrin B (<b>16</b>), and sylvaticin A (<b>17</b>)], 4-hydroxybenzaldehyde (<b>18</b>) and luteolin (<b>19</b>) were isolated for the first time from <i>J. ensifolius</i>. Ensifolins A (<b>1</b>) and B (<b>2</b>) are structurally unique phenanthrenes, considering that they are flavonoid- (<b>1</b>) or benzaldehyde-adducts (<b>2</b>). The antiproliferative activity of all isolated compounds against HeLa, COLO 205, and COLO 320 cancer cells and a non-tumor (MRC-5) cell line was tested using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) viability assay. The luteolin-substituted phenanthrene ensifolin A (<b>1</b>) proved to be the most active against all three cancer cell lines (IC<sub>50</sub> values 3.9–12.7 μM) and showed good selectivity (SI = 4.95) in the case of COLO 205. The best selectivity was recorded for ensifolins D (<b>4</b>, SI > 5.15, HeLa), H (<b>8</b>, SI > 8.13, HeLa), and <b>17</b> (SI > 9.43, HeLa). The synergistic activity of the compounds with doxorubicin was also tested on HeLa cells, and ensifolins E (<b>5</b>) and H (<b>8</b>) exhibited very strong synergism (CI < 0.1). In conclusion, these phenanthrenes are worthy of further investigation. |
| first_indexed | 2024-03-09T12:58:51Z |
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| spelling | doaj.art-7308c4ce208146b1a2bc1169bf62ac822023-11-30T21:57:20ZengMDPI AGPharmaceutics1999-49232022-03-0114360810.3390/pharmaceutics14030608Unique Phenanthrenes from <i>Juncus ensifolius</i> and Their Antiproliferative and Synergistic Effects with the Conventional Anticancer Agent Doxorubicin against Human Cancer Cell LinesDóra Stefkó0Norbert Kúsz1Nikoletta Szemerédi2Anita Barta3Gabriella Spengler4Róbert Berkecz5Judit Hohmann6Andrea Vasas7Department of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, 6720 Szeged, HungaryDepartment of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, 6720 Szeged, HungaryDepartment of Medical Microbiology, Albert Szent-Györgyi Health Center, Albert Szent-Györgyi Medical School, University of Szeged, 6725 Szeged, HungaryDepartment of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, 6720 Szeged, HungaryDepartment of Medical Microbiology, Albert Szent-Györgyi Health Center, Albert Szent-Györgyi Medical School, University of Szeged, 6725 Szeged, HungaryInstitute of Pharmaceutical Analysis, University of Szeged, 6720 Szeged, HungaryDepartment of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, 6720 Szeged, HungaryDepartment of Pharmacognosy, Interdisciplinary Excellence Centre, University of Szeged, 6720 Szeged, HungaryPhenanthrenes are the main special metabolites of Juncaceae species from phytochemical, pharmacological, and chemotaxonomical points of view. The present study focused on the isolation, structure determination, and pharmacological investigation of phenanthrenes from <i>Juncus ensifolius</i>. Nineteen compounds, including 17 phenanthrenes, were identified from the methanol extract of the plant. Thirteen compounds, namely, ensifolins A–M (<b>1</b>–<b>13</b>), were obtained for the first time from natural sources. Four phenanthrenes [2-hydroxy-1,7-dimethyl-5-vinyl-9,10-dihydrophenanthrene (<b>14</b>), juncuenin B (<b>15</b>), juncatrin B (<b>16</b>), and sylvaticin A (<b>17</b>)], 4-hydroxybenzaldehyde (<b>18</b>) and luteolin (<b>19</b>) were isolated for the first time from <i>J. ensifolius</i>. Ensifolins A (<b>1</b>) and B (<b>2</b>) are structurally unique phenanthrenes, considering that they are flavonoid- (<b>1</b>) or benzaldehyde-adducts (<b>2</b>). The antiproliferative activity of all isolated compounds against HeLa, COLO 205, and COLO 320 cancer cells and a non-tumor (MRC-5) cell line was tested using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) viability assay. The luteolin-substituted phenanthrene ensifolin A (<b>1</b>) proved to be the most active against all three cancer cell lines (IC<sub>50</sub> values 3.9–12.7 μM) and showed good selectivity (SI = 4.95) in the case of COLO 205. The best selectivity was recorded for ensifolins D (<b>4</b>, SI > 5.15, HeLa), H (<b>8</b>, SI > 8.13, HeLa), and <b>17</b> (SI > 9.43, HeLa). The synergistic activity of the compounds with doxorubicin was also tested on HeLa cells, and ensifolins E (<b>5</b>) and H (<b>8</b>) exhibited very strong synergism (CI < 0.1). In conclusion, these phenanthrenes are worthy of further investigation.https://www.mdpi.com/1999-4923/14/3/608<i>Juncus ensifolius</i>Juncaceaephenanthreneantiproliferativedoxorubicincombination assay |
| spellingShingle | Dóra Stefkó Norbert Kúsz Nikoletta Szemerédi Anita Barta Gabriella Spengler Róbert Berkecz Judit Hohmann Andrea Vasas Unique Phenanthrenes from <i>Juncus ensifolius</i> and Their Antiproliferative and Synergistic Effects with the Conventional Anticancer Agent Doxorubicin against Human Cancer Cell Lines Pharmaceutics <i>Juncus ensifolius</i> Juncaceae phenanthrene antiproliferative doxorubicin combination assay |
| title | Unique Phenanthrenes from <i>Juncus ensifolius</i> and Their Antiproliferative and Synergistic Effects with the Conventional Anticancer Agent Doxorubicin against Human Cancer Cell Lines |
| title_full | Unique Phenanthrenes from <i>Juncus ensifolius</i> and Their Antiproliferative and Synergistic Effects with the Conventional Anticancer Agent Doxorubicin against Human Cancer Cell Lines |
| title_fullStr | Unique Phenanthrenes from <i>Juncus ensifolius</i> and Their Antiproliferative and Synergistic Effects with the Conventional Anticancer Agent Doxorubicin against Human Cancer Cell Lines |
| title_full_unstemmed | Unique Phenanthrenes from <i>Juncus ensifolius</i> and Their Antiproliferative and Synergistic Effects with the Conventional Anticancer Agent Doxorubicin against Human Cancer Cell Lines |
| title_short | Unique Phenanthrenes from <i>Juncus ensifolius</i> and Their Antiproliferative and Synergistic Effects with the Conventional Anticancer Agent Doxorubicin against Human Cancer Cell Lines |
| title_sort | unique phenanthrenes from i juncus ensifolius i and their antiproliferative and synergistic effects with the conventional anticancer agent doxorubicin against human cancer cell lines |
| topic | <i>Juncus ensifolius</i> Juncaceae phenanthrene antiproliferative doxorubicin combination assay |
| url | https://www.mdpi.com/1999-4923/14/3/608 |
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