Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of <i>Ferula huber-morathii</i> Peşmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of Samarcandin
Ancient physicians frequently used the resin of <i>Ferula</i> species to treat cancer. Today, some folkloric recipes used for cancer treatment also contain the resin of <i>Ferula</i> species. The dichloromethane extract of the roots of <i>Ferula huber-morathii</i>...
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MDPI AG
2023-05-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/6/792 |
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| author | Fatma Memnune Eruçar Fadıl Kaan Kuran Gülsüm Altıparmak Ülbegi Süheyla Özbey Şule Nur Karavuş Gülşah Gamze Arcan Seçil Yazıcı Tütüniş Nur Tan Pınar Aksoy Sağırlı Mahmut Miski |
| author_facet | Fatma Memnune Eruçar Fadıl Kaan Kuran Gülsüm Altıparmak Ülbegi Süheyla Özbey Şule Nur Karavuş Gülşah Gamze Arcan Seçil Yazıcı Tütüniş Nur Tan Pınar Aksoy Sağırlı Mahmut Miski |
| author_sort | Fatma Memnune Eruçar |
| collection | DOAJ |
| description | Ancient physicians frequently used the resin of <i>Ferula</i> species to treat cancer. Today, some folkloric recipes used for cancer treatment also contain the resin of <i>Ferula</i> species. The dichloromethane extract of the roots of <i>Ferula huber-morathii</i> exhibited cytotoxic activities against COLO 205 (colon), K-562 (lymphoblast), and MCF-7 (breast) cancer cell lines (IC<sub>50</sub> = 52 µg/mL, 72 µg/mL, and 20 µg/mL, respectively). Fifteen sesquiterpene coumarin ethers with cytotoxic activity were isolated from the dichloromethane extract of the roots of <i>F. huber-morathii</i> using bioactivity-directed isolation studies. Extensive spectroscopic analyses and chemical transformations have elucidated the structures of these sesquiterpene coumarin ethers as conferone (<b>1</b>), conferol (<b>2</b>), feselol (<b>3</b>), badrakemone (<b>4</b>), mogoltadone (<b>5</b>), farnesiferol A (<b>6</b>), farnesiferol A acetate (<b>7</b>), gummosin (<b>8</b>), ferukrin (<b>9</b>), ferukrin acetate (<b>10</b>), deacetylkellerin (<b>11</b>), kellerin (<b>12</b>), samarcandone (<b>13</b>), samarcandin (<b>14</b>), and samarcandin acetate (<b>15</b>). The absolute configuration of samarcandin (<b>14</b>) was unequivocally determined by the X-ray crystallographic analysis of the semi-synthetic (<i>R</i>)-MTPA ester of samarcandin (<b>24</b>). Conferol (<b>2</b>) and mogoltadone (<b>5</b>) were found to be the most potent cytotoxic compounds against all three cancer cell lines; furthermore, these compounds exhibit low cytotoxic activity against the non-cancerous human umbilical vein epithelial cells (HUVEC) cell line. Investigation of the biological activity mechanisms of mogoltadone (<b>5</b>) revealed that while suppressing the levels of Bcl-XL and procaspase-3 in the COLO 205 cancer cell line, it did not have a significant effect on the Bcl-XL, caspase-3, and β-catenin protein levels of the HUVEC cell line, which may explain the cytotoxic selectivity of mogoltadone (<b>5</b>) on cancer cell lines. |
| first_indexed | 2024-03-11T02:03:27Z |
| format | Article |
| id | doaj.art-a5ab9fbd4c214586ad23017ea26436ec |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T02:03:27Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-a5ab9fbd4c214586ad23017ea26436ec2023-11-18T12:01:34ZengMDPI AGPharmaceuticals1424-82472023-05-0116679210.3390/ph16060792Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of <i>Ferula huber-morathii</i> Peşmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of SamarcandinFatma Memnune Eruçar0Fadıl Kaan Kuran1Gülsüm Altıparmak Ülbegi2Süheyla Özbey3Şule Nur Karavuş4Gülşah Gamze Arcan5Seçil Yazıcı Tütüniş6Nur Tan7Pınar Aksoy Sağırlı8Mahmut Miski9Department of Pharmacognosy, Faculty of Pharmacy, İstanbul University, 34116 İstanbul, TürkiyeDepartment of Pharmacognosy, Faculty of Pharmacy, İstanbul University, 34116 İstanbul, TürkiyeDepartment of Biochemistry, Faculty of Pharmacy, İstanbul University, 34116 İstanbul, TürkiyeDepartment of Engineering Physics, Faculty of Engineering, Hacettepe University, 06800 Ankara, TürkiyeDepartment of Pharmacognosy, School of Pharmacy, İstanbul Medipol University, 34810 İstanbul, TürkiyeDepartment of Biochemistry, Faculty of Pharmacy, İstanbul University, 34116 İstanbul, TürkiyeDepartment of Pharmacognosy, Faculty of Pharmacy, İstanbul University, 34116 İstanbul, TürkiyeDepartment of Pharmacognosy, Faculty of Pharmacy, İstanbul University, 34116 İstanbul, TürkiyeDepartment of Biochemistry, Faculty of Pharmacy, İstanbul University, 34116 İstanbul, TürkiyeDepartment of Pharmacognosy, Faculty of Pharmacy, İstanbul University, 34116 İstanbul, TürkiyeAncient physicians frequently used the resin of <i>Ferula</i> species to treat cancer. Today, some folkloric recipes used for cancer treatment also contain the resin of <i>Ferula</i> species. The dichloromethane extract of the roots of <i>Ferula huber-morathii</i> exhibited cytotoxic activities against COLO 205 (colon), K-562 (lymphoblast), and MCF-7 (breast) cancer cell lines (IC<sub>50</sub> = 52 µg/mL, 72 µg/mL, and 20 µg/mL, respectively). Fifteen sesquiterpene coumarin ethers with cytotoxic activity were isolated from the dichloromethane extract of the roots of <i>F. huber-morathii</i> using bioactivity-directed isolation studies. Extensive spectroscopic analyses and chemical transformations have elucidated the structures of these sesquiterpene coumarin ethers as conferone (<b>1</b>), conferol (<b>2</b>), feselol (<b>3</b>), badrakemone (<b>4</b>), mogoltadone (<b>5</b>), farnesiferol A (<b>6</b>), farnesiferol A acetate (<b>7</b>), gummosin (<b>8</b>), ferukrin (<b>9</b>), ferukrin acetate (<b>10</b>), deacetylkellerin (<b>11</b>), kellerin (<b>12</b>), samarcandone (<b>13</b>), samarcandin (<b>14</b>), and samarcandin acetate (<b>15</b>). The absolute configuration of samarcandin (<b>14</b>) was unequivocally determined by the X-ray crystallographic analysis of the semi-synthetic (<i>R</i>)-MTPA ester of samarcandin (<b>24</b>). Conferol (<b>2</b>) and mogoltadone (<b>5</b>) were found to be the most potent cytotoxic compounds against all three cancer cell lines; furthermore, these compounds exhibit low cytotoxic activity against the non-cancerous human umbilical vein epithelial cells (HUVEC) cell line. Investigation of the biological activity mechanisms of mogoltadone (<b>5</b>) revealed that while suppressing the levels of Bcl-XL and procaspase-3 in the COLO 205 cancer cell line, it did not have a significant effect on the Bcl-XL, caspase-3, and β-catenin protein levels of the HUVEC cell line, which may explain the cytotoxic selectivity of mogoltadone (<b>5</b>) on cancer cell lines.https://www.mdpi.com/1424-8247/16/6/792<i>Ferula huber-morathii</i>sesquiterpene coumarin etherscytotoxicityCOLO 205MCF-7K-562 |
| spellingShingle | Fatma Memnune Eruçar Fadıl Kaan Kuran Gülsüm Altıparmak Ülbegi Süheyla Özbey Şule Nur Karavuş Gülşah Gamze Arcan Seçil Yazıcı Tütüniş Nur Tan Pınar Aksoy Sağırlı Mahmut Miski Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of <i>Ferula huber-morathii</i> Peşmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of Samarcandin Pharmaceuticals <i>Ferula huber-morathii</i> sesquiterpene coumarin ethers cytotoxicity COLO 205 MCF-7 K-562 |
| title | Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of <i>Ferula huber-morathii</i> Peşmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of Samarcandin |
| title_full | Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of <i>Ferula huber-morathii</i> Peşmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of Samarcandin |
| title_fullStr | Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of <i>Ferula huber-morathii</i> Peşmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of Samarcandin |
| title_full_unstemmed | Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of <i>Ferula huber-morathii</i> Peşmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of Samarcandin |
| title_short | Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of <i>Ferula huber-morathii</i> Peşmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of Samarcandin |
| title_sort | sesquiterpene coumarin ethers with selective cytotoxic activities from the roots of i ferula huber morathii i pesmen apiaceae and unequivocal determination of the absolute stereochemistry of samarcandin |
| topic | <i>Ferula huber-morathii</i> sesquiterpene coumarin ethers cytotoxicity COLO 205 MCF-7 K-562 |
| url | https://www.mdpi.com/1424-8247/16/6/792 |
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