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Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of Ferula huber-morathii Peşmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of Samarcandin

Ancient physicians frequently used the resin of Ferula species to treat cancer. Today, some folkloric recipes used for cancer treatment also contain the resin of Ferula species. The dichloromethane extract of the roots of Ferula huber-morathii exhibited cytotoxic activities against COLO 205 (colon),...

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Autores principales: Eruçar, Fatma Memnune, Kuran, Fadıl Kaan, Altıparmak Ülbegi, Gülsüm, Özbey, Süheyla, Karavuş, Şule Nur, Arcan, Gülşah Gamze, Yazıcı Tütüniş, Seçil, Tan, Nur, Aksoy Sağırlı, Pınar, Miski, Mahmut
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10305617/
https://www.ncbi.nlm.nih.gov/pubmed/37375740
http://dx.doi.org/10.3390/ph16060792
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author Eruçar, Fatma Memnune
Kuran, Fadıl Kaan
Altıparmak Ülbegi, Gülsüm
Özbey, Süheyla
Karavuş, Şule Nur
Arcan, Gülşah Gamze
Yazıcı Tütüniş, Seçil
Tan, Nur
Aksoy Sağırlı, Pınar
Miski, Mahmut
author_facet Eruçar, Fatma Memnune
Kuran, Fadıl Kaan
Altıparmak Ülbegi, Gülsüm
Özbey, Süheyla
Karavuş, Şule Nur
Arcan, Gülşah Gamze
Yazıcı Tütüniş, Seçil
Tan, Nur
Aksoy Sağırlı, Pınar
Miski, Mahmut
author_sort Eruçar, Fatma Memnune
collection PubMed
description Ancient physicians frequently used the resin of Ferula species to treat cancer. Today, some folkloric recipes used for cancer treatment also contain the resin of Ferula species. The dichloromethane extract of the roots of Ferula huber-morathii exhibited cytotoxic activities against COLO 205 (colon), K-562 (lymphoblast), and MCF-7 (breast) cancer cell lines (IC(50) = 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 F. huber-morathii using bioactivity-directed isolation studies. Extensive spectroscopic analyses and chemical transformations have elucidated the structures of these sesquiterpene coumarin ethers as conferone (1), conferol (2), feselol (3), badrakemone (4), mogoltadone (5), farnesiferol A (6), farnesiferol A acetate (7), gummosin (8), ferukrin (9), ferukrin acetate (10), deacetylkellerin (11), kellerin (12), samarcandone (13), samarcandin (14), and samarcandin acetate (15). The absolute configuration of samarcandin (14) was unequivocally determined by the X-ray crystallographic analysis of the semi-synthetic (R)-MTPA ester of samarcandin (24). Conferol (2) and mogoltadone (5) 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 (5) 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 (5) on cancer cell lines.
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spelling pubmed-103056172023-06-29 Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of Ferula huber-morathii Peşmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of Samarcandin Eruçar, Fatma Memnune Kuran, Fadıl Kaan Altıparmak Ülbegi, Gülsüm Özbey, Süheyla Karavuş, Şule Nur Arcan, Gülşah Gamze Yazıcı Tütüniş, Seçil Tan, Nur Aksoy Sağırlı, Pınar Miski, Mahmut Pharmaceuticals (Basel) Article Ancient physicians frequently used the resin of Ferula species to treat cancer. Today, some folkloric recipes used for cancer treatment also contain the resin of Ferula species. The dichloromethane extract of the roots of Ferula huber-morathii exhibited cytotoxic activities against COLO 205 (colon), K-562 (lymphoblast), and MCF-7 (breast) cancer cell lines (IC(50) = 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 F. huber-morathii using bioactivity-directed isolation studies. Extensive spectroscopic analyses and chemical transformations have elucidated the structures of these sesquiterpene coumarin ethers as conferone (1), conferol (2), feselol (3), badrakemone (4), mogoltadone (5), farnesiferol A (6), farnesiferol A acetate (7), gummosin (8), ferukrin (9), ferukrin acetate (10), deacetylkellerin (11), kellerin (12), samarcandone (13), samarcandin (14), and samarcandin acetate (15). The absolute configuration of samarcandin (14) was unequivocally determined by the X-ray crystallographic analysis of the semi-synthetic (R)-MTPA ester of samarcandin (24). Conferol (2) and mogoltadone (5) 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 (5) 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 (5) on cancer cell lines. MDPI 2023-05-26 /pmc/articles/PMC10305617/ /pubmed/37375740 http://dx.doi.org/10.3390/ph16060792 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Eruçar, Fatma Memnune
Kuran, Fadıl Kaan
Altıparmak Ülbegi, Gülsüm
Özbey, Süheyla
Karavuş, Şule Nur
Arcan, Gülşah Gamze
Yazıcı Tütüniş, Seçil
Tan, Nur
Aksoy Sağırlı, Pınar
Miski, Mahmut
Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of Ferula huber-morathii Peşmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of Samarcandin
title Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of Ferula huber-morathii Peşmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of Samarcandin
title_full Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of Ferula huber-morathii Peşmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of Samarcandin
title_fullStr Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of Ferula huber-morathii 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 Ferula huber-morathii Peşmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of Samarcandin
title_short Sesquiterpene Coumarin Ethers with Selective Cytotoxic Activities from the Roots of Ferula huber-morathii Peşmen (Apiaceae) and Unequivocal Determination of the Absolute Stereochemistry of Samarcandin
title_sort sesquiterpene coumarin ethers with selective cytotoxic activities from the roots of ferula huber-morathii peşmen (apiaceae) and unequivocal determination of the absolute stereochemistry of samarcandin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10305617/
https://www.ncbi.nlm.nih.gov/pubmed/37375740
http://dx.doi.org/10.3390/ph16060792
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