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

ABSTRACT: 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 (IC₅₀ = 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.

SUBMITTER: Erucar FM

PROVIDER: S-EPMC10305617 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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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.

Eruçar Fatma Memnune FM Kuran Fadıl Kaan FK Altıparmak Ülbegi Gülsüm G Özbey Süheyla S Karavuş Şule Nur ŞN Arcan Gülşah Gamze GG Yazıcı Tütüniş Seçil S Tan Nur N Aksoy Sağırlı Pınar P Miski Mahmut M

Pharmaceuticals (Basel, Switzerland) 20230526 6

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 (IC50 = 52 µg/mL, 72 µg/mL, and 20 µg/mL, respectively). Fifteen sesquiterpene coumarin ethers with cytotoxic ...[more]

PMID: 37375740

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Project description:Background and aimsStereochemical variation is widely known to influence the bioactivity of compounds in the context of pharmacology and pesticide science, but our understanding of its importance in mediating plant-herbivore interactions is limited, particularly in field settings. Similarly, sesquiterpene lactones are a broadly distributed class of putative defensive compounds, but little is known about their activities in the field.MethodsNatural variation in sesquiterpene lactones of the common cocklebur, Xanthium strumarium (Asteraceae), was used in conjunction with a series of common garden experiments to examine relationships between stereochemical variation, herbivore damage and plant fitness.Key resultsThe stereochemistry of sesquiterpene lactone ring junctions helped to explain variation in plant herbivore resistance. Plants producing cis-fused sesquiterpene lactones experienced significantly higher damage than plants producing trans-fused sesquiterpene lactones. Experiments manipulating herbivore damage above and below ambient levels found that herbivore damage was negatively correlated with plant fitness. This pattern translated into significant fitness differences between chemotypes under ambient levels of herbivore attack, but not when attack was experimentally reduced via pesticide.ConclusionsTo our knowledge, this work represents only the second study to examine sesquiterpene lactones as defensive compounds in the field, the first to document herbivore-mediated natural selection on sesquiterpene lactone variation and the first to investigate the ecological significance of the stereochemistry of the lactone ring junction. The results indicate that subtle differences in stereochemistry may be a major determinant of the protective role of secondary metabolites and thus of plant fitness. As stereochemical variation is widespread in many groups of secondary metabolites, these findings suggest the possibility of dynamic evolutionary histories within the Asteraceae and other plant families showing extensive stereochemical variation.

Dataset Information

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

Publications

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.

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