Seven previously undescribed sesquiterpene lactones, three known sesquiterpene lactones (ixerin D, 15-p-hydroxyphenylacetyllactucin, and 15-p-hydroxyphenylacetyllactucin-8-sulfate), and two known quinic acid derivatives (3-O-feruloylquinic acid and 3,5-di-O-caffeoylquinic acid) were isolated from Sonchus palustris L. roots. Four formerly undescribed compounds were elucidated to be 3β,14-dihydroxycostunolide-3-O-β-D-glucopyranosyl-(2-O-p-hydroxyphenylacetyl)-14-O-p-hydroxyphenylacetate, 15-p-methoxyphenylacetyllactucin, 15-p-methoxyphenylacetyllactucin-8-sulfate, and 8-p-hydroxyphenylacetyllactucin-15-sulfate. Additionally, three undescribed conjugates of lactucin and a eudesmanolide type sesquiterpenic acid, sonchpalustrin, 4″-O-methylsonchpalustrin, and isosonchpalustrin, were characterized. The structures of the newly discovered natural products were elucidated using 1D and 2D NMR spectroscopy and UHPLC-HRMS. 15-p-Hydroxyphenylacetyllactucin and 15-p-methoxyphenylacetyllactucin showed significant in vitro cytotoxicity against CEM and BJ cells with IC50 values ranging from 3.9 to 9.8 μM. Compounds 3 and 4 showed also strong anti-inflammatory activity in vitro.
- MeSH
- Asteraceae chemie MeSH
- fytogenní protinádorové látky chemie izolace a purifikace farmakologie MeSH
- fytonutrienty chemie izolace a purifikace farmakologie MeSH
- kultivované buňky MeSH
- laktony chemie izolace a purifikace farmakologie MeSH
- lidé MeSH
- proliferace buněk účinky léků MeSH
- screeningové testy protinádorových léčiv MeSH
- seskviterpeny chemie izolace a purifikace farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
This paper describes the synthesis of a new A-homo lactam D-homo lactone androstane derivative from dehydroepiandrosterone. To evaluate the impact of the introduction of nitrogen in the parental scaffold on biological activity, a new androstane enamide-type lactam derivative was prepared and characterized. The new compound as well as starting compounds were screened for cytotoxic, anti-angiogenic and anti-inflammatory activities using several human cancer cell lines (MCF-7, MDA-MB-231, PC3, CEM, G-361, HeLa), endothelial (HUVEC) and non-tumour (MRC-5 and BJ) cell lines. Strong cytotoxic and anti-inflammatory activity with a broad therapeutical window was demonstrated by the A-homo lactam D-homo lactone androstane derivative. The induction of apoptosis in treated PC3 cultures was confirmed using apoptotic morphology screening and a fluorescent double-staining method. New A-homo lactam D-homo lactone androstane derivative induced apoptosis more than the tested reference compounds, Formestane and Doxorubicin. An in silico ADME analysis showed that the compounds possess drug-like properties.
- MeSH
- androstany chemie izolace a purifikace farmakologie MeSH
- antiflogistika chemie izolace a purifikace farmakologie MeSH
- apoptóza účinky léků MeSH
- E-selektin antagonisté a inhibitory biosyntéza MeSH
- fytogenní protinádorové látky chemie izolace a purifikace farmakologie MeSH
- kultivované buňky MeSH
- laktony chemie izolace a purifikace farmakologie MeSH
- lidé MeSH
- molekulární konformace MeSH
- optické zobrazování MeSH
- proliferace buněk účinky léků MeSH
- screeningové testy protinádorových léčiv MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Actinomycete strain YIM PH20520, isolated from the rhizosphere soil sample of Panax notoginseng collected in Wenshang, Yunnan Province, China, exhibited antifungal activity against root-rot pathogens of the Panax notoginseng. The structures of bioactive molecules, isolated from the ethyl acetate extract of the fermentation broth of the strain, were identified as echinosporin (1) and 7-deoxyechinosporin (2) based on extensive spectroscopic analyses. 1 exhibited antifungal activity against four tested root-rot pathogens of Panax notoginseng include Fusarium oxysporum, Fusarium solani, Alternaria panax, and Phoma herbarum with the MIC value at 64, 64, 32, and 64 μg/mL, respectively. 2 exhibited antifungal activities against F. oxysporum, F. solani, A. panax, and P. herbarum with the MIC value at 128, 128, 64, and 128 μg/mL, respectively. Based on the phylogenetic analyses, the closest phylogenetic relative of strain YIM PH20520 is Amycolatopsis speibonae JS72T (97.69%), so strain YIM PH20520 was identified as Amycolatopsis strain. To the best of our knowledge, this is the first report of echinosporin antibiotics isolated from Amycolatopsis strain besides Streptomyces strain and their antifungal activity against four tested root-rot pathogens of the Panax notoginseng. The results provide a reliable evidence for the following related biosynthetic investigations on Amycolatopsis strain YIM PH20520 due to echinosporins antibiotics' unique tricyclic acetal-lactone structures.
- MeSH
- Actinobacteria chemie klasifikace genetika MeSH
- antifungální látky chemie izolace a purifikace farmakologie MeSH
- fylogeneze MeSH
- houby účinky léků MeSH
- kořeny rostlin mikrobiologie MeSH
- laktony chemie izolace a purifikace farmakologie MeSH
- mikrobiální testy citlivosti MeSH
- molekulární struktura MeSH
- nemoci rostlin mikrobiologie MeSH
- Panax notoginseng mikrobiologie MeSH
- rhizosféra MeSH
- RNA ribozomální 16S genetika MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Čína MeSH
Three new and five known sesquiterpene lactones were isolated from the roots of Laser trilobum (L.) Borkh. Chemical identity of the known compounds and structural analysis of the new ones were determined by HR MS and NMR spectroscopy. The two new sesquiterpene lactones: 2-acetoxytrilobolide and 2-hydroxy-10-deacetyltrilobolide belong to the guaianolide type, and the third one, eudeslaserolide, to the biogenetically related eudesmanolide type. Both types, together with their biogenetic precursor of germacranolide type (laserolide) are present in L. trilobum, as well as in the related Laserpitium species. Purposefully selected set of these native sesquiterpene lactones was tested for specific immunobiological properties. The obtained results demonstrate that trilobolide and its acetoxy analog are strong activators of cytokine secretion. On the contrary, the other L. trilobum and Laserpitium siler constituents are only very mild activators, or even inhibitors of the cytokine and nitric oxide production.
- MeSH
- adjuvancia imunologická izolace a purifikace farmakologie MeSH
- Apiaceae chemie MeSH
- butyráty izolace a purifikace farmakologie MeSH
- cytokiny sekrece MeSH
- furany izolace a purifikace farmakologie MeSH
- kořeny rostlin chemie MeSH
- krysa rodu rattus MeSH
- laktony izolace a purifikace farmakologie MeSH
- molekulární struktura MeSH
- oxid dusnatý biosyntéza MeSH
- potkani Wistar MeSH
- rostlinné extrakty chemie farmakologie MeSH
- seskviterpeny izolace a purifikace farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- theonellapeptolidy,
- MeSH
- cyklické peptidy * chemie izolace a purifikace MeSH
- fertilizace účinky léků MeSH
- klinická chemie metody trendy MeSH
- laktony * chemie izolace a purifikace MeSH
- motilita spermií účinky léků MeSH
- protinádorové látky MeSH
- rostlinné přípravky terapeutické užití MeSH
- Theonella chemie MeSH
