Linseed represents a rich source of nutritional, functional and health-beneficial compounds. Nevertheless, the chemical composition and content of bioactive compounds may be quite variable and potentially affected by various factors, including genotype and the environment. In this study, the proximate chemical composition, lignans content and antioxidant potential of six experimentally grown linseed cultivars were assessed and compared. A diagonal cultivation trial in the University of South Bohemia Experimental Station in České Budějovice, Czech Republic, was established in three subsequent growing seasons (2018, 2019 and 2020). The results showed that the cultivar and growing conditions influenced most studied parameters. The lack of precipitation in May and June 2019 negatively affected the seed yield and the level of secoisolariciresinol diglucoside but did not decrease the crude protein content, which was negatively related to the oil content. The newly developed method for lignans analysis allowed the identification and quantification of secoisolariciresinol diglucoside and matairesinol. Their content correlated positively with the total polyphenol content and antioxidant assays (DPPH and ABTS radical scavenging activity), indicating the significant contribution to the biofunctional properties of linseed. On the other hand, we did not detect minor linseed lignans, pinoresinol and lariciresinol. The results of this study showed the importance of cultivar and growing conditions factors on the linseed chemical composition and the lignans content, determining its nutritional and medicinal properties.
This review summarizes our work in the field of syn-thesis of natural products and their derivatives. Applica-tion of modern synthetic method is discussed in the con-text of the syntheses of both enantiomers of hydromor-phone, (–)-tetrodotoxin (a marine toxin), and selaginpul-vilins C and D (natural fluorene derivatives). Further, syn-thesis of notoincisol A, selagibenzophenones A and B is described to clarify the structural aspects of the com-pounds. Last but not least, synthesis and pharmaceutical profilation of derivatives of magnolol and honokiol is dis-cussed as well.Fulltext of this article is available on the website of this Journal.
- MeSH
- alkyny chemická syntéza chemie MeSH
- biologické přípravky MeSH
- hydromorfon chemická syntéza chemie farmakologie MeSH
- lidé MeSH
- lignany chemická syntéza chemie MeSH
- polyacetyleny chemická syntéza chemie MeSH
- polycyklické sloučeniny chemická syntéza chemie MeSH
- Selaginellaceae chemie MeSH
- techniky syntetické chemie * metody MeSH
- tetrodotoxin chemická syntéza chemie farmakologie MeSH
- vyvíjení léků MeSH
- Check Tag
- lidé MeSH
Lignans and neolignans are plant secondary metabolites derived from the oxidative coupling of phenylpropanoids. Biological activity of these phenolic compounds ranges from antioxidant, antitumor (terminaloside P, IC50 = 10 nM), anti-inflammatory, anti-neurodegenerative (schibitubin B, IC50 = 3.2 nM) and antiviral (patentiflorin A, IC50 = 14-23 nM) to antimicrobial. In addition, it was observed that several members of this group, namely enterolactone and its biochemical precursors also known as phytoestrogens, possess important protective properties. Most of these lignans and neolignans are presented in reasonable amounts in one's diet and thus the protection they provide against the colon and breast cancer, to name a few, is even more important to note. Similarly, neuroprotective properties were observed (schisanwilsonin G, IC50 = 3.2 nM) These structural motives also serve as an important starting point in the development of anticancer drugs. Presumably the most famous members of this family, etoposide and teniposide, synthetic derivatives of podophyllotoxin, are used in the clinical treatment of lymphocytic leukemia, certain brain tumors, and lung tumors already for nearly 20 years. This review describes 413 lignans and neolignans which have been isolated between 2016 and mid-2018 being reported in more than 300 peer-reviewed articles. It covers their source, structure elucidation, and bioactivity. Within the review, the structure-based overview of compounds as well as the bioactivity-based overview of compounds are described.
- MeSH
- lidé MeSH
- lignany chemie farmakologie MeSH
- rostliny metabolismus MeSH
- sekundární metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
A very short three-step approach to trans,trans,trans-2,5-diaryl-3,4-dimethyltetrahydrofuran lignans is reported. The carbon skeleton is assembled in a single step based on an unprecedented tandem reaction consisting of 1,2-addition of aryllithium reagents to α,β-unsaturated aldehydes, ruthenium-catalyzed redox isomerization of the resulting alkoxides to enolates and their dimerization triggered by single electron oxidation. The resulting 2,3-dialkyl-1,4-diketones form with moderate to good d/l-diastereoselectivity and are transformed to the target tetrahydrofuran lignans by reduction and diastereoselective cycloetherification.
- MeSH
- aldehydy chemická syntéza chemie MeSH
- biomimetika MeSH
- cyklizace MeSH
- furany chemická syntéza chemie MeSH
- isomerie MeSH
- katalýza MeSH
- krystalografie rentgenová MeSH
- lignany chemická syntéza chemie MeSH
- molekulární modely MeSH
- oxidace-redukce MeSH
- oxidační párování MeSH
- ruthenium chemie MeSH
- techniky syntetické chemie MeSH
- Publikační typ
- časopisecké články MeSH
Warfarin is a commonly used anticoagulant drug and is a derivate of coumarin. Cytochrome P450 2C9 (CYP2C9) plays the key role in transformation of coumarin and thus, influences determination of warfarin dosage. A number of factors including dietary compounds such as sesamin, caffeic acid and ferulic acids can regulate the activity of CYP2C9. The present study tested the hypothesis that sesamin, episesamin, caffeic acid and ferulic acid decreases the rate of warfarin 7-hydroxylation via inhibition of hepatic CYP2C9. The experiments were conducted on hepatic microsomes from human donors. It was demonstrated that the rate of 7-hydroxylation of warfarin was significantly decreased in the presence of sesamin in the range of concentrations from 5 to 500 nM, and was not affected by episesamin, caffeic acid and ferulic acid in the same range of concentrations. The kinetic analysis indicated non-competitive type of inhibition by sesamin with Ki = 202 ± 18 nM. In conclusion, the results of our in vitro study revealed that sesamin was able to inhibit formation of a major metabolite of warfarin, 7-hydroxywarfarin. The potentially negative consequences of the consumption of high amounts of sesamin-containing food or dietary supplements in warfarin-treated patients need to be further studied.
- MeSH
- antikoagulancia metabolismus MeSH
- dioxoly chemie farmakologie MeSH
- hydroxylace MeSH
- inhibiční koncentrace 50 MeSH
- jaterní mikrozomy metabolismus MeSH
- kinetika MeSH
- kyseliny kávové farmakologie MeSH
- kyseliny kumarové farmakologie MeSH
- lidé MeSH
- lignany chemie farmakologie MeSH
- potraviny MeSH
- potravní doplňky MeSH
- warfarin metabolismus MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The nuclear receptors peroxisome proliferator-activated receptor γ (PPARγ) and its hetero-dimerization partner retinoid X receptor α (RXRα) are considered as drug targets in the treatment of diseases like the metabolic syndrome and diabetes mellitus type 2. Effort has been made to develop new agonists for PPARγ to obtain ligands with more favorable properties than currently used drugs. Magnolol was previously described as dual agonist of PPARγ and RXRα. Here we show the structure-based rational design of a linked magnolol dimer within the ligand binding domain of PPARγ and its synthesis. Furthermore, we evaluated its binding properties and functionality as a PPARγ agonist in vitro with the purified PPARγ ligand binding domain (LBD) and in a cell-based nuclear receptor transactivation model in HEK293 cells. We determined the synthesized magnolol dimer to bind with much higher affinity to the purified PPARγ ligand binding domain than magnolol (K i values of 5.03 and 64.42 nM, respectively). Regarding their potency to transactivate a PPARγ-dependent luciferase gene both compounds were equally effective. This is likely due to the PPARγ specificity of the newly designed magnolol dimer and lack of RXRα-driven transactivation activity by this dimeric compound.
- MeSH
- bifenylové sloučeniny chemická syntéza chemie farmakologie MeSH
- dimerizace * MeSH
- HEK293 buňky MeSH
- lidé MeSH
- ligandy MeSH
- lignany chemická syntéza chemie farmakologie MeSH
- pioglitazon farmakologie MeSH
- PPAR gama agonisté chemie metabolismus MeSH
- proteinové domény MeSH
- racionální návrh léčiv * MeSH
- retinoidní X receptor alfa metabolismus MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- fytoestrogeny MeSH
- fyziologie výživy * MeSH
- lidé MeSH
- lignany * chemie metabolismus terapeutické užití MeSH
- rostliny MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Leoligin is a natural lignan found in Edelweiss (Leontopodium nivale ssp. alpinum). The aim of this study was to examine its influence on cholesterol efflux and to address the underlying mechanism of action. Leoligin increases apo A1- as well as 1% human plasma-mediated cholesterol efflux in THP-1 macrophages without affecting cell viability as determined by resazurin conversion. Western blot analysis revealed that the protein levels of the cholesterol efflux transporters ABCA1 and ABCG1 were upregulated, whereas the SR-B1 protein level remained unchanged upon treatment with leoligin (10 μM, 24 h). Quantitative reverse transcription PCR further uncovered that leoligin also increased ABCA1 and ABCG1 mRNA levels without affecting the half-life of the two mRNAs in the presence of actinomycin D, a transcription inhibitor. Proteome analysis revealed the modulation of protein expression fingerprint in the presence of leoligin. Taken together, these results suggest that leoligin induces cholesterol efflux in THP-1-derived macrophages by upregulating ABCA1 and ABCG1 expression. This novel activity suggests leoligin as a promising candidate for further studies addressing a possible preventive or therapeutic application in the context of atherosclerosis.
- MeSH
- ABC transportéry metabolismus MeSH
- Asteraceae chemie MeSH
- ateroskleróza MeSH
- biologický transport MeSH
- daktinomycin farmakologie MeSH
- lidé MeSH
- lignany chemie izolace a purifikace farmakologie MeSH
- makrofágy metabolismus MeSH
- messenger RNA metabolismus MeSH
- molekulární struktura MeSH
- oxaziny metabolismus MeSH
- polymerázová řetězová reakce MeSH
- sirotčí receptory metabolismus MeSH
- western blotting MeSH
- xantheny metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The aim of the present study was to determine the structural requirements for dibenzocyclooctadiene lignans essential for P-glycoprotein inhibition. Altogether 15 structurally related lignans isolated from Schisandra chinensis or prepared by modification of their backbone were investigated, including three pairs of enantiomers. P-Glycoprotein inhibition was quantified using a doxorubicin accumulation assay in human promyelotic leukemia HL60/MDR cells overexpressing P-glycoprotein. A preliminary quantitative structure-activity relationship analysis revealed three main structural features involved in P-glycoprotein inhibition: a 1,2,3-trimethoxy moiety, a 6-acyloxy group, and the absence of a 7-hydroxy group. The most effective inhibitors, (-)-gomisin N (1) and (+)-deoxyschizandrin [(+)-2], were selected for further evaluation of their effects. Both these lignans restored the cytotoxic effect of doxorubicin in HL60/MDR cells and when combined with a subtoxic concentration of this compound increased the proportion of G2/M cells significantly, which is a usual response to treatment with this anticancer drug.
- MeSH
- cyklooktany * chemie izolace a purifikace farmakologie MeSH
- doxorubicin farmakologie MeSH
- kontrolní body fáze G2 buněčného cyklu účinky léků MeSH
- kvantitativní vztahy mezi strukturou a aktivitou MeSH
- lidé MeSH
- lignany * chemie izolace a purifikace farmakologie MeSH
- molekulární struktura MeSH
- P-glykoproteiny antagonisté a inhibitory MeSH
- polycyklické sloučeniny * chemie izolace a purifikace farmakologie MeSH
- Schisandra chemie MeSH
- semena rostlinná chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Rusko MeSH
