28 research outputs found
Inhibitory activity of stilbenes against filamentous fungi
No full textStilbenoids (resveratrol and its derivatives) are secondary metabolites produced by plants as defence mechanism to microbial infection. These compounds are known for their anti-inflammatory action and health benefits in preventing a wide range of disorders (e.g. cancer and cardiovascular diseases). However, their antimicrobial properties are less investigated. A series of 8 stilbenoid compounds were synthesized and their antifungal activity against 19 wild strains of filamentous fungi and yeasts (isolated from the environment and food) was tested in vitro. Using an agar diffusion assay, compounds were tested at the concentration of 100 μg/ml on filamentous fungi and yeasts at 104 CFU/ml. The results showed that tested derivatives possess moderate antifungal activity: in particular, monomeric stilbenoids 3’-hydroxy-pterostilbene and piceatannol, and dimeric stilbenoids (±)-trans-δ-viniferin and pallidol were active against mycotoxigenic fungi
Polymeric stilbene derivatives in winemaking byproducts affect NF-kB mediated inflammatory response in Caco-2 cells
No full textResiduals from winemaking represents one of the most important byproducts in the Italian agri-food
scenario. Grape skins and stems reportedly contain high levels of various phenolics-based bioactives that - in
the family of stilbenoids - include resveratrol and the products ensuing from its radical-based polymerization.
Among these is the family of viniferins, that reportedly are able to interfere with the glucose metabolism in the
gut, by inhibiting extracellular or membrane enzymes involved in the final steps of starch breakdown and –
eventually - in glucose uptake[1, 2]. These same reports also highlighted the possibility that molecules in the
stilbenoids family could display some physiologically relevant synergism in their inhibitory activities[2].
Whereas resveratrol is known to interfere with a number of cellular processes, including suppression of
NF-B mediated responses, little is known about the ability of polymeric or modified stilbenoids in this regard.
Therefore, we took advantage of the introduction of a RT-qPCR-based assay for intracellular expression of
NF-B[3] to assess whether a number of naturally occurring and semi-synthetic resveratrol polymers (at
concentrations in the 5-25 M range) may affect intracellular expression of NF-B in response to the addition
of IL-1β, and to verify whether any effect of these species was synergistic with those observed for resveratrol
alone (at a fixed 5 M concentration).
In short, we observed concentration-dependent suppression of NF-B expression for all the tested
compounds but pterostilbene and pallidol (see structures here below). The inhibitory effect was in the order -
viniferin > L34 -viniferin > L23> resveratrol, where L34 (trimethoxy-resveratrol) and L23 (pterostilbene-transdihydrodimer)
represent a fully methylated analogue of resveratrol and a vastly methylated analogue of -
viniferin, respectively. However, L23 and L34 elicited only modest effects when added at 5-20 M to 5 M
resveratrol in synergistic studies. On the contrary, similar concentrations of the naturally occurring viniferins
significantly increased the effects of 5 M resveratrol, with -viniferin providing the largest suppressive effects,
evident already at viniferin concentrations as low as 5 M.
These data suggest that the bioactivities associated with resveratrol derivatives in wine and
winemaking byproducts are dictated by specific molecular features, and are not limited to the inhibition of
extracellular enzymes. Evidence is also provided as for possible co-operativity occurring – rather than
competition – among chemically related species. Further studies will verify whether these observations can be
of practical relevance, but these data circumstantially appear to support the “food better than pills” working
hypothesis as for outlining possible intervention strategies.
[1] Lavelli V., Harsha P. S. C. S., Ferranti P., Scarafoni A. & Iametti S. (2016) Grape skin phenolics as inhibitors
of mammalian alpha-glucosidase and alpha-amylase - effect of food matrix and processing on efficacy. Food
& Function 7, 1655-1663.
[2] Mattio L. M., Marengo M., Parravicini C., Eberini I., Dallavalle S., Bonomi F., Iametti S. & Pinto A. (2019)
Inhibition of pancreatic alpha-amylase by resveratrol derivatives: Biological activity and molecular modelling
evidence for cooperativity between viniferin enantiomers. Molecules 24, Art. Nr: 3225, DOI:
10.3390/molecules24183225
[3] Barbiroli, A., Capraro, J., Marulo, S., Gamba, M. & Scarafoni, A. (2019). Effects on the Caco-2 cells of a
hypoglycemic protein from lupin seeds in a solution and adsorbed on polystyrene nanoparticles to mimic a
complex food matrix. Biomolecules, 9(10), 606; https://doi.org/10.3390/biom910060
Synthesis of a leopolic acid-inspired tetramic acid with antimicrobial activity against multidrug-resistant bacteria
No full textThe increasing emergence of multidrug-resistant pathogens is one of the biggest threats to human health and food security. The discovery of new antibacterials, and in particular the finding of new scaffolds, is an imperative goal to stay ahead of the evolution of antibiotic resistance. Herein we report the synthesis of a 3-decyltetramic acid analogue of the ureido dipeptide natural antibiotic leopolic acid A. The key step in the synthetic strategy is an intramolecular Lacey-Dieckmann cyclization reaction of a linear precursor to obtain the desired 3-alkyl-substituted tetramic acid core. The synthesized analogue is more effective than the parent leopolic acid A against Gram-positive (Staphylococcus pseudintermedius) and Gram-negative (E. coli) bacteria (MIC 8 μg/mL and 64 μg/mL, respectively). Interestingly, the compound shows a significant activity against Staphylococcus pseudintermedius strains expressing a multidrug-resistant phenotype (average MIC 32 μg/mL on 30 strains tested). These results suggest that this molecule can be considered a promising starting point for the development of a novel class of antibacterial agents active also against resistant strains
Synthesis of a small collection of resveratrol-related stilbenoids and evaluation of their cytotoxic activity
No full textBackground: Within the huge class of plant secondary metabolites, resveratrol-derived stilbenoids present a wide structural diversity and mediate a great number of biological responses relevant for human health. In particular, resveratrol is known to modulate several pathways directly linked to cancer progression, as well as its analogue pterostilbene, characterized by increased metabolic stability and significant pharmacological activities.
Methods: In order to study the potential cytotoxicity of other natural stilbenoids, a small collection of simplified analogues has been synthesized and tested on melanoma A375, non-small cell lung cancer H460 and prostate PC3 tumor cell lines and human normal skin WS1 fibroblasts.
Conclusions: The structural determinants responsible for the activity have been highlighted, indicating that both lipophilicity and geometry of the most potent molecules might play a role on their antiproliferative activity. Moreover, to evaluate the ability of the selected molecules to produce DNA damage, the expression of the γ-H2AX after compound exposure was evaluated in WS1, H460 and A375 cell lines. Low levels of DNA damage were evidenced in normal WS1 fibroblasts exposed to 200 μM resveratrol, whereas in H460 and A375 lines the compound showed a significant damaging activity, confirming its selective behavior towards cancer cells. In the same way, stilbenoid analogues showing a conjugated benzofuran moiety revealed a very interesting profile compared to other already known derivatives. Further studies are still ongoing in order to identify more precise structure-activity relationships on resveratrol congeners
Structure-dependent biological activities of food-related stilbene derivatives isomers
No full textResveratrol, piceatannol and pterostilbene are stilbene derivatives in which two aromatic rings linked by an olefin bridge. Many stilbene derivatives have proven beneficial to human health, acting on risk factors for cancer, on cardiovascular and neurodegenerative diseases, on diabetes, and on osteoporosis.
All these monomeric polyphenols are particularly prone to oligomerization processes through oxidative coupling, originating complex structures such as dimers or oligomers that may be responsible for their beneficial effects. These natural oligomers present stereogenic centers, that could play a pivotal role in the interaction of this class of molecules with biological targets.
In this study, isomers of these compounds were synthesized, purified, and tested as for their ability to inhibit enzymes relevant to glucose metabolism (such as brush-border glucosidase and pancreatic alpha amylase), and to control inflammatory response in a suitable Caco-2 cell model. Results highlight the requirement for peculiar structural features as for eliciting individual effects, both in terms of the polymerization state of these phenolics and in terms of their three-dimensional structure
Grapevine stilbenoids as natural food preservatives : calorimetric and spectroscopic insights into the interaction with model cell membranes
No full textFood contamination with pathogenic microorganisms, such as Listeria monocytogenes, Salmonella enterica, Staphylococcus aureus and Bacillus cereus, is a common health concern. Natural products, which have been the main source of antimicrobials for centuries, may represent a turning point in alleviating the antibiotic crisis, and plant polyphenolic compounds are considered a promising source for new antibacterial agents. Resveratrol and resveratrol-derived monomers and oligomers (stilbenoids) have been shown to exert a variegated pattern of efficacy as antimicrobials depending on both the polyphenols' structure and the nature of the microorganisms, and the bacterial cell membrane seems to be one of their primary targets. In this scenario and based on the thermodynamic information reported in the literature about cell membranes, this study aimed at the investigation of the direct interaction of selected stilbenoids with a simple but informative model cell membrane. Three complete stilbenoid "monomer/dimer/dehydro-dimer" sets were chosen according to different geometries and substitution patterns. Micro-DSC was performed on 2 : 3 DPPC : DSPC small unilamellar vesicles with incorporated polyphenols at physiological pH and the results were integrated using complementary NMR data. The study highlighted the molecular determinants and mechanisms involved in the stilbenoid-membrane interaction, and the results were well correlated with the microbiological evidence previously assessed
Synthesis and Antimicrobial Activity of δ-Viniferin Analogues and Isosteres
No full textThe natural stilbenoid dehydro-δ-viniferin, containing a benzofuran core, has been recently identified as a promising antimicrobial agent. To define the structural elements relevant to its activity, we modified the styryl moiety, appended at C5 of the benzofuran ring. In this paper, we report the construction of stilbenoid-derived 2,3-diaryl-5-substituted benzofurans, which allowed us to prepare a focused collection of dehydro-δ-viniferin analogues. The antimicrobial activity of the synthesized compounds was evaluated against S. aureus ATCC29213. The simplified analogue 5,5′-(2-(4-hydroxyphenyl)benzofuran-3,5-diyl)bis(benzene-1,3-diol), obtained in three steps from 4-bromo-2-iodophenol (63% overall yield), emerged as a promising candidate for further investigation (MIC = 4 μg/mL)
Inhibition of Pancreatic α-amylase by Resveratrol Derivatives : Biological Activity and Molecular Modelling Evidence for Cooperativity between Viniferin Enantiomers
No full textTo improve the current understanding of the role of stilbenoids in the management of diabetes, the inhibition of the pancreatic α-amylase by resveratrol derivatives was investigated. To approach in a systematic way, the mechanistic and structural aspects of the interaction, potential bioactive agents were prepared as single molecules, that were used for the biological evaluation of the determinants of inhibitory binding. Some dimeric stilbenoids—in particular, viniferin isomers— were found to be better than the reference drug acarbose in inhibiting the pancreatic α-amylase. Racemic mixtures of viniferins were more effective inhibitors than the respective isolated pure enantiomers at an equivalent total concentration, and displayed cooperative effects not observed with the individual enantiomers. The molecular docking analysis provided a thermodynamics-based rationale for the measured inhibitory ability and for the observed synergistic effects. Indeed, the binding of additional ligands on the surface of the alpha-amylase was found to decrease the dissociation constant of inhibitors bound to the active site of the enzyme, thus providing a mechanistic rationale for the observed inhibitory synergies
Inhibition of pancreatic α-amylase by resveratrol-derived viniferins relates to their geometrical features and implies co-operative binding
No full textTo improve current understanding of the role of stilbenoids in the management of diabetes, the hypoglycaemic potential of resveratrol derivatives was investigated in terms of alpha-amylase inhibition. To tackle the mechanistic and structural issues of the interaction with the target protein, bioactive agents were prepared as single molecules, to be used for biological evaluation of the binding determinants. Some dimeric stilbenoids – trans-delta-viniferins, in particular – were found to be much better inhibitors of pancreatic α-amylase.than the reference drug, acarbose. Racemic mixtures of viniferins were more effective than the respective isolated pure enantiomers at equivalent total concentration. A markedly sigmoidal inhibition curve was observed for the (S, S) enantiomer of trans-delta-viniferin, with a Hill cooperativity coefficient (n ) close to 4 and a relatively high Kiapp (0.058 mM). In contrast, values of n were close to unity for the (R, R) enantiomer (n = 1.5; Kiapp = 0.043 mM) and for the high-affinity binding of an equimolar mixture of the (R, R) and (S, S) enantiomers (n = 1.2; Kiapp = 0.012 mM). Molecular docking analysis provided a thermodynamics-based rationale for the inhibitory ability of individual stilbenoids, for the cooperative behavior of viniferin enantiomers, and for the synergistic inhibition discussed above. Indeed, binding of additional ligands on the surface of alpha-amylase was found to decrease the dissociation constant of inhibitors bound to the active site of the enzyme. Finally, viniferins do not appear to compete with acarbose in the inhibition of pancreatic α-amylase. Rather, the evidence gathered so far points to a possible synergy among these classes of inhibitors, in spite of their remarkable structural differences. Studies are in progress to assess whether these synergistic effects could be relevant to developing therapeutic or preventive strategies for diabetes management
Sujeción narrativa y emociones familiares: A propósito de El silencio es un cuerpo que cae de Agustina Comedi
No full textThe interest in examining a documentary such as El silencio es un cuerpo que cae by Agustina Comedi (2017) is not limited to the analysis of the author\u27s biographical record of her father\u27s sexual past. It also allows for the mapping of past and present forms of homosexuality that may be unrecognizable in a present GLBT marked by greater public visibility and acceptability. In this sense, Comedi\u27s work is not only an “archive of feelings” (Cvetkovich, 2018) in which the emotional responses - personal and collective - that from the absence of familiar and public recognition built a gay culture at the end of the last century are exhibited. It is also an “affective map” (Flatley, 2008) that provides an experience of self-estrangement that defamiliarizes us from our own affective attachments and allows us to reorient the emotional grammar to which we are subject. In this archive of images that tells of a conjectural and fragmentary past —the secret homosexual drift of his father—, not only is a “heterobiography” composed (Boero, 2017). It also reveals in an opaque way the sentimental drift of a dissident body —his father\u27s, that of many other fags of that time— in the midst of the problematic fabric that makes up the family emotions.
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ARK: http://id.caicyt.gov.ar/ark:/s22504524/olchp9x7vEl interés por examinar una pieza documental como El silencio es un cuerpo que cae de Agustina Comedi (2017) no se limita al análisis del registro biográfico que la autora hace del pasado sexual de su padre. Permite también cartografiar formas pasadas y presentes de la homosexualidad que por su particularidad pueden resultar irreconocibles en un presente LGTB signado por una mayor visibilidad y aceptabilidad públicas. En tal sentido, el trabajo de Comedi no solo es un “archivo de sentimientos” (Cvetkovich, 2018) en el que se exhiben las respuestas afectivas —personales y colectivas— que desde la ausencia de reconocimiento familiar y público construyeron una cultura gay a fines del siglo pasado. Es también un “mapa afectivo” (Flatley, 2008) que proporciona una experiencia de auto-extrañamiento que nos desfamiliariza de los propios apegos afectivos y permite reorientar la gramática emocional a la que nos vemos sujetos. En ese archivo de imágenes que da cuenta de un pasado conjetural y fragmentario —la secreta deriva homosexual de su padre—, no solo se compone una “heterobiografía” (Boero, 2017). También se revela de modo opaco la deriva sentimental de un cuerpo disidente —el de su padre, el de muchas otras maricas de aquella época— en medio del tejido problemático que componen las emociones familiares.
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ARK: http://id.caicyt.gov.ar/ark:/s22504524/olchp9x7
