Search

Chalcones are bioactive molecules of natural and synthetic sources, whose physicochemical properties, reactivity, and biological activities are well-known among the scientific community. However, there are many molecules strictly related to chalcones with significantly less recognition like bis -chalcones. Several studies indicated that bis -chalcones have advantages over chalcones in specific bioactivities like anti-inflammatory activity. This review article describes the chemical structure and chemical properties of bis -chalcones, as well as the methods reported in the literature for the synthesis of these compounds highlighting the most recent developments. Finally, the anti-inflammatory activity of bis -chalcones is described, emphasizing the active structures found in literature and their mechanisms of action. [Display omitted] • Bis -chalcones are a subclass of chalcones that earned considerable interest. • Chemical synthesis of bis -chalcones based on established knowledge on chalcones. • Improvement of classic synthetic methodologies with new reaction conditions. • Very few bis- chalcones are associated with anti-inflammatory activity. • More studies on anti-inflammatory bis -chalcones are required to establish a SAR. [ABSTRACT FROM AUTHOR]

Abstract: It is shown that the relationship between the alkyl chain length of 3-alkyl-3′,4′,5,7 tetrahydroxyflavones (FnH) bearing alkyl chains of n =1, 4, 6, 10 carbons and their capacity to counter oxidative damage varies markedly with the nature of the biological system. In Cu2+-induced lipid peroxidation of low-density lipoprotein (LDL), the less hydrophobic short-chain F1H and F4H are probably located in the outer layer of LDL and parallel the reference flavonoid antioxidant, quercetin (Q) as effective inhibitors of lipid peroxidation. A marked inhibition of haemolysis induced in red blood cells (RBC) suspensions by the membrane-permeant oxidant, tert-butylhydroperoxide (t-BuOOH), is observed with F4H and F6H present at concentration in the micromolar range. However, F10H the most hydrophobic FnH is even more effective than Q against both haemolysis and lipid peroxidation as measured by malondialdehyde (MDA) equivalents. In oxidation of RBC by H2O2, at least 50 times more F6H and F10H than by t-BuOOH are required to only partly inhibit haemolysis and MDA production. The F1H, F4H and Q are found rather inactive under these conditions. At concentrations in the micromolar range, a marked protection against the cytotoxic effects of the t-BuOOH-induced oxidative stress in human skin NCTC 2544 keratinocytes is also exhibited by the four FnH antioxidants and is comparable to that of Q. Thus, the four FnH species under study may be considered as potent antioxidants which manifest complementary anti-oxidative actions in biological systems of markedly different complexity. [Copyright &y& Elsevier]

Nine Tunisian Thymus capitatus (L.) Hoff. et Link. populations harvested in six bioclimatic zones extending from the sub humid (550 mm rainfall/year) to the lower arid (96.3 mm rainfall/year), and grown at altitudes ranging from 60 to 600 m were assessed for their phenolic composition. The identification of phenolic compounds was revealed by UHPLC-DAD-ESI/MS n . 11 phenolic compounds including three phenolic acids (rosmarinic acid, salvianolic acid A, salvianolic acid E), three flavanones (hesperidin, eriodictyol and naringenin), two C-glycoside isomers of the flavone apigenin, one flavanol gallocatechine, one flavanonol taxifolin and one phenolic monoterpen (carvacrol) were identified. Differences in phenolic composition among populations, in relationship with altitudes and/or annual rainfall were shown. Higher amounts of total phenols, total flavonoids, rosmarinic acid and carvacrol were detected in samples from the most arid zones (96.3–167 mm rainfall/year) in comparison with populations located in wet lands (450–660 mm rainfall/year). The altitude within or between contiguous climates is a main factor influencing phenol compounds content. The chemical variation among the populations should lead to the selection of plants with high potential in order to use them in health care and food industry. [ABSTRACT FROM AUTHOR]

Thymus x citriodorus is a Lamiaceae plant extensively cultivated in the Mediterranean region and used for centuries in culinary and in traditional medicine. The present work describes the detailed phenolic composition of T. x citriodorus for the first time, by means of HPLC–DAD, ESI–MS and MSn and nuclear magnetic resonance (NMR) analyses. The ethanolic extract of T. x citriodorus was analyzed by reversed phase HPLC. The method of analysis was also validated concerning its linearity, instrumental and method precision (for repeatability, immediate precision and intermediate precision) and accuracy (absolute recovery study). The technique was combined with electrospray mass spectrometry in order to identify the phenolic compounds and the structure of the main phenolics was also confirmed by NMR analysis. The in-house validated HPLC–DAD method showed good linearity for the tested reference compounds as well as satisfactory repeatability and immediate precision values, for both instrument and method. Furthermore, the satisfactory results of intermediate precision analysis and recovery assays indicated that the chromatographic method could be used to quantify the main phenolic compounds of T. x citriodorus with adequate precision and accuracy. The extract was rich in rosmarinic acid (10.4±0.6mg/g extract) that is a widespread phenolic acid in Thymus plants, but also in luteolin-7-O-α-glucuronide (12±2mg/g extract), that was herein reported in Thymus for the first time. Other novel compounds comprised one eriodictyol dihexoside with O-glycosidic linkages, two eriodictyol-O-monohexosides, one quercetagetin dimethyl ether-O-hexoside, one naringenin-O-hexoside and chrysoeriol-7-β-O-glucoside. Having in mind the health-promoting properties reported in literature for some of the main polyphenols found in T. x citriodorus, we suggest that this plant has a high potential for being used as a functional food. [ABSTRACT FROM AUTHOR]

Highlights • Most abundant lipophilic and phenolic compounds in olive leaves are highlighted. • UV-B radiation and heat differently modulate the lipophilic and phenolic content of olive leaves. • Flavonoids, secoiridoids and monoterpenes are highly responsive to heat and UV-B radiation. • Hydroxycinnamic acids, triterpenes, sterols and fatty acids are little affected by UV-B and heat. Abstract Olea europaea L. is the basis of the olive oil chain value. Olive by-products remain economically underexplored despite their richness in polyphenols and fatty acids. Heat waves and raised UV-B radiation episodes (that increasingly affect Mediterranean orchards) may influence these compounds. Herein we characterize the most relevant leaf lipophilic and phenolic compounds of an important Portuguese cultivar Cobrançosa, immediately and 30 days after exposure to high UV-B radiation or heat shock (HS). Plants were exposed to either UV-B (12 kJ m−2 d-1) or HS (40 °C for 2 h) for two consecutive days. Hydroxycinnamic acids, triterpenes, sterols and fatty acids are less influenced by UV-B and HS, while the amounts of flavonoids, secoiridoids and monoterpenes increased. In particular, after both treatments, quercetin-3- O -glucoside levels increased in leaves, and UV-B stimulated oleuropein levels. HS reduced the amounts of verbascoside, oleuropein and luteolin-7- O -glucoside, while UV-B only decrease apigenin-7- O -rutinoside levels. Thirty days after UV-B and HS relief, these compounds showed different profiles. Whereas UV-B recovering plants showed increased amounts of thymol-β- d -glucopyranoside, in HS recovering plants, the increase was more relevant for oleuropein, chrysoeriol-7- O -glucoside and luteolin-7- O -glucoside. Data evidence that Cobrançosa leaves are particularly rich in luteolin-7- O -glucoside, oleuropein, and oleic and palmitic acids, and that their levels may be stimulated by climate-change related conditions, contributing to the economical valorisation of leaves. [ABSTRACT FROM AUTHOR]

The classical non-transmembrane protein tyrosine phosphatase 1B (PTP1B) has emerged as a key negative regulator of insulin signaling pathways that leads to insulin resistance, turning this enzyme a promising therapeutic target in the management of type 2 diabetes mellitus (T2DM). In the present work, the in vitro inhibitory activity of a panel of structurally related flavonoids, for recombinant human PTP1B was studied and the type of inhibition of the most active compounds further evaluated. The majority of the studied flavonoids was tested in this work for the first time, including flavonoid C13 , which was the most potent inhibitor. It was observed that the ability to inhibit PTP1B depends on the nature, position and number of substituents in the flavonoid structure, as the presence of both 7- and 8-OBn groups in the A ring, together with the presence of both 3′ and 4′-OMe groups in the B ring and the 3-OH group in the C ring; these substituents increase the flavonoids' ability to inhibit PTP1B. In conclusion, some of the tested flavonoids seem to be promising PTP1B inhibitors and potential effective agents in the management of T2DM, by increasing insulin sensitivity. [ABSTRACT FROM AUTHOR]

Neutrophils are considered the central cells of acute inflammation. Flavonoids have been suggested as therapeutic agents to avoid damages induced by inflammatory processes. It is well known the reactivity of flavonoids with hypochlorous acid produced by neutrophils, to form stable mono and dichlorinated products. In this study, we synthesized novel chlorinated flavonoids and investigated their effect in neutrophils' oxidative burst and in its lifespan, in comparison with the parent non-chlorinated flavonoids. The obtained results demonstrate that chlorinated flavonoids were more efficient than their parent compounds in modulating neutrophils' oxidative burst in phorbol myristate acetate-activated neutrophils. Some of the tested flavonoids drive neutrophil apoptosis in a caspase 3-dependent fashion. The present data showed that 8-chloro-3′,4′,5,7-tetrahydroxyflavone ( 4a ) constitute an alternative anti-inflammatory therapy, due to the proven ability to suppress mechanisms engaged at the onset and progression of inflammation. [ABSTRACT FROM AUTHOR]

Abstract: The lipoxygenase (LOX) products have been identified as mediators of a series of inflammatory diseases, namely rheumatoid arthritis, inflammatory bowel disease, psoriasis, allergic rhinitis, atherosclerosis and certain types of cancer. Hence, LOX inhibitors are of interest for the modulation of these phenomena and resolution of the inflammatory processes. During LOX activity, peroxyl radical complexes are part of the reaction and may function as sources of free radicals. Thus antioxidants, such as flavonoids, capable of inhibiting lipid peroxidation and scavenging free radicals, may act as LOX inhibitors. The aim of this work was to assess the structure–activity relationship among a series of flavonoids concerning 5-LOX inhibition, through a systematic study of the inhibition of the formation of LTB4 in human neutrophils. The type of inhibition of the flavonoids was further studied using soybean LOX, type I, and Saturation Transfer Difference 1H NMR (STD-1H NMR) was used to characterize the binding epitopes of the compounds to LOX-1. The obtained results reinforce flavonoids as effective inhibitors of LTB4 production in human neutrophils. It was also possible to establish a structure/activity relationship for the inhibitory activity and the type of inhibition. [Copyright &y& Elsevier]

Abstract: New flavonoid–porphyrin conjugates were synthesized using the cross-coupling Buchwald–Hartwig amination for the coupling of flavonoid and porphyrin moieties. A unique di-substituted flavone–porphyrin conjugate was also synthesized under similar reaction conditions for the first time. All the conjugates were fully characterized by NMR spectroscopy. The photophysical properties namely fluorescence and singlet oxygen production were evaluated considering their use for photodynamic therapy applications. [Copyright &y& Elsevier]

Abstract: Inflammation is a normal response towards tissue injury, but may become deleterious to the organism if uncontrolled. The overproduction of reactive species during the inflammatory process may cause or magnify the damage at inflammatory sites. Flavonoids have been suggested as therapeutic agents to avoid such damage, as these compounds exhibit anti-inflammatory activity, through the modulation of oxidative stress and signalling pathways. Both effects may attenuate neutrophils' activities at inflammatory sites. In this study, we investigated the structure/activity relationship of a series of flavonoids on the oxidative burst of human neutrophils in vitro, as a measure of its anti-inflammatory potential. Neutrophils were stimulated with phorbol-12-myristate-13-acetate, and fluorescence and chemiluminescence techniques were used to evaluate the generation of reactive oxygen species. All the tested flavonoids revealed the ability to modulate the neutrophil's oxidative burst. From the obtained results, the pivotal role of the catechol group in the B-ring was evidenced as well as the minor importance of the hydroxylations in the A-ring, which did not appear to be determinant for the activity, although clearly influencing the lipophilicity of the tested flavonoids. It is also clarified the importance of the methylation in the OH group at the B-ring catechol moiety. In conclusion, the obtained results uncover new possible strategies for the resolution of inflammatory processes, using flavonoids to modulate neutrophil's oxidative burst. [Copyright &y& Elsevier]

Abstract: Fourteen baicalein and 3,7-dihydroxyflavone derivatives were synthesized and evaluated for their inhibitory activity against the in vitro growth of three human tumor cell lines. The synthetic approaches were based on the reaction with prenyl or geranyl bromide in alkaline medium, followed by cyclization of the respective monoprenylated derivative. Dihydropyranoflavonoids were also obtained by one-pot synthesis, using Montmorillonite K10 clay as catalyst combined with microwave irradiation. In vitro screening of the compounds for cell growth inhibitory activity revealed that the presence of one geranyl group was associated with a remarkable increase in the inhibitory activity. Moreover, for the 3,7-dihydroxyflavone derivatives a marked increase in growth inhibitory effect was also observed for compounds with furan and pyran fused rings. The most active compounds were also studied regarding their effect on cell cycle profile and induction of apoptosis. Overall the results point to the relevant role of the prenylation of flavone scaffold in the growth inhibitory activity of cancer cells. [Copyright &y& Elsevier]

Abstract: A flavanol–anthocyanin condensed pigment was isolated from a commercial anthocyanin-rich purple corn powder and its structure elucidated by mass spectrometry and 1H and 13C NMR using 1D and 2D techniques (COSY, HSQC, HMBC). The compound was unequivocally identified as the dimer catechin-(4α→8)-cyanidin-3,5-O-diglucoside. In addition, six non-processed samples belonging to different corn varieties were analysed for their anthocyanin profiles, with the aim of checking if similar condensed pigments were present in native corn. The presence of condensed pigments was found in three corn varieties, whose identity was established from their UV and mass spectra and MS2 fragmentation patterns. The percentage of condensed pigments ranged between 0.3% and 3.2% of total anthocyanins. The whole of the observations made confirm that flavanol–anthocyanin condensed pigments can occur naturally in corn. [Copyright &y& Elsevier]

Abstract: 2-Styrylchromones (2-SC) are a chemical family of oxygen heterocyclic compounds, vinylogues of flavones (2-phenylchromones), whose occurrence in nature has been reported. Recently, several 2-SC derivatives were demonstrated to have antioxidant properties, namely, xanthine oxidase inhibition, hepatoprotection against pro-oxidant agents in cellular and non-cellular systems and scavenging activity against reactive oxygen and reactive nitrogen species (ROS and RNS). Considering these antioxidant properties, it may be hypothesised that the electrochemical redox behaviour of 2-SC contributes significantly to their activity. To test this hypothesis, the electrochemical behaviour of different 2-SC was studied, together with a number of flavonoids with well-known antioxidant activities, by cyclic voltammetry, and the results correlated to their ability to scavenge ROS and RNS. The results obtained showed that 2-SC with a catecholic B-ring have a low oxidation peak potential corresponding to the oxidation of the 3′,4′-OH (catechol) moiety. The compounds with a phenolic B-ring have a common peak, with oxidation potential values of about +0.4/+0.5V versus Ag/AgCl, corresponding to the oxidation of the 4′-OH. The oxidation of the hydroxyl substituents in the A-ring generated peaks of higher potentials (+0.7/+0.8V vs Ag/AgCl). The results from the scavenging assays were in agreement with those obtained from the cyclic voltammetry, that is, higher scavenging effects corresponded to lower values of oxidation potentials, with significant correlation coefficients. The values obtained for the studied flavonoids are in accordance with the literature, and reflect their relative antioxidant activity, when compared to the studied 2-SC. Thus, in this family of compounds, oxidation potentials obtained by cyclic voltammetry seem to be applicable as a general indicator of radical scavenging activity. [Copyright &y& Elsevier]

A condensation reaction between malvidin 3-glucoside (mv3gl) and catechin (cat) mediated by acetaldehyde and propionaldehyde was conducted in model solutions at two pH values (at 1.5 and 3.2). Acetaldehyde led to the formation of mv3gl-8-ethyl-8-cat (m/z at 809) widely reported in the literature, whereas propionaldehyde led to the formation of mv3gl-8-propyl-8-cat (m/z at 823) and its structural characterization is elucidated herein for the first time by 1D and 2D NMR. The formation of these alkyl-linked pigments is favoured at lower pH value as the alkyl linkage requires the formation of an aldehyde carbocation for a further condensation. [Copyright &y& Elsevier]

A range of fullerene–chalcone, fullerene–flavone, and fullerene–chromone dyads, including a bis(flavonyl)-fullerene dyad, were prepared by 1,3-dipolar cycloaddition reactions of azomethine ylides to C60 and by cyclopropanation of C60 with flavonyl malonates. Synthetic and natural flavonoid derivatives were used as starting materials. [Copyright &y& Elsevier]

• Cobrançosa olives are richer in organic acids, esters and carbohydrates. • C.Serpa olives present higher levels of phenolic compounds. • Stress modulates olives' phenolic/lipophilic contents in a cultivar-dependent way. • C.Serpa olives have higher stress susceptibility than Cobrançosa and C.C.Branco. • Olives can be enriched in bioactive compounds in response to environmental stresses. The awareness of the functional and nutraceutical properties of olives and olive oil bioactive constituents contributed to oliviculture recent increase. Olives' metabolism and nutritional quality are determined by how the olive-tree is coping to climate change-related episodes, which increasingly occur in the Mediterranean. We characterize the most relevant lipophilic and phenolic compounds of olives from Olea europaea cultivars [Cobrançosa, Cordovil de Castelo Branco and Cordovil de Serpa (C.Serpa)] exposed to drought + heat. Olives from the three cultivars presented a similar qualitative profile but differed in their relative richness. Cobrançosa olives are richer in organic acids, esters and carbohydrates, while C.Serpa olives have higher levels of phenolic compounds, particularly under control conditions. Drought + heat changed the quantitative profile of olives, in a way dependent on the cultivar, and C.Serpa olives showed the highest stress susceptibility. Climate change-related conditions stimulate the accumulation of relevant bioactive compounds in olives, contributing to increasing its nutritional value. [ABSTRACT FROM AUTHOR]