Synthesis, Photoisomerization, Antioxidant Activity, and Lipid-Lowering Effect of Ferulic Acid and Feruloyl Amides.

The Ugi four-component reaction employing naturally occurred ferulic acid (FA) is proposed as a convenient method to synthesize feruloyl tertiary amides. Applying this strategy, a peptoid-like derivative of ferulic acid (FEF77) containing 2 additional hydroxy-substituted aryl groups, has been synthesized. The influence of the configuration of the double bond of ferulic acid and feruloyl amide on the antioxidant activity has been investigated thanks to light-mediated isomerization studies. At the cellular level, both FA, trans and cis isomers of FEF77 were able to protect human endothelial cord vein (HECV) cells from the oxidative damage induced by exposure to hydrogen peroxide, as measured by cell viability and ROS production assays. Moreover, in steatotic FaO rat hepatoma cells, an in vitro model resembling non-alcoholic fatty liver disease (NAFLD), the molecules exhibited a lipid-lowering effect, which, along with the antioxidant properties, points to consider feruloyl amides for further investigations in a therapeutic perspective.

In vitro activity of natural phenolic compounds against fluconazole-resistant Candida species: a quantitative structure-activity relationship analysis.

AIMS: To evaluate the antifungal activity and to analyse the structure-activity relationship of eleven natural phenolic compounds against four Candida species which are resistant to fluconazole. METHODS AND RESULTS: Four different species of Candida isolates were used: Candida albicans, Candida krusei, Candida tropicalis and Candida dubliniensis. The phenolic compound carvacrol showed the highest anti-Candida bioactivity, followed by thymol and isoeugenol. The obtained minimum inhibitory concentration (MIC) values obtained were used in a quantitative structure-activity relationship (QSAR) analysis where the electronic, steric, thermodynamic and topological descriptors served as dependent variables. According to the descriptors obtained in this QSAR study, the antifungal activity of phenols has a first action specific character which is based on their interaction with plasma or mitochondrial membranes. The second action is based on a steric descriptor-the maximal and minimal projection of the area-which could explain the inability of some phenolic compounds to be biotransformed to quinones methylene by Candida species. CONCLUSIONS: According to the descriptors obtained in this QSAR study, the anti-Candida activity of ortho-substituted phenols is due to more than one action mechanism. The anti-Candida activity of phenolic compounds can be predicted by their molecular properties and structural characteristics. SIGNIFICANCE AND IMPACT OF THE STUDY: These results could be employed to predict the anti-Candida activity of new phenolic compounds in the search for new alternatives or complementary therapies to combat against candidiasis.

The effect of olive oil on osteoporosis prevention.

UNLABELLED: The incidence of osteoporosis and associated fractures is found to be lower in countries where the Mediterranean diet is predominant. These observations might be mediated by the active constituents of olive oil and especially phenolic compounds. OBJECTIVE: To review current knowledge by searching for all relevant publications since 2001 in the MEDLINE, EMBASE and Cochrane Library databases, using the descriptors: Mediterranean diet, virgin olive oil, phenols, bone, osteoblast and osteoporosis. RESULTS AND CONCLUSIONS: Published evidence suggests that olive oil phenols can be beneficial by preventing the loss of bone mass. It has been demonstrated that they can modulate the proliferative capacity and cell maturation of osteoblasts by increasing alkaline phosphatase activity and depositing calcium ions in the extracellular matrix. Further research on this issue is warranted, given the prevalence of osteoporosis and the few data available on the action of olive oil on bone.

Natural phenol-inspired porous polymers for efficient removal of tetracycline: Experimental and engineering analysis.

Efficient and feasible removal of trace antibiotics from wastewater is extremely important due to its environmental persistence, bioaccumulation, and toxicity, but still remains a huge challenge. Herein, three natural phenol-inspired porous organic polymers were fabricated from natural phenolic-derived monomers (p-hydroxy benzaldehyde, 2,4-dihydroxy benzaldehyde and 2,4,6-trihydroxy benzaldehyde) and melamine via polycondensation reaction. Characterization highlighted that the increasing contents of hydroxyl groups in monomers induced an increase of the polymer total porosity and promoted the formation of a highly microporous structure. With mesopore-dominated pore (average pore diameter 9.6 nm) and large pore volume (1.78 cm3/g), p-hydroxy benzaldehyde-based porous polymer (1-HBPP) exhibited ultra-high maximum adsorption capacity (qmax) of 697.6 mg/g for tetracycline (TC) antibiotic. Meanwhile, the porous networks and plentiful active sites of 1-HBPP enabled fast adsorption kinetics (within 10 min) for TC removal, which could be well described by the pseudo-second-order model. Dynamic adsorption studies showed that 1-HBPP could be used in fixed-bed adsorption column (FBAC) with high removal efficiency (breakthrough volume per unit mass, 13.2 L/g) and dynamic adsorption capacity (201.6 mg/g), which were much higher than other reported adsorbents. The breakthrough curves both well matched with Thomas and Yoon-Nelson models in FBAC treatment. Moreover, removal mechanism analysis affirmed that pore-filling, hydrogen bonding, electrostatic interactions and π-π stacking interactions were main driving forces for TC adsorption. The prepared natural phenol-inspired porous adsorbents show great potential in antibiotics removal from wastewater, and this strategy would promote the sustainable and high-value utilization of natural phenolic compounds.

Structural derivatization strategies of natural phenols by semi-synthesis and total-synthesis.

Structural derivatization of natural products has been a continuing and irreplaceable source of novel drug leads. Natural phenols are a broad category of natural products with wide pharmacological activity and have offered plenty of clinical drugs. However, the structural complexity and wide variety of natural phenols leads to the difficulty of structural derivatization. Skeleton analysis indicated most types of natural phenols can be structured by the combination and extension of three common fragments containing phenol, phenylpropanoid and benzoyl. Based on these fragments, the derivatization strategies of natural phenols were unified and comprehensively analyzed in this review. In addition to classical methods, advanced strategies with high selectivity, efficiency and practicality were emphasized. Total synthesis strategies of typical fragments such as stilbenes, chalcones and flavonoids were also covered and analyzed as the supplementary for supporting the diversity-oriented derivatization of natural phenols.

Semisynthetic Phenol Derivatives Obtained from Natural Phenols: Antimicrobial Activity and Molecular Properties.

Semisynthetic phenol derivatives were obtained from the natural phenols: thymol, carvacrol, eugenol, and guaiacol through catalytic oxychlorination, Williamson synthesis, and aromatic Claisen rearrangement. The compounds characterization was carried out by 1H NMR, 13C NMR, and mass spectrometry. The natural phenols and their semisynthetic derivatives were tested for their antimicrobial activity against the bacteria: Staphylococcus aureus, Escherichia coli, Listeria innocua, Pseudomonas aeruginosa, Salmonella enterica Typhimurium, Salmonella enterica ssp. enterica, and Bacillus cereus. Minimum inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) values were determined using concentrations from 220 to 3.44 µg mL-1. Most of the tested compounds presented MIC values ≤220 µg mL-1 for all the bacteria used in the assays. The molecular properties of the compounds were computed with the PM6 method. Through principle components analysis, the natural phenols and their semisynthetic derivatives with higher antimicrobial potential were grouped.

Determination of natural phenols in olive fruits by chitosan assisted matrix solid-phase dispersion microextraction and ultrahigh performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry.

A simple, efficient and low-cost method based on matrix solid-phase dispersion (MSPD) microextraction and ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS) was developed for the determination of seven main natural phenols (gallic acid, hydroxytyrosol, methyl gallate, luteolin 7-O-ß-d-glucoside, rutin, ellagic acid and oleuropein) and other eleven compounds in olive fruits. The experimental conditions for the MSPD extraction, including the type of adsorbent, the amount of dispersing sorbent, the grinding time, and the type of elution solvent were investigated and optimized. The optimized parameters were determined to be that middle-molecular-weight chitosan was used as adsorbent, the amount of middle-molecular-weight chitosan was selected to be 25mg, the grinding time was chosen to be 60s, and methanol: water (6:4, v:v) was used as elution solvent. Compared with reported methods, the proposed method was more simple, rapid, and efficient. Moreover, this method required less extraction time and less amount of sample and solvent. The method showed good linearity (r(2)≥0.9909) for the seven analytes, with the limits of detection in the range of 69.6-358.4ng/g. And recoveries were above 80.06%. The methodology was successfully applied to the extraction and determination of seven phenolic compounds in olive fruits（Canarii fructus）.

Enzymatic grafting of natural phenols to flax fibres: Development of antimicrobial properties.

Unbleached flax fibres for paper production were treated with laccase from Pycnoporus cinnabarinus and low molecular weight phenols (syringaldehyde - SA, acetosyringone - AS and p-coumaric acid - PCA) to evaluate the potential of this treatment to biomodify high cellulose content fibres. After the enzymatic treatment with the phenols, an increase in kappa number was found, probably due to a covalent binding of the phenoxy radicals on fibres. Grafting was more evident in pulps treated with PCA (an increase of 4 kappa number points with respect to the laccase control was achieved). Paper handsheets from treated pulps showed antimicrobial activity against the bacteria tested: Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella pneumoniae. An important reduction on microbial count was obtained after incubation of liquid cultures of the bacteria with grafted handsheets. AS and PCA grafted fibres showed a high antibacterial activity on K. pneumoniae, getting a nearly total growth inhibition. AS fibres also caused a high reduction in bacterial population of P. aeruginosa (97% reduction). Optical properties of handsheets from treated pulps were also determined, showing a brightness decrease and increase in coloration, evaluated by CIE L*a*b* system, caused by the laccase induced grafting of the phenols. The results suggest that these low molecular weight phenols, covalently bound to the flax fibres by the laccase treatment, can act as antimicrobial agents and produce handsheets with antimicrobial activity.

Discovery of Natural Phenols as G Protein-Coupled Receptor-35 (GPR35) Agonists.

We report the discovery and characterization of natural phenols as G protein-coupled receptor-35 (GPR35) agonists. Pharmacological characterization using label-free dynamic mass redistribution and Tango ß-arrestin translocation assays revealed that GPR35-active natural phenols are divergent in their biased agonism.