Phytochemical Analysis and Antinociceptive Properties of Hydroalcoholic Extracts of Aleurites moluccanus Bark.

Aleurites moluccanus is used in folk medicine to treat many diseases including pain and inflammatory processes in general. Considering the potential of the leaf extract, evidenced in a previous study, the present study investigates the antinociceptive and anti-inflammatory properties of the hydroethanolic extract of A. moluccanus bark and isolated compounds in animal models of pain. The antinociceptive and anti-inflammatory activities of A. moluccanus bark were evaluated through hyperalgesia induced by carrageenan, PGE2, cytokines, bradykinin, epinephrine, Freund's complete adjuvant, and lipopolysaccharide. Five compounds were isolated from the dichloromethane bark extract: acetyl aleuritolic acid, atraric acid, spruceanol, (5ß,10α)-12-hydroxy-13-methoxy-8,11,13-podocarpatrien-3-one and sonderianol. To optimize the extraction conditions, ethanol 50, 70, and 90°GL were used as extracting solvent, in a 1 : 20 (w/v) drug : solvent ratio, under stirring at room temperature for 4 h. The extracts were named AMC50, AMC70, and AMC90, respectively. These extracts were administered to mice (250 mg/kg, p. o.) with reduced mechanical hyperalgesia activity in the carrageenan test. Of these, AMC90 showed the best results. Pure (5ß,10α)-12-hydroxy-13-methoxy-8,11,13-podocarpatrien-3-one showed a beneficial effect for up to 48 hours after the administration of carrageenan, while acetyl aleuritolic acid was effective only in the first hour. AMC90 was able to reverse the analgesia induced only by prostaglandin E2 and tumor necrosis factor. We also induced hyperalgesia using the lipopolysaccharide and Freund's complete adjuvant models, with positive results. These results support the antinociceptive and anti-inflammatory activity of A. moluccanus bark extract. The observed effects are partly due to the presence of acetyl aleuritolic acid, atraric acid, and (5ß,10α)-12-hydroxy-13-methoxy-8,11,13-podocarpatrien-3-one.

Methacrylate saccharide-based monomers for dental adhesive systems.

The aim of this in vitro study was to synthesize three new methacrylate monomers based on the modification of saccharides structures (glucose-Gluc, sucrose-Sucr and chitosan-Chit) with glycidyl methacrylate, and to use them in the composition of dental adhesives. Three methacrylate saccharide monomers were synthesized and characterized by mid-IR, 1H and 13C NMR, antioxidant activity and cytotoxic effect. Monomers included: one monosaccharide - Gluc-MA; one disaccharide - Sucr-MA; and one polysaccharide - Chit-MA. Primers containing HEMA, methacrylate saccharide monomers at concentrations of 0 (control), 1, 2 or 4 wt%, 60 wt% ethanol aqueous solution (pH3.0) and initiator system were formulated. Primers were used in conjunction with a bond step and composite paste to restore caries-free third molars, and dentin bond strength (24 hours and 6 month of storage in water), and antimicrobial activity (Alamar Blue test) were tested. Degree of conversion (DC) and maximum rate of polymerization (Rpmax) of the primers themselves were also analyzed. The mid-IR, 1H and 13C spectrum confirmed the presence of vinyl group on the structure of saccharides. Chit-MA showed low antioxidant activity and did not present a cytotoxic effect. Gluc-MA and Sucr-MA possess antioxidant and cytotoxic activity, concentration dependent. In the presence of methacrylate saccharide monomers, the primers showed DC comparable to the control group, except Gluc-MA4%, Sucr-MA4% and Chit-MA1%, which showed a range of 64.6 from 58.5 %DC. Rpmax was not statistically different for all the groups (p = 0.01). The bond strength of Sucr-MA1% increased from 25.7 (±2.8) to 40.6 (±5.3) MPa after 6 months of storage. All the synthesized monomers showed some antimicrobial activity after polymerization. Gluc-MA and Chit-MA 4% and Sucr-MA 1, 2 and 4% led to decrease bacterial metabolism. Sucr-MA 1% showed better results regarding the decrease in bacterial metabolism and increasing the bond strength after 6 months of storage.

Reaction of glycidyl methacrylate at the hydroxyl and carboxylic groups of poly(vinyl alcohol) and poly(acrylic acid): is this reaction mechanism still unclear?

Transesterification and epoxide ring-opening reactions are two mechanism routes that explain chemical modifications of macromolecules by glycidyl methacrylate (GMA). Although the coupling reaction of the GMA with macromolecules has widely been investigated, there are still mechanisms that remain to be explained when GMA is processed in an aqueous solution at different pH conditions. To this end, reaction mechanisms of poly(vinyl alcohol) (PVA) and poly(acrylic acid) (PAAc) by GMA in water in acidic and basic conditions were investigated thoroughly. The presence of hydroxyl groups in PVA and carboxyl groups in PAAc allowed for a better evaluation of the reaction mechanisms. The analysis of the (1)H and (13)C NMR spectra clearly demonstrated that the chemical reactions of GMA with carboxyl groups and alcohols of the macromolecules in an aqueous solution are dependent on pH conditions. At pH 3.5, the GMA reacts with both the carboxylic and the hydroxyl groups through an epoxide ring-opening mechanism. At pH 10.5, the GMA undergoes a hydrolysis process and reacts with hydroxyl groups by way of both the transesterification and the epoxide ring-opening mechanisms, whereas the ring-opening reaction is the preferential pathway.

A tetrahydro beta-carboline trisaccharide from Palicourea coriacea (Cham.) K. Schum.

A new tetrahydro beta-carboline alkaloid that has an oligosaccharide unit was isolated from the root extracts of the Palicourea coriacea. The structure was elucidated using spectral methods, including 2D NMR: COSY, HMQC, HMBC and NOESY.

Crispoic acid, a new compound from Laelia marginata (Orchidaceae), and biological evaluations against parasites, human cancer cell lines and Zika virus.

The phytochemical study of Laelia marginata (Lindl.) L. O. Williams (Orchidaceae) led to the isolation of a new natural product named crispoic acid (1), together with six other known compounds (2-7). The new natural product was identified as a dimer of eucomic acid and was structurally characterised based upon 1D and 2D NMR and HRMS data. Biological assays with plant crude extract, fractions and isolated compounds were performed against two human cancer cell lines (Hela and Siha), and the tropical parasites Trypanosoma cruzi and Leishmania (Leishmania) amazonensis. The phenantrenoid 9,10-dihydro-4-methoxyphenanthren-2,7-diol 2 was active against Hela and Siha cells (CC50 5.86 ± 0.19 and 20.78 ± 2.72 µg/mL, respectively). Sub-lethal concentrations of the flavone rhamnazin 4 were not able to rescue the viability of the Vero cells infected by Zika virus.

Synthesis and characterization of pectin derivative with antitumor property against Caco-2 colon cancer cells.

New pectin derivative (Pec-MA) was obtained in specific reaction conditions. The presence of maleoyl groups in Pec-MA structure was confirmed by (1)H NMR and FTIR spectroscopy. The substitution degree of Pec-MA (DS=24%) was determined by (1)H NMR. The properties of Pec-MA were investigated through WAXS, TGA/DTG, SEM and zeta potential techniques. The Pec-MA presented amorphous characteristics and higher-thermal stability compared to raw pectin (Pec). In addition, considerable morphological differences between Pec-MA and Pec were observed by SEM. The cytotoxic effect on the Caco-2 cells showed that the Pec-MA significantly inhibited the growth of colon cancer cells whereas the Pec-MA does not show any cytotoxic effect on the VERO healthy cells. This result opens new perspectives for the manufacture of biomaterials based on Pec with anti-tumor properties.

A urethane-based multimethacrylate mixture and its use in dental composites with combined high-performance properties.

OBJECTIVES: To synthesize and characterize different molar weight urethane multimethacrylates with a single stage (one-pot) procedure. To prepare and characterize the properties of related composites. METHODS: Two methacrylate precursors were initially synthesized. Then, these precursors and the multimethacrylate system formed by their coupling were characterized by FTIR and (1)H NMR. The final product was used as a matrix (with TEGDMA and SiO2 silanized microparticles) in the preparation of composites and their physical and mechanical properties were compared to those of a bis-GMA-based resin. Water sorption and solubility measurements of the composites were also performed. RESULTS: FTIR and NMR suggested that the proposed synthesis route yields a mixture of mainly urethane-di, -tri, and tetramethacrylates. The composites presented low polymerization shrinkage (e.g. 1.88±0.08% for a resin with 70% of SiO2) and high flexural strength (e.g. 124.74±9.68 MPa for a resin with 65% of SiO2) when compared to the bis-GMA based resin and other composites found to date. Water sorption and solubility results show that the composites were deemed compliant with ISO 4049 requirements. SIGNIFICANCE: The mixture containing different molar weight of urethane multimethacrylates showed to be an excellent substitute for bis-GMA, achieving an equilibrium of properties (unlike reports elsewhere which show the enhancement of some parameters in detriment to others) and composites with low polymerization shrinkage, suitable microhardness and degree of conversion, and up to standard water sorption/solubility and flexural strength.

Chemical constituents of Machaerium hirtum Vell. (Fabaceae) leaves and branches and its anti-inflammatory activity evaluation.

Leaves and branches of Machaerium hirtum Vell. (Fabaceae), native to South America, were subjected to phytopharmacological investigation in order to identify its major chemical constituents and evaluate its extracts, fractions and isolated compounds in assays for anti-inflammatory activities. These were performed using mouse ear edema model, pleurisy and myeloperoxidase activity assays. Six compounds were isolated and identified as the flavanones swertisin and isovitexin, the alkaloid 4-hydroxy-N-methylproline, the triterpenes friedelin and lupeol, and the steroids sitosterol and stigmasterol. These compounds were identified by nuclear magnetic resonance of (1)H and (13)C data, in comparison with literature.