Structural Design, Synthesis and Antioxidant, Antileishmania, Anti-Inflammatory and Anticancer Activities of a Novel Quercetin Acetylated Derivative.

Quercetin (Q) is a bioflavonoid with biological potential; however, poor solubility in water, extensive enzymatic metabolism and a reduced bioavailability limit its biopharmacological use. The aim of this study was to perform structural modification in Q by acetylation, thus, obtaining the quercetin pentaacetate (Q5) analogue, in order to investigate the biological potentials (antioxidant, antileishmania, anti-inflammatory and cytotoxicity activities) in cell cultures. Q5 was characterized by FTIR, 1H and 13C NMR spectra. The antioxidant potential was evaluated against the radical ABTS•+. The anti-inflammatory potential was evaluated by measuring the pro-inflammatory cytokine tumor necrosis factor (TNF) and the production of nitric oxide (NO) in peritoneal macrophages from BALB/c mice. Cytotoxicity tests were performed using the AlamarBlue method in cancer cells HepG2 (human hepatocarcinoma), HL-60 (promyelocytic leukemia) and MCR-5 (healthy human lung fibroblasts) as well as the MTT method for C6 cell cultures (rat glioma). Q and Q5 showed antioxidant activity of 29% and 18%, respectively, which is justified by the replacement of hydroxyls by acetyl groups. Q and Q5 showed concentration-dependent reductions in NO and TNF production (p < 0.05); Q and Q5 showed higher activity at concentrations > 40µM when compared to dexamethasone (20 µM). For the HL-60 lineage, Q5 demonstrated selectivity, inducing death in cancer cells, when compared to the healthy cell line MRC-5 (IC50 > 80 µM). Finally, the cytotoxic superiority of Q5 was verified (IC50 = 11 µM), which, at 50 µM for 24 h, induced changes in the morphology of C6 glioma cells characterized by a round body shape (not yet reported in the literature). The analogue Q5 had potential biological effects and may be promising for further investigations against other cell cultures, particularly neural ones.

Development and thermochemical characterization of an antioxidant material based on polyhydroxybutyrate electrospun microfibers.

The use of antioxidants such as curcumin (Cur) or quercetin (Que) in biomedical and biotechnological applications has been studied owing to their capability to prevent oxidative stress and inhibit free radicals. Using polyhydroxybutyrate (PHB) electrospun fibers is presented as a proper option to encapsulate curcumin and quercetin due to its biocompatibility and biodegradability characteristics. Electrospun fibers were obtained dissolving commercial PHB in chloroform:N,N-dimethylformamide (DMF) (4:1) at 7% m/V, and adding two different concentrations of antioxidant (Cur, and Que) 1%m/m, and 7% m/m. These polymeric solutions were electrospun at different conditions and the obtained fibers were characterized by scanning electron microscopy (SEM), thermogravimetric (TGA) analysis, and Fourier transform infrared spectroscopy (FT-IR). The curcumin and quercetin releases into phosphate buffer saline (PBS) at pH 7.4 were obtained in vitro and measured by spectrophotometry. Antioxidant activities were measured by spectrophotometry in a microplate reader using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. Fibers obtained with different formulations presented a chemical composition in accordance with PHB according to FTIR spectra, the diameters fluctuate between 0.761 ± 0.123 and 1.803 ± 0.557 µm, with qualities over 0.95 according to their morphology, and the melting temperature resulted near 178 °C according to the bibliography. The crystallinity of fibers decreases while curcumin or quercetin concentration increases for the studied interval, indeed, quercetin showed a higher impact on the relative crystallinity of fibers. Antioxidant activity of active compounds is maintained after encapsulation in PHB electrospun fibers, and quercetin resulted in near four times antioxidant activity compared to curcumin according to DPPH analysis.

Xyloglucan-based hybrid nanocomposite with potential for biomedical applications.

Natural polymer-based hybrid nanocomposites have been proposed as one of the most promising tools for biomedical applications, including disease treatment and diagnosis procedures. Xyloglucan nanocapsules can simultaneously load magnetic iron oxide nanoparticles and bioactive for a specific tissue, reducing the processes of degradation and metabolic inactivation of molecules with biological activity. In this work, magnetic nanocapsules of xyloglucan loaded with hydrophilic sulfated quercetin (MNXQ_SO3) were successfully synthesized by inverse miniemulsion process through interfacial polymerization. The polymeric shell formation of nanocapsules was evidenced by Fourier Transform Infrared spectroscopy and Transmission Electron Microscopy. The ferrofluid (Fe3O4@PAAS) incorporated into the xyloglucan nanocapsules was synthesized by hydrothermal method, using polyacrylic acid sodium salt as coating. Dynamic Light Scattering technique confirmed the nanomeric dimensions (202.3 nm) and the good colloidal stability (-40.2 mV) of MNXQ_SO3. The saturation magnetization analyses pointed out the superparamagnetic behavior of Fe3O4@PAAS (48 emu/g) and MNXQ_SO3 (4.2 emu/g). MNXQ_SO3 was able to modify the release profile of sulfated quercetin (67%) when compared to the free bioactive (100%), exhibiting a release profile compatible with the zero-order kinetic model. The results showed that the development of MNXQ_SO3 presents a new perspective for biomedical applications, including studies of targeted drug delivery.

Synthesis and spectral investigation of Al(III) catechin/beta-cyclodextrin and Al(III) quercetin/beta-cyclodextrin inclusion compounds.

Al-catechin/beta-cyclodextrin and Al-quercetin/beta-cyclodextrin (beta-CD) inclusion compounds were synthesized and characterized by IR, UV-vis, 1H and 13C NMR and TG and DTA analyses. Because quercetin is sparingly soluble in water, the stability constants of the Al-quercetin/beta-CD and Al-catechin/beta-CD compounds were determined by phase solubility studies. The AL-type diagrams indicated the formation of 1:1 inclusion compounds and allowed calculation of the stability constants. The thermodynamic parameters were obtained from the dependence of the stability constants on temperature and results indicated that the formation of the inclusion compounds is an enthalpically driven process. The thermal decomposition of the solid Al-quercetin/beta-CD and Al-catechin/beta-CD inclusion compounds took place at different stages, compared with the respective precursors, proving that an inclusion complexation process really occurred.