Synthesis and electrochemical and biological studies of novel coumarin-chalcone hybrid compounds.

A series of novel hydroxy-coumarin-chalcone hybrid compounds 2a-i has been synthesized by employing a simple and efficient methodology. An electrochemical characterization using cyclic voltammetry and ESR spectroscopy were carried out to characterize the oxidation mechanism for the target compounds. The antioxidant capacity and reactivity were determined by ORAC and ESR assays, respectively. Biological assays were assessed to evaluate the cytotoxicity and cytoprotection capacity against ROS/RNS on BAEC. The results revealed that all tested compounds present ORAC values that are much higher than other well-known antioxidant compounds such as quercetin and catechin. Compound 2e showed the highest ORAC value (14.1) and also presented a low oxidation potential, good scavenging capacity against hydroxyl radicals, low cytotoxicity, and high cytoprotective activity.

Use of pyrogallol red and pyranine as probes to evaluate antioxidant capacities towards hypochlorite.

Hypochlorite is a strong oxidant able to induce deleterious effects in biological systems. The goal of this work was to investigate the use of PGR and PYR as probes in assays aimed at evaluating antioxidant activities towards hypochorite and apply it to plant extracts employed in Chilean folk medicine. The consumption of PGR and PYR was evaluated from the decrease in the visible absorbance and fluorescence intensity, respectively. Total phenolic content was determined by the Folin Ciocalteau assay. PGR and PYR react with hypochlorite with different kinetics, being considerably faster the consumption of PGR. Different stoichiometric values were also determined: 0.7 molecules of PGR and 0.33 molecules of PYR were bleached per each molecule of added hypochlorite. Both probes were protected by antioxidants, but the rate of PGR bleaching was too fast to perform a kinetic analysis. For PYR, the protection took place without changes in its initial consumption rate, suggesting a competition between the dye and the antioxidant for hypochlorite. Plant extracts protected PYR giving a PYR-HOCl index that follows the order: Fuchsia magellanica ≈ Marrubium vulgare ≈ Tagetes minuta > Chenopodium ambrosoides ≈ Satureja montana > Thymus praecox. Based on both the kinetic data and the protection afforded by pure antioxidants, we selected PYR as the best probe. The proposed methodology allows evaluating an antioxidant capacity index of plant extracts related to the reactivity of the samples towards hypochlorite.

Host-guest interaction between new nitrooxoisoaporphine and ß-cyclodextrins: synthesis, electrochemical, electron spin resonance and molecular modeling studies.

A new nitrooxoisoaporphine derivative was synthetized and characterized by cyclic voltammetry and electron spin resonance. Its aqueous solubility was improved by complexes formation with ß-cyclodextrin, heptakis(2,6-di-O-methyl)-ß-cyclodextrin and (2-hydroxypropyl)-ß-cyclodextrin. In order to assess the inclusion degree reached by nitrooxoisoaporphine in cyclodextris cavity, the stability constants of formation of the complexes were determined by phase-solubility measurements obtaining in all cases a type-A(L) diagram. Moreover, electrochemical studies were carried out, where the observed change in the EPC value indicated a lower feasibility of the nitro group reduction. Additionally, a detailed spatial configuration is proposed for inclusion of derivate within the cyclodextrins cavity by 2D NMR techniques. Finally, these results are further interpreted by means of molecular modeling studies. Thus, theoretical results are in complete agreement with the experimental data.

Antitrypanosomal and antioxidant properties of 4-hydroxycoumarins derivatives.

In the present communication we prepared a series of six 4-hydroxycoumarin derivatives, isosters of quercetin, recognized as an antioxidant natural compound, with the aim of evaluating the antitrypanosomal activity against Trypanosoma cruzi, the parasite responsible for Chagas disease, and the antioxidant properties. We have used the 4-hydroxycoumarin moiety (compound 1) as the molecular template for the synthesis of compounds 2-7. These derivates have shown moderate trypanocidal activity. However they have been proved to be good antioxidants. In particular compound 7 is the most active antioxidant and it is, therefore, a potential candidate for a successful employment in conditions characterized by free radicals overproduction.

Molecular encapsulation of 5-nitroindazole derivatives in 2,6-dimethyl-beta-cyclodextrin: electrochemical and spectroscopic studies.

Four different 5-nitroindazole derivatives (1-4) and its inclusion with Heptakis(2,6-di-O-methyl)-beta-cyclodextrin (DMbetaCD) were investigated. The stoichiometric ratios and stability constants describing the extent of formation of the complexes were determined by phase-solubility measurements obtaining in all cases a type-A(L) diagram. Also electrochemical studies were carried out, where the observed change in the E(PC) value indicated a lower feasibility of the nitro group reduction. The same behavior was observed in the ESR studies. The detailed spatial configuration is proposed based on 2D NMR methods. These results are further interpreted using molecular modeling studies. The latter results are in good agreement with the experimental data.

Complexation of morin with three kinds of cyclodextrin. A thermodynamic and reactivity study.

Properties of inclusion complexes between morin (M) and beta-cyclodextrin (betaCD), 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD) and Heptakis (2,6-O-di methyl) beta-cyclodextrin (DMbetaCD) such as aqueous solubility and the association constants of this complex have been determined. The water solubility of morin was increased by inclusion with cyclodextrins. The phase-solubility diagrams drawn from UV spectral measurements are of the A(L)-type. Also ORAC(FL) studies were done. An increase in the antioxidant reactivity is observed when morin form inclusion complex with the three cyclodextrin studied. Finally, thermodynamics studies of cyclodextrin complexes indicated that for DMbetaCD the inclusion is primarily enthalpy-driven process meanwhile betaCD and HPbetaCD are entropy-driven processes. This is corroborated by the different inclusion geometries obtained by 2D-NMR.