Potentiating the Benefits of Melatonin through Chemical Functionalization: Possible Impact on Multifactorial Neurodegenerative Disorders.

Although melatonin is an astonishing molecule, it is possible that chemistry will help in the discovery of new compounds derived from it that may exceed our expectations regarding antioxidant protection and perhaps even neuroprotection. This review briefly summarizes the significant amount of data gathered to date regarding the multiple health benefits of melatonin and related compounds. This review also highlights some of the most recent directions in the discovery of multifunctional pharmaceuticals intended to act as one-molecule multiple-target drugs with potential use in multifactorial diseases, including neurodegenerative disorders. Herein, we discuss the beneficial activities of melatonin derivatives reported to date, in addition to computational strategies to rationally design new derivatives by functionalization of the melatonin molecular framework. It is hoped that this review will promote more investigations on the subject from both experimental and theoretical perspectives.

Comparison between UVA- and zero-valent iron-activated persulfate processes for degrading propylparaben.

Conventional wastewater treatments are not efficient in removing parabens, which may thus end up in surface waters, posing a threat to aquatic biota and human health. As an alternative treatment, persulfate (PS)-driven advanced oxidation technologies have gained growing attention for removing these pollutants. In this study, the degradation of propylparaben (PrP) by UVA- and zero-valent iron (ZVI)-activated persulfate was investigated. The effects of initial PS concentration ([PS]0) and irradiance or ZVI concentration were explored using the Doehlert experimental design. For the UVA-activated system, the specific PrP degradation rate (k) and percent removal were consistently higher for increasing [PS]0 and irradiance, varying in the ranges 0.0053-0.0192 min-1 and 37.9-77.3%, respectively. In contrast, extremely fast PrP degradation was achieved through the ZVI/PS process (0.3304 < k < 0.9212 min-1), with removal percentages above 97.5%; in this case, paraben degradation was hindered for a ZVI dosage beyond 40 mg L-1. Regarding toxicity, ECOSAR predictions suggest that the degradation products elucidated by LC-MS/MS are less toxic than PrP toward fish, daphnid, and green algae. In addition, both processes showed to be strongly dependent on the water matrix, being ZVI/PS more impacted for a MBR effluent, although its performance was much better than that exhibited by the UVA-driven process (t1/2 of 65.4 and 276.1 min, respectively).

Synthesis, Antioxidant Activity and Cytotoxicity of N-Functionalized Organotellurides.

The use of antioxidants is the most effective means to protect the organism against cellular damage caused by oxidative stress. In this context, organotellurides have been described as promising antioxidant agents for decades. Herein, a series of N-functionalized organotellurium compounds has been tested as antioxidant and presented remarkable activities by three different in vitro chemical assays. They were able to reduce DPPH radical with IC50 values ranging from 5.08 to 19.20 µg mL-1, and some of them also reduced ABTS+ radical and TPTZ-Fe3+ complex in ABTS+ and FRAP assays, respectively. Initial structure-activity relationship discloses that the nature of N-substituent strongly influenced both activity and cytotoxicity of the studied compounds. Furthermore, radical scavenging activities of N-functionalized organotellurides have been compared with those of their selenilated congeners, demonstrating that the presence of tellurium atom has an essential role in antioxidant activity.

New ß-orcinol depsides from Hypotrachyna caraccensis, a lichen from the páramo ecosystem and their free radical scavenging activity.

The new hypotrachynin A (1) and B (2) along with the known (+)-(9b-R)-usnic (3) and methylstictic acids (4) were isolated for the first time from Hypotrachyna caraccensis. Additionally, their potency and reactivity as DPPH• scavengers was determined by a kinetic study calculating their EC50 and second-order rate constants (k2). Considering 1-4 could be dermatological agents, their n-octanol-water partition coefficients and standard molar Gibbs free energies of transfer were calculated as estimation of their lipophilicity and skin penetration. Compounds 1, 3 and 4 were less potent than 2 (EC50 = 3.3014; 1.7540; 2.6652 vs 0.7376) as DPPH• scavengers, in turn 4, was the most reactive with a comparable k2 to the antioxidant BHT (k2 = (232 ± 24) × 10-2 vs (564 ± 12) × 10-2 M-1 s-1, respectively). Since 2 and 4 had an optimal lipophilicity and permeability for skin penetration, they might be developed as topical ingredients to prevent oxidative damage.

Actividad antioxidante del complejo de inclusión del extracto de semilla de Bixa orellana en ß-ciclodextrina obtenido por CO2 supercrítico / Antioxidant activity of the inclusion complex of Bixa orellana seeds extract in ß-cyclodextrin obtained by supercritical CO2

Antecedentes: los extractos de Bixa orellana son utilizados como colorante de alimentos, y presentan una actividad antioxidante de importancia farmacéutica. Su uso puede limitarse por su inestabilidad, donde el proceso de inclusión en ß-ciclodextrina (ß-CD) por fluido supercrítico con CO2 (FSC-CO2) es una alternativa para mediar esta desventaja. Objetivos: comparar diferentes condiciones de temperatura y presión de extracción por FSC-CO2, para determinar cuál de estas permite obtener un extracto de Bixa orellana con mayor actividad antioxidante, y evaluar el efecto de la inclusión en ß-CD, en dicha capacidad antioxidante. Métodos: se obtuvieron extractos por FSC-CO2 variando condiciones de presión y temperatura: (I) 3583 psi, 35°C, (II) 1413 psi, 35°C, (III) 2184 psi, 45°C, (IV) 5076 psi, 45°C, y (V) 2300 psi, 40°C. Se evaluó la actividad antioxidante de los extractos obtenidos mediante el método DPPH, determinando su IC50. Se realizó el complejo de inclusión en ß-CD del extracto que presentó la mayor actividad antioxidante, por el método FSC-CO2, y fue caracterizado por IR, DSC y RMN. Mediante análisis comparativo de los espectros de la ß-CD, extracto libre y el complejo extracto/ß-CD, se verificó el acomplejamiento, y se evaluó la capacidad antioxidante del complejo de inclusión. Resultados: el extracto con mayor actividad antioxidante se obtuvo bajo la condición de extracción IV, con un IC50 de 23,55 µg/ mL, seguido del extracto II (28,76 µg/mL), del extracto III (37,23 µg/mL), del extracto V (81,09 µg/mL) y del extracto I (193,82 µg/mL), los cuales presentaron diferencias significativas (P<0,01). Los espectros obtenidos por IR, DSC y RMN presentaron desplazamientos propios del proceso de encapsulamiento. El valor IC50 del complejo extracto/ß-CD fue de 104,84 µg/mL, siendo significativamente mayor al valor obtenido para el extracto puro (23,55 µg/mL). Conclusión: el extracto de Bixa orellana con una actividad antioxidante mayor se obtuvo por fluido supercrítico a 5076 psi de presión y 45°C de temperatura. Las variaciones de los espectros IR, DSC y RMN demuestran la inclusión del extracto en la ß-CD, y los valores de IC50 indican el efecto protector de la ß-CD ante la reacción con el radical DPPH.

Background: Bixa orellana extracts are used to food coloring and it is important in pharmaceutical industry as a potential source of antioxidant activity. The application may be limited because it is unstable, but the process of inclusion in ß-cyclodextrin (ß-CD) by supercritical fluid CO2 (FSC-CO2) is an alternative to mediate this disadvantage. Objectives: we compared different conditions of temperature and pressure of FSC-CO2 extraction, to obtain a Bixa orellana extract with excellent antioxidant activity, and we evaluated the effect of inclusion in ß-CD in the antioxidant capacity. Methods: extracts were obtained by FSC-CO2 with different conditions of pressure and temperature: (I) 3583 psi, 35°C, (II) 1413 psi, 35°C, (III) 2184 psi, 45°C, (IV) 5076 psi, 45°C, and (V) 2300 psi, 40°C. The antioxidant activity by DPPH assay was determined and the IC50 was evaluated. We performed the inclusion complex in ß-CD with the highest antioxidant activity extract. The extract/ß-CD complex was characterized by IR, DSC and NMR. This complexation was verified by comparative analysis of the spectra of the ß-CD, free extract and ß-CD/extract complex. The antioxidant capacity of this inclusion complex was evaluated. Results: the extract with highest antioxidant activity was obtained under the extraction condition IV, with an IC50 of 23.55 µg/mL, followed extract II (28.76 µg/mL), extract III (37.23 µg/mL), extract V (81.09 µg/mL) and extract I (193.82 µg/mL). Analysis showed significant differences (P<0.01) between these extracts. The spectra obtained by IR, DSC and NMR evidence the encapsulation process. The IC50 value of the extract/ß-CD complex (104.84 µg/mL) was significantly higher than the value obtained for the pure extract (23.55 µg/mL). Conclusions: the highest antioxidant activity of Bixa orellana extracts was obtained by supercritical fluid pressure at 5076 psi and temperature of 45°C. Variations in IR, DSC and NMR spectra showed the inclusion of the ß-CD/extract, and the IC50 values indicated the protective effect of ß-CD to the reaction with DPPH radical.

Synthesis and radical scavenger properties of novel spirochromenes derived from steroid sapogenins.

Tandem aldol condensation between steroid sapogenins and hydroxylated benzaldehydes afforded steroidal spirochromenes. Compounds that bear a phenolic hydroxyl group at position C-6', obtained by a reaction with 2,5-dihydroxybenzaldehyde, showed approximately 80% of maximal radical scavenging activity in the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay at 288 nM. In contrast, the starting steroid sapogenins and the spirochromenes without a phenolic group in the side chain proved to be inactive.

In vitro antioxidant capacity and free radical scavenging evaluation of active metabolite constituents of Newbouldia laevis ethanolic leaf extract

BACKGROUND: The aim of the present study was to evaluate the in vitro antioxidant and free radical scavenging capacity of bioactive metabolites present in Newbouldia laevis leaf extract. RESULTS: Chromatographic and spectrophotometric methods were used in the study and modified where necessary in the study. Bioactivity of the extract was determined at 10 µg/ml, 50 µg/ml, 100 µg/ml, 200 µg/ml and 400 µg/ml concentrations expressed in % inhibition. The yield of the ethanolic leaf extract of N.laevis was 30.3 g (9.93%). Evaluation of bioactive metabolic constituents gave high levels of ascorbic acid (515.53 ± 12 IU/100 g [25.7 mg/100 g]), vitamin E (26.46 ± 1.08 IU/100 g), saponins (6.2 ± 0.10), alkaloids (2.20 ± 0.03), cardiac glycosides(1.48 ± 0.22), amino acids and steroids (8.01 ± 0.04) measured in mg/100 g dry weight; moderate levels of vitamin A (188.28 ± 6.19 IU/100 g), tannins (0.09 ± 0.30), terpenoids (3.42 ± 0.67); low level of flavonoids (1.01 ± 0.34 mg/100 g) and absence of cyanogenic glycosides, carboxylic acids and aldehydes/ketones. The extracts percentage inhibition of DPPH, hydroxyl radical (OH.), superoxide anion (O2 .-), iron chelating, nitric oxide radical (NO), peroxynitrite (ONOO-), singlet oxygen (1O2), hypochlorous acid (HOCl), lipid peroxidation (LPO) and FRAP showed a concentration-dependent antioxidant activity with no significant difference with the controls. Though, IC50 of the extract showed significant difference only in singlet oxygen (1O2) and iron chelating activity when compared with the controls. CONCLUSIONS: The extract is a potential source of antioxidants/free radical scavengers having important metabolites which maybe linked to its ethno-medicinal use.

Biological evaluation of morin and its new oxovanadium(IV) complex as antioxidant and specific anti-cancer agents.

It is known that flavonoids possess, among others, antioxidant and antitumoral properties that depend on their molecular structure. The central objective if this study was to investigate the potential antioxidant and antiproliferative properties of the flavonol morin and its new oxovanadium(IV) complex (VOmor) that was synthesized in order to modify the morin chemical structure. Two osteoblast (UMR106 and MC3T3E1), two breast tumor (T47D and SKBR3) and breast epithelial cell lines in culture were used for the antitumoral determinations. Additionally, a comparative study of their antioxidant capacities using different radicals (DPPH, ABTS(+), OH, O2(-), ROO) was performed. Selected mechanisms of action were studied using the breast cancer cell lines. Results obtained show that morin and its complex behaved as good antioxidant agents for some of the radicals and that the complexation improved the behavior with respect to OH and O2(-) radicals being morin more effective as ROO scavenger. A considerable variation in sensitivity was observed in the breast cancer cells but non-specificity was found for the treatment of osteosarcoma. Moreover, the compounds did not affect the normal proliferation of the breast epithelial mammal cells. The mechanistic studies demonstrated that the complex did not generate reactive oxygen species in the cells (confirming the in vitro studies) and did not produce any damage of DNA. The plasmatic membrane was observed to be damaged only in the SKBR3 cell line. In contrast, the perturbation of the mitochondrial membrane potential and the activation of caspase 3/7 for the breast tumor cells revealed an apoptotic cell death process. All these results collectively suggested that VOmor complex could serve as promising pharmacologically active substance against breast cancer treatment.

Actividad antioxidante de clones de cacao (Theobroma cacao l. ) finos y aromáticos cultivados en el estado de Chiapas, México / Antioxidant activity of clones of cocoa (Theobroma cacao L.) fine and aromatic grown in the state of Chiapas-México

Objetivo: determinar la capacidad antioxidante y contenido de grasa de clones de cacao, provenientes de especies nativas del Estado de Chiapas, México. Materiales y métodos: en extractos de 34 muestras semillas de cacao diluidas en metanol al 95% y clasificadas según pH en tres grupos: I (5,52-5,90), II (5,91- 6,28) y III (6,29-6,67), se realizaron ensayos analíticos de variables físicas y químicas. Se evaluó la inhibición de radicales 2,2-difenil-2-picrilhidrazil (DPPH) a 517 nm, el contenido de polifenoles mediante el reactivo de folin-ciocalteu (FCR) a 765 nm y cantidad de grasas totales según método AOAC. Se aplicó un ANOVA al nivel del 95%, con post prueba Tukey para comparar de medias muestrales y determinar diferencias significativas (p<0.05), además de sus correlaciones lineales. Resultados: El Grupo I con menor pH, mostró menor contenido calórico (26,3±3,6% de grasas), posee la mejor actividad antioxidante con menor valor EC50 de 4182 ppm y mayor contenido de polifenoles 6,6±0,32 equivalentes de ácido gálico por 100 g de muestra seca. Conclusión: El cacao chiapaneco posee importantes ventajas competitivas en el mercado, por su calidad como alimento funcional-nutracéutico y como materia prima para la industria alimentaria, fuente de antioxidantes y aditivos naturales, con potencial consumo en la industria farmacéutica y cosmética internacional.

Objective: To determine antioxidant capacity and fat content of cacao clones from the State of Chiapas, Mexico. Materials and Methods: 34 cocoa beans samples were diluted in 95% methanol and classified by pH in: group I (5.52-5.90), group II (5.91- 6.28), and group III (6.29-6.67). Chemical and physical analysis were developed. 2,2- diphenyl-2-picrylhydrazyl (DPPH) inhibition was evaluated at 517 nm. Polyphenol and fat contents were evaluated by Folin-Ciocalteu Reagent at 765 nm and AOAC method, respectively. Differences in variables were evaluated by ANOVA and Tukey test, in addition to its linear correlations. Results: Group I showed the lowest caloric content (26.3±3.6% fat), the best antioxidant activity with lower EC50 value of 4182 ppm and the highest polyphenol content (6.6±0.3 gallic acid/100 g dry sample). Conclusion: Chiapas cocoa has significant competitive advantages due to its quality as a functional and nutraceutical food. It is a good raw material for food industry because it is a good source of antioxidants and natural additives. Furthermore, it is a potential ingredient in the international pharmaceutical and cosmetic industry.

Antioxidant activity of plant extracts from Colombian flora / Atividade antioxidante de extrato de plantas da flora colombiana

In this study the antioxidant activity of forty-six methanol plant extracts, from the botanical families Asteraceae, Euphorbiaceae, Melastomataceae, Rubiaceae and Solanaceae, collected at the Regional Natural Park Ucumarí (RNPU, Risaralda, Colombia), were established by using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging assay. The plant extracts that showed the greatest antioxidant activity were Phyllanthus sp. (54.0 percent, Euphorbiaceae), followed by the two species belonging to the Melastomataceae family Tibouchina grossa (47.0 percent) and Miconia lehmannii Cogn. (45.3 percent) and continuing with Lycianthes radiata (Sendt.) Bitter. (41.5 percent, Solanaceae). This is the first report on the antioxidant activity of these Colombian species.

Neste estudo a atividade antioxidante de quarenta e seis extratos metanólicos de plantas das famílias botânicas Asteraceae, Euphorbiaceae, Melastomataceae, Rubiaceae e Solanaceae, coletadas no Parque Regional Natural Ucumarí (PRNU, Risaralda, Colômbia), foi determinada usando o ensaio de captação de radical livre de 1,1 difenil-2-picrilhidrazil (DPPH). Os extratos das plantas que mostraram a maior atividade antioxidante foram Phyllanthus sp. (54.0 por cento, Euphorbiaceae), seguido por duas espécies da família de Melastomataceae Tibouchina grossa (47.0 por cento) e Miconia lehmannii Cogn. (45.3 por cento) e Lycianthes radiata (Sendt.) Bitter. (41.5 por cento, Solanaceae). Esta é a primeira informação da atividade antioxidante destas espécies.