Luis Espinoza

Antifungal Activity of Eugenol Analogues. Influence of Different Substituents and Studies on Mechanism of Action

Twenty one phenylpropanoids (including eugenol and safrole) and synthetic analogues, thirteen of them new compounds, were evaluated for antifungal properties, first with non-targeted assays against a panel of human opportunistic pathogenic fungi. Some structure-activity relationships could be observed, mainly related to the influence of an allyl substituent at C-4, an OH group at C-1 and an OCH3 at C-2 or the presence of one or two NO2 groups in different positions of the benzene ring. All active compounds were tested in a second panel of clinical isolates of C. albicans and non-albicans Candida spp., Cryptococcus neoformans and dermatophytes. The eugenol derivative 4-allyl-2-methoxy-5-nitrophenol (2) was the most active structure against all strains tested, and therefore it was submitted to targeted assays. These studies showed that the antifungal activity of 2 was not reversed in the presence of an osmotic support such as sorbitol, suggesting that it does not act by inhibiting the fungal cell wall synthesis or assembly. On the other hand, the Ergosterol Assay showed that 2 did not bind to the main sterol of the fungal membrane up to 250 µg mL−1. In contrast, a 22% of fungal membrane damage was observed at concentrations = 1 × MIC and 71% at 4× MIC, when 2 was tested in the Cellular Leakage assay. The comparison of log P and MICs for all compounds revealed that the antifungal activity of the eugenol analogues would not to be related to lipophilicity.

ANTIOXIDANT CAPACITY OF EUGENOL DERIVATIVES

Toxicity and antioxidant capacity of eugenol derivatives (E2 = 2-Methoxy-4-[1-propenylphenyl]acetate, E3 = 4-Allyl-2-methoxyphenylacetate, E4 = 4-Allyl-2-methoxy-4-nitrophenol, E5 = 5-Allyl-3-nitrobenzene-1,2-diol, E6 = 4-Allyl-2-methoxy-5-nitrophenyl acetate) were evaluated in order to determine the influence of the sustituents. E2-E6 were synthesized from eugenol (E1). E1 was extracted from cloves oil, and E2-E6 were obtained through acetylation and nitration reactions. Antioxidant capacity evaluated by DPPH (1, 1-Diphenyl-2-picrylhydrazil) and ORAC fluorescein demonstrated that E1 and E5 have a higher capacity and the minor toxicity evaluated by red blood cells haemolysis and the Artemia saline test. In accordance with our results, the compounds (E1-E5) use in the pharmaceutical, cosmetic and or food industries could be suggested.

Synthesis and DPPH radical scavenging activity of prenylated phenol derivatives.

The synthesis of twenty six prenylated phenols derivatives is reported. These compounds were obtained under mild conditions via Electrophilic Aromatic Substitution (EAS) coupling reactions between phenol derivatives containing electron-donor subtituents and 3-methyl-2-buten-1-ol using BF3·OEt2. Dialkylations were also produced with this method. The formation of a chroman ring by intramolecular cyclization between a sp2 carbon from the prenyl group with the hydroxyl substituent in the ortho position occurred with some phenols. All the synthesized compounds were evaluated as antioxidants according to a DPPH radical scavenging activity assay. IC50 values of five synthesized compounds indicated they were as good antioxidants as Trolox™.

Effect of Polymer Micelles on Antifungal Activity of Geranylorcinol Compounds against Botrytis cinerea.

Herein, we explore the potential use of two micelle-forming block copolymers, i.e., Pluronic F-127 and poly(ethylene oxide)-b-poly(caprolactone), for application of fungicide agents. The polymer effect on the in vitro fungicide activity of a series of geranyl orcinol derivatives against Botrytis cinerea has been assessed. The results show that, for all test compounds, the incorporation into micelles, formed by Pluronic F-127, produces a great enhancement of the inhibitory effect on the growth of B. cinerea. For some compounds, at the lowest tested concentration (50 ppm), the percentage of inhibition increases significantly (from 0-10 to 80-90%) when the application is made using a polymer solution instead of an ethanol/water mixture. The synthesis and structural determination of a series of eight geranylphenols/diacetates, which were used as fungicide agents, are also discussed. These results suggest that polymer micelles are promising systems for application of crop-protecting agents.

Antifungal study of the resinous exudate and of meroterpenoids isolated from Psoralea glandulosa (Fabaceae)

ETHNOPHARMACOLOGICAL RELEVANCE Psoralea glandulosa L. (Fabaceae) is a medicinal resinous shrub used in Chilean folk medicine as antiseptic in treatment of infections and skin diseases caused by bacteria and fungus. AIM OF THE STUDY To evaluate the in vitro antifungal activity of the resin and the active components from P. glandulosa against clinical yeast isolates. MATERIALS AND METHODS Active compounds were obtained of the resinous exudate from aerial parts of P. glandulosa. Eight species of yeast were exposed to the resin and two major compounds. Minimum inhibitory concentration (MIC(80)) was determined according to the standard broth microdilution method. RESULTS Bakuchiol and 3-hydroxy-bakuchiol demonstrated potent activity with the MIC(80) ranging from 4 to >16 and 0.125 to 16 μg/mL, respectively. The resin had some degree of antifungal activity. CONCLUSIONS The overall results provided important information for the potential application of the 3-hydroxy-bakuchiol from P. glandulosa in the therapy of serious infection and skin diseases caused by clinical yeast.

Synthesis of geranylhydroquinone derivatives with potencial cytotoxic activity

Natural geranylhydroquinone 1 and geranyl-p-methoxyphenol 2 were prepared by Electrophilic Aromatic Substitution (EAS) reactions between geraniol and 1,4-hydroquinone or p-methoxyphenol respectively, using BF3∙Et2O as a catalyst. Furthermore, natural geranylquinone 3, geranyl-1,4-dimethoxyquinone 4 and the new geranyl-4-methoxyphenyl acetate 5 were obtained by chemical transformations of 1 and 2. The compounds were evaluated for their in vitro cytotoxicity activities against cultured human cancer cells of PC-3 human prostate cancer, MCF-7 and MDA-MB-231 breast carcinoma, and Dermal Human Fibroblasts DHF. IC50 values were in the µM range.

Using fecal profiles of bile acids to assess habitat use by threatened carnivores in the Maulino forest of central Chile

El uso del habitat por carnivoros puede ser examinado a partir de la distribucion de sus huellas y fecas. Para que ambas aproximaciones sean usadas en forma segura y complementaria, ellas deberian no solamente discriminar inequivocamente entre especies, sino que tambien deberian entregar la misma informacion sobre los patrones de distribucion espacial. Analizamos el cumplimiento de estos requisitos con cinco especies de carnivoros en el bosque maulino de Chile central: Galictis cuja, Oncifelis guigna, Pseudalopex culpaeus, Pseudalopex griseus y Puma concolor. Los perfiles de acidos biliares fecales, establecidos mediante cromatografia de capa fina, resultaron ser especie-especificos, invariantes tanto dentro de muestras de un mismo individuo como entre muestras de diferentes individuos de una misma especie, pero son consistentemente diferentes entre especies. La distribucion especial de fecas en areas de bosque nativo y plantaciones de pino en el bosque costero del Maule se comparo con la distribucion esperada en base a estudios previos basados en registro de huellas. Pseudalopex culpaeus usa extensamente plantaciones de pino; Oncifelis guigna prefiere bosque nativo y Pseudalopex griseus usa bosque nativo y plantaciones de pino en proporcion a su disponibilidad. Los resultados de la distribucion de fecas son similares a los obtenidos por registro de huellas

EVALUATION OF THE ANTIOXIDANT CAPACITY OF Psoralea glandulosa L. (Fabaceae) EXTRACTS

The antioxidant properties of different extracts of culen (Psoralea glandulosa L., Fabaceae) herb from Gran Valparaiso location in Chile were evaluated. Antioxidant capacity was assessed in four different model systems. Antioxidant models were examined by measuring the scavenging activity of extracts on 2,2-diphenyl-1-pycrylhydrazil (DPPH●) as well as on hydrogen peroxide (H 2 O 2 ), the oxidant species. In addition, extracts were evaluated by ferric reducing antioxidant power (FRAP) and the total peroxyl radical-trapping potential (TRAP). The amount of dried extract, the content of total phenolics, flavonoids and hydrolyzed sugar were also determined. The leaves extracts from culen expressed very strong scavenging activity, reducing the DPPH● (IC 50 = 1.00 mg/mL to 1.61 mg/mL) and neutralizing H 2 O 2 (IC 50 = 34.29 mg/mL to 64.87 mg/mL). Also, dichloromethane extract of the leaves showed notable index of FRAP (2.71 mM) and TRAP (1.19 mM). The results suggest strong antioxidant potential of dichloromethane and ethyl acetate extracts of leaves of P. glandulosa that could be partially explained by the levels of phenolics (1.65 mg GAE/g dry extract) and flavonoids (55.34 mg QE/g dry extract) respectively.

PHENOLICS, DEPSIDES AND TRITERPENES FROM THE CHILEAN LICHEN PSEUDOCYPHELLARIA NUDATA (ZAHLBR.) D.J. GALLOWAY

The lichen Pseudocyphellaria nudata is a species endemic to southern South America. From the lichen tallus, methyl orsellinate, 2-methoxy-3,6-dimethyl4-hydroxybenzaldehyde, methyl-evernate, tenuiorin, hopan-6s,22-diol and hopan-6α,7s,22-triol were isolated and identified as the main lichen constituents. This is the first report of the occurrence of 2-methoxy-3,6-dimethyl-4-hydroxybenzaldehyde in lichens.

Factores Bióticos y Concentración de Ácido Carmínico en la Cochinilla (Dactylopius coccus Costa) (Homoptera: Dactylopiidae)

A B S T R A C T The cochineal insect, Dactylopius coccus Costa (Homoptera: Dactylopiidae), grows on the pricklypear cactus, Opuntia ficus-indica (L.) Mill. (Cactaceae), and is exploited for its capacity to produce natural dyes based on carminic acid. Cochineal insects were introduced in Chile in 1989, and exports of dry cochineal began in 1994 and grew to cover approximately 15% of the world market. However, the current price of dry cochineal is nearing production costs; hence, it has become necessary to increase yields without increasing costs. This work reports on the effect of biotic factors on the concentration of carminic acid (CAC) in cochineal insects. CAC was positively affected by the density of cochineal insects around the insect, that was analyzed by plant age, and by the nutritional status of the plant, and was negatively affected by the age of the cladode. Additionally, CAC was significantly affected by season: 16.9% of dry weight in the Autumn and 19.1% in the Spring. This knowledge may be used in designing cultural strategies to increase carminic acid accumulation in cochineal insects.