Marco Mellado

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.

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.

2D-QSAR and 3D-QSAR/CoMSIA Studies on a Series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-Phenylethan-1-ol with Human β3-Adrenergic Activity

The β3 adrenergic receptor is raising as an important drug target for the treatment of pathologies such as diabetes, obesity, depression, and cardiac diseases among others. Several attempts to obtain selective and high affinity ligands have been made. Currently, Mirabegron is the only available drug on the market that targets this receptor approved for the treatment of overactive bladder. However, the FDA (Food and Drug Administration) in USA and the MHRA (Medicines and Healthcare products Regulatory Agency) in UK have made reports of potentially life-threatening side effects associated with the administration of Mirabegron, casting doubts on the continuity of this compound. Therefore, it is of utmost importance to gather information for the rational design and synthesis of new β3 adrenergic ligands. Herein, we present the first combined 2D-QSAR (two-dimensional Quantitative Structure-Activity Relationship) and 3D-QSAR/CoMSIA (three-dimensional Quantitative Structure-Activity Relationship/Comparative Molecular Similarity Index Analysis) study on a series of potent β3 adrenergic agonists of indole-alkylamine structure. We found a series of changes that can be made in the steric, hydrogen-bond donor and acceptor, lipophilicity and molar refractivity properties of the compounds to generate new promising molecules. Finally, based on our analysis, a summary and a regiospecific description of the requirements for improving β3 adrenergic activity is given.

ANTIOXIDANT EFFECTS OF MUEHLENBECKIA HASTULATA J. (POLYGONACEAE) EXTRACTS

The antioxidant properties of different extracts of quilo (Muehlenbeckia hastulata J., Poligonaceae) herb from Valparaiso region in Chile were evaluated. Antioxidant activity was assessed in three different model systems. Antioxidant models were examined by measuring the scavenging activity of extracts on 2,2-diphenyl-1-pycrylhydrazil (DPPH●). Moreover 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, hydrolyzed sugar and anthraquinones were also determined. Extracts pertaining to stem and root of the plants were the significant activities DPPH radical scavenging (IC 50 0.74 mg/mL to 1.33 mg/mL the more active extracts). The activities and TRAP and FRAP high values in extracts of EtOAc (1.423 and 1.540 mM TEAC) and ethanol (245.26 and 309.04 mM TEAC) stem and root of the plant are higher.The observed differences in antioxidant activity among the different parts of quilo could be partially explained by the levels of phenolics compounds present in the root extract of EtOAc (0.023 mg GAE/g dry extract), flavonoids in the leaves of EtOAc extract (99.12 mg QE/g dry extract), hydrolyzed sugar in the ethanol extract (21.87, 14.85 and 14.32 mg GES/ g dry extract of leaf, stem and roots, respectively) and anthraquinones in the EtOAc extracts (2.50, 1.43 and 0.84 mg EE/ g dry extract of leaf, stem and roots, respectively) .

PRELIMINARY ANTIPROLIFERATIVE EVALUATION OF NATURAL,-SYNTHETIC BENZALDEHYDES AND BENZYL ALCOHOLS

Vanillin, o-vanillin, natural and synthetic benzaldehydes and benzyl alcohols were assessed for antiproliferative effects using different human cell lines. Benzyl alcohols were synthesized from benzaldehydes reduced with NaBH4 in methanol solution. A new method for deprotection of ether compounds with TiCl4 solution was achieved with better performance, than previously reported. Twenty four compounds were tested. The in vitro growth inhibition assay was based on sulphorhodamine dye to quantify cell viability. Catechol 9 derived from piperonal as well as compounds 4 and 12 showed higher cytotoxicity on breast and prostate cancer cell lines (MDA-MB-231 and PC-3 respectively). o-Vanillin 5 has the highest cytotoxicity for all cell lines. IC50 values of 35.40 ± 4.2 μM Breast MDA-MB231; 47.10 ± 3.8 μM Prostate PC-3; 72.50 + 5.4 μM Prostate DU-145; 85.10 + 6.5 μM and Colon HT-29, were obtained without toxicity towards dermal human fibroblast (DHF cells).

Structure-Activity Relationship of Dialkoxychalcones to Combat Fish Pathogen Saprolegnia australis

To investigate the anti-Saprolegnia activities of chalconic compounds, nine dialkoxychalcones 2–10, along with their key building block 2′,4′-dihydroxychalcone 1, were evaluated for their potential oomycide activities against Saprolegnia australis strains. The synthesis afforded a series of O-alkylated derivatives with typical chalcone skeletons. Compounds 4–10 were reported for the first time. Interestingly, analogue 8 with the new scaffold demonstrated remarkable in vitro growth-inhibitory activities against Saprolegnia strains, displaying greater anti-oomycete potency than the standard drugs used in the assay, namely fluconazole and bronopol. In contrast, a dramatic loss of activity was observed for O-alkylated derivatives 2, 3, 6, and 7. These findings have highlighted the therapeutic potential of the natural compound 1 scaffold to be exploitable as a drug lead with specific activity against various Saprolegnia strains.

Antioxidant, phenolic and antifungal profiles of Acanthus mollis (Acanthaceae).

Abstract Acanthus mollis is used as ornamental and medicinal plant. The ethnopharmacology reports indicate that extracts have anti-inflammatory activity. Phytoconstituents profile was evaluated by estimating the content of anthraquinones, flavonoids and phenols. In addition, the antioxidant activity was evaluated using four methods: Hydrogen atoms transfer (TRAP, ORAC and DPPH assays), and single electron transfer (FRAP assay). Finally, antifungal activity was determined by the M27-A2 test. The results shown that ethanol extracts have the highest concentration of phenols, anthraquinones and flavonoids. Total antioxidant capacity, extracts of ethyl acetate and ethanol are those with the highest activity, which correlates strongly with the presence of phenols. The antifungal activity measured in various strains of Candida is concentrated in ethyl acetate extracts of flower and leaf ethanol, a phenomenon may be related to antioxidant activity.

Free radical-scavenging activity of sequential leaf extracts of Embothrium coccineum

Abstract The aim of this study was to evaluate the influence of phenolic, flavonoid, and anthraquinones from sequential extracts (n-hexane, dichloromethane, ethyl acetate, and ethanol) of Embothrium coccineum leaves on the antioxidant capacity, cell viability, and toxicity of the same, in order to find possible sources for novel antioxidants for food and pharmaceutical formulations. Antioxidant potential of sequential extracts was analyzed by five different assays: 2,2-diphenyl-1- picrylhydrazyl radical scavenging activity assay (DPPH), hydrogen peroxide scavenging activity (H2O2), oxygen radical absorbance capacity (ORAC), ferric reducing antioxidant power (FRAP), and total reactive antioxidant potential (TRAP). An in vitro growth inhibition assay was performed using sulphorhodamine dye to quantify cell viability, while an in vivo brine shrimp lethality test was used to quantify toxicity. The dichloromethane extract has a greater efficiency in scavenging free radicals, combined with low toxicity, and no effect exhibited on healthy cells, compared to observations for the other extracts tested. Further research is in progress to identify and separate the active compounds of active extracts and investigate the protective effect of extracts on human dermal fibroblast injury induced by hydrogen peroxide.