El genero Discaria (fam. Ramnaceas) ha sido estudiado con atencion en su contenido alcaloidal. La polimorfica especie Discaria serratifolia, ha sido exhaustivamente analizada desde el punto de vista sistematico. Ambas situaciones nos han llevado a analizar el contenido de alcaloides bencilisoquinolinicos, buscando una correlacion con la clasificacion. De las ramas de Discaria serratifolia var. foliosa se aislo un alcaloide comun en el genero, R-(—)-O-metilarmepavina. En cambio de las ramas de Discaria serratifolia var. montana se caracterizo una aporfina nueva para la ciencia, la S-(+)-1 ,2-dime-toxi-I 1 -hidroxiaporfina (1) que es el primer ejemplo de una aporfina en el genero.

The intracellular bacteria Piscirickettsia salmonis is the most prevalent pathogen in the Chilean salmon industry, responsible for 50% of losses in recent years. So far, there are no effective treatments to control infections by this pathogen due to the emergence of antibiotics resistance. Therefore, it is extremely important to conduct research to find successful antibacterial therapies. In this paper, we evaluated the in vitro bactericidal activity of flavonoids and aromatic geranyl derivatives isolated from the resinous exudate of species Heliotropium filifolium, H. sinuatum y H. huascoense. The results showed that the compounds Filifolinone, Naringenine and 3-O-methylgalangine cause different percentage of mortality of bacteria and therefore they are good candidates to continue its evaluation in vitro and in vivo.

La bacteria intracelular Piscirickettsia salmonis es el patogeno de mayor incidencia en la industria salmonera chilena siendo responsable de un 50% de las perdidas en los ultimos anos. Hasta ahora no hay tratamientos efectivos para este patogeno que permitan controlar las infecciones provocadas por el debido a la aparicion de resistencia a antibioticos. Por lo tanto, resulta de gran importancia investigar para encontrar terapias antibacterianas efectivas. En este trabajo nosotros evaluamos la actividad bactericida in vitro de flavonoides y derivados aromaticos geranilados aislados desde el exudado resinoso de las especies vegetales Heliotropium filifolium, H. sinuatum y H. huascoense. Los resultados mostraron que los compuestos Filifolinona, Naringenina y 3-O-metilgalangina provocan diferentes porcentajes de mortalidad de la bacteria y, por lo tanto, son candidatos para seguir siendo evaluados tanto in vitro como in vivo

The intracellular bacteria Piscirickettsia salmonis is the most prevalent pathogen in the Chilean salmon industry, responsible for 50% of losses in recent years. So far, there are no effective treatments to control infections by this pathogen due to the emergence of antibiotics resistance. Therefore, it is extremely important to conduct research to find successful antibacterial therapies. In this paper, we evaluated the in vitro bactericidal activity of flavonoids and aromatic geranyl derivatives isolated from the resinous exudate of species Heliotropium filifolium, H. sinuatum y H. huascoense. The results showed that the compounds Filifolinone, Naringenine and 3-O- methylgalangine cause different percentage of mortality of bacteria and therefore they are good candidates to continue its evaluation in vitro and in vivo.

Four 3H-spiro1-benzofuran-2, 1'-cyclohexanes were synthesized from filifolinol, two of which are reported for the first time. Docking molecular studies were carried out to determine in silico whether these derivatives have similar immunostimulant activity to that reported for filifolinol, and its oxidation product, filifolinone. Through of the study of interactions of these compounds with the heterodimer of the protein present in teleost TLR1-TLR2, filifolinol, 3'-filifolinchloride and filifolinyl acetate shows similar interactions between them, allowing to predict that they would have similar immunostimulant activity, but different to filifolinone and filifolinane or that they would act by a different mechanisms.

Fish farming crops are constantly exposed to infectious diseases due to intensive production conditions under which microorganisms develop and spread easily, resulting in severe economic losses. The massive use of antibiotics to control these diseases has lead to the accumulation of residues and the development of drug resistance. Consequently, it is urgent to develop new pharmacological tools to stimulate protective immune responses in salmonids to combat infectious diseases. We evaluated the immunostimulant activity of terpenoid derivatives isolated from species of the Heliotropium genus, which had previously shown antiviral activity in salmon. The immunomodulatory effects of the 3 H-spiro [1-benzofuran-2,1'-ciclohexane] derivative called filifolinone, were studied in vitro using the SHK-1 cell line derived from leucocytes of salmon head kidney and in vivo in Atlantic salmon. For the evaluation, we studied the effect of this compound in the expression of various cytokines. The results showed that Filifolinone increases the levels of expression of pro-inflammatory and anti-inflammatory cytokines. This suggests that Filifolinone is a potential alternative immunomodulator for veterinary purposes.

Several natural compounds containing a coumarin moiety have been reported. They have multiple biological activities, e. g., as scavengers of reactive oxygen species (ROS) and to reduce the inflammatory processes by inhibition of enzymes like COX or LOX.A study was made of the inhibitory capacity of seven natural coumarins and one derivative of esculetin, against soybean 15-lipoxygenase (15-sLOX). The studied coumarins showed interesting degrees of inhibition compared to quercetin, a known LOX inhibitor. Docking studies of some compounds into the binding site of 15-sLOX and 5-hLOX were also made.

The Complement system is a phylogenetically conserved element which emerged about 600-700 million years ago, preceding antibody development, and evolved as a sophisticated, distinct and important part of the innate immune system, reflecting its relevance in protection against non-self. Several diseases involve improper activation of the Complement system (Alzheimer’s disease; rheumatoid arthritis; multiple sclerosis, etc.). Hyperacute rejection of transplants, isquemia reperfusion and others pathologies also take place with an unregulated response of this system. Unfortunately, only few drugs are available to treat disorders based on Complement system, and none of them can be administrated orally. Synthesis is one of the most relevant methodologies to opitmize the pharmacological profile of an active molecule. In this context, we have been able to produce new derivatives of filifolinol (1), a natural product structurally reminiscent of the well established Complement inhibitor K-76 (2, isolated form Stachybotrys complementii) and its acid derivative (3). We have synthesized (Figure 1) filifolinol derivatives modified on C3’ and C7 with improved bioactivity (4-6).

A series of carboxylic acids carrying various functionalization on C-7 of their common 3H-spiro [benzofuran-2,1'-cyclohexane] skeleton were synthesized from filifolinol, as analogs of the natural Complement inhibitor K-76 COOH. In order to probe the relevance of the C-7 functionalization on their bioactivity, the ability of the analogs to inhibit Complement activation through the classical pathway was determined. The observed results suggest that functionalization of C-7 can modulate the inhibitory activity of the tested compounds. The 7-trifluoromethyl derivative was the compound with the lowest IC50 value among the tested analogs (IC50 = 100 mu M), being more potent than K-76 COOH (IC50 = 570 mu M). (C) 2012 Elsevier Masson SAS. All rights reserved.

The in vitro effect of the 3 H-spiro [1-benzofuran-2,1'-ciclohexane] derivative (Filifolinone), was evaluated on mouse dendritic cells through the level of expression of MHC molecules class II by flow cytometry. The results show that Filifolinone increases the expression of MHC promoting maturation of dendritic cells. The results suggest that Filifolinone is a potential immunomodulator for veterinary use.

The in vitro effect of the 3 H-spiro [1-benzofuran-2,1’-ciclohexane] derivative (Filifolinone), was evaluated on mouse dendritic cells through the level of expression of MHC molecules class II by flow cytometry. The results show that Filifolinone increases the expression of MHC promoting maturation of dendritic cells. The results suggest that Filifolinone is a potential immunomodulator for veterinary use.

In this report we study the seasonal variation of the flavonoids pinocembrin and 3-O-methylgalangin in the surface component mixture (resinous exudate and waxy coating) of Heliotropium stenophyllum. The quantitative analysis of the flavonoids was performed using high-performance liquid chromatography of samples collected monthly over a whole year. The results showed an increase in the spring and summer yield of surface components and a decrease during the winter. Although the sum of pinocembrin and 3-O-methylgalangin did not follow a pattern related with hydric stress, UV radiation or high temperature during the year, a relationship between pinocembrin and 3-O-methylgalangin was found. On average during the months of September to August, excluding March, the amount of pinocembrin decreased wile the amount of 3-O-methylgalangin increased. The results suggest that the above compounds may play different ecophysiological functions during plant development and are consistent with the biosynthetic relationship between the two compounds.

The in vitro effect of the resinous exudate of Heliotropium filifolium, of the 3 H-spiro[1-benzofuran-2,1'-cyclohexane] derivative called filifolinol 1, isolated from the resin and the semi-synthetic compounds filifolinone 2 and filifolinoic acid 3, obtained from filifolinol 1, were evaluated on the proliferation of an immortalized cell line, UCHT1, derived from rat thyroid. We evaluated the effect of these compounds on UCHT1 cell growth parameters by calculating doubling time; and toxicity using the LIVE/DEAD (TM) in vitro test. The results showed that the resin is not active, while filifolinone 2, filifolinoic acid 3 and filifolinol 1 produced a significant inhibition of cell doubling time, in concentrations equal or greater than 50, 25 and 75 mu M, respectively. The LIVE/DEAD test showed no significant toxicity at these concentrations, compared to cultures kept in absence of compounds. These results suggest a possible cytostatic effect of these compounds, and could therefore constitute potential alternatives for antineoplasic therapy.

Chromatography on the resinous extract of aerial parts of Haplopappus remyanus led to the isolation of 18-acetoxy-labda-7,13E-dien-15-oic acid along with the monoterpene derivatives 9-hydroxy-α-terpineol, 9-benzoyloxy-α-terpineol,7-hydroxy-9-benzoyloxy-α-terpineoland 9-benzoyloxy-(1-formyl)-α-terpineol. Structures for the new compounds are proposed on spectroscopic evidence. The presence of quercetin and five other known flavonoids identified in this study could account for the reported high antioxidant activity and the moderate topic anti-inflammatory effect on induced ear oedema. MTT assay with CCRF-CEM tumor cells showed 50% of the cytotoxic activity displayed by doxorubicin under the same conditions. Quantitative differences in chemical composition were detected in comparison with previous studies of the species that could be attributed to environmental factors.

Infectious pancreatic necrosis is a disease caused by a birnavirus affecting several wild and commercial aquatic organisms. This infectious disease results in significant losses in the farming industry and therefore effective therapeutic agents are needed to control outbreaks caused by this pathogen. Our goal was to evaluate in vitro antiviral effect of a group of natural compounds (geranyl aromatic derivatives) isolated from the resinous exudate of the plant Heliotropium filifolium (Heliotropiaceae), semi-synthetics compounds obtained from them, and the resinous exudate, on CHSE-214 cell line infected with infectious pancreatic necrosis virus (IPNV) using a virus plaque inhibition assay at various concentrations. The compound ester filifolinyl senecionate was the best antiviral with EC(50) 160 mu g/mL and a cytotoxic concentration required to reduce cell viability by 50% up to 400 mu g/mL. In order to obtain information about the mechanism of the antiviral action, was evaluated the influence of ester filifolinyl senecionate on the viral RNA synthesis. This compound produced inhibition of the synthesis of viral genomic RNA, suggesting that the ester could be interacting with the viral RNA during the viral cycle. Additionally, a preliminary study of the interaction between ester and a sample of single-stranded RNA was studied at the level of theory Restricted Hartree Fock PM3 method. The results showed that the ester formed hydrogen bonds mainly with nitrogenous bases but not with ribose and phosphate.These results allow propose that the ester filifolinyl senecionate is a good candidate for used as antiviral therapy for IPN virus in salmon fry. (C) 2009 Elsevier B.V. All rights reserved.

Heliotropium sclerocarpum Phil. (Heliotropiaceae) is a resinous bush that grows in the Atacama of northern Chile. The chemical composition of its resinous exudate was analyzed for the first time. One aromatic geranyl derivative: filifolinol (1), one flavanone: naringenin (2) and a new type of 3-oxo-2-arylbenzofuran derivative 3 were isolated and their structures were determined. The antioxidant activity of the phenolic compounds and resin was evaluated using the bleaching of DPPH radical method and expressed as fast reacting equivalents (FRE) and total reacting equivalents (TRE).

A new series of tricyclic carboxylic acids with a 3H-spiro[benzofuran-2,10-cyclohexane] skeleton were synthesized from filifolinol, as analogs of the natural complement inhibitor K76-COOH. Their complement inhibitory activity was determined aiming to probe the importance of structural characteristics of the alicyclic part of K76-COOH. The presence and stereochemistry of O- and N-functionalities on C3' of the filifolinol derivatives are relevant for biological activity. The IC50 values of the most potent compounds were comparable or surpassed the activity of K76-COOH. The results also suggest that the diol moiety of the natural product may be useful for improving compound solubility.

C19H24O4, monoclinic, P2(1) (no. 4), a = 9.231(2) angstrom, b = 16.318(3) angstrom, c = 11.647(2) angstrom, beta = 91.31(3)degrees, V = 1753.9 angstrom(3), Z = 4, R-gt(F) = 0.045, wR(ref)(F-2) = 0.124, T = 293 K.