The resin of the tree Araucaria araucana (Araucariaceae) is used by the Mapuche Amerindians in southern Chile and Argentina to treat ulcers and has been shown to display a gastroprotective effect in animal models. A study was undertaken to isolate, identify and assess the gastroprotective effect of the resin constituents and its semisynthetic derivatives as well as to evaluate the cytotoxicity of the products in cell cultures. Eleven diterpenes (ten labdane and a pimarane) were isolated from a resin sample collected in Chile. The labdane derivatives 15-acetoxylabd-8(17)-en-19-ol as well as 15,19-diacetoxylabd-8(17)-en are reported for the first time as natural products. Six diterpenes previously described from other plant sources are reported for the first time for the A. araucana resin. The structure of all compounds was elucidated by spectroscopic means. Some 24 diterpenes isolated/prepared in amounts over 10 mg were evaluated for gastroprotective effects in the ethanol/HCl-induced ulcer model in mice at 100 mg/kg. The highest gastroprotective activities were provided by 15-hydroxyimbricatolal, 15-acetoxyimbricatolal, 15-acetoxylabd-8(17)-en-19-oic acid methyl ester and 15-acetoxy-19-labdanoic acid, all of them being as active as the reference drug lansoprazole at 20 mg/kg. The cytotoxicity of 30 diterpenes as well as lansoprazole was assessed towards human lung fibroblasts (MRC-5) and 26 compounds were evaluated on the human gastric epithelial cell line AGS by means of the neutral red uptake assay. A concentration-dependent cell viability inhibition was found with IC 50 values ranging from 27 up to > 1000 µm. The relationship between the cytotoxicity data and lipophilicity of the products is also discussed.

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Abstract:In this work a detailed analysis of the temporal evolution of the Almegíjar landslide is presented. It is a rock slide located in the Alpujarras region (Granada, Spain) that has developed over the last 30 years. Six datasets and photogrammetric flights corresponding to the years 1956, 1984, 1992, 2001, 2008, and 2010 were surveyed. The more recent flight of 2010 combined an aerial digital camera and a LiDAR sensor and was oriented by means of in-flight data and tie points. This 2010 flight allowed for the generation of a reliable and high-precision Digital Terrain Model (DTM). The other flights were oriented using second-order ground control points transferred from the 2010 flight, and the corresponding DTMs were prepared by automatic matching and subsequent editing from the stereoscopic models. After comparing the DTMs of different dates, it has been observed that the landslide was triggered after 1984 and since then has evolved in an irregular pattern with periods of variable activity. On average, the ground surface dropped more than 8 m in depleted zones and rose nearly 4 m in the accumulation zones, with a velocity catalogued as very slow (about 15-30 cm/year) over a time span corresponding to a degree VIII of diachroneity. The total volume of the mobilized mass of this large contemporary slide was about 300 × 10 3 m 3 .

There is continuing and emerging new interest in the development of vitamin D analogs resulting from the recognition that analogs of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] may be therapeutically useful. Side chain analogs of this steroid hormone are of particular interest because a family of lead structures have recently emerged for possible use in the treatment of certain types of cancers and skin diseases. Because of the chaotic array of side chain structures which exhibit useful therapeutic indices for these purposes, a more systematic approach towards developing intelligible structure-function information needs development. Accordingly, a method has been devised to analyze analogs as to their side chain topology based on identifying specific occupancy volumes through conformational analysis. Dot maps have been constructed as an indication of the volume in space which the side chain of 1 alpha,25-(OH)2-D3 or analogs is permitted to occupy. Volume exclusion analyses based on comparison of structural and biological data for 1 alpha,25-(OH)2-D3 and analogs are anticipated to lead to a more cogent model for drug design. A cautionary note on the limitations of this approach is discussed.

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Some 18 aromatic amides from the labdane diterpenes 15-acetoxyimbricatolic acid and 15-acetoxylabd-8(9)-en-19-oic acid were prepared and assessed for their gastroprotective effect in the HCl/EtOH-induced gastric lesion model in mice. The analysis of the gastroprotective activity of the benzylamides belonging to the series 8(9)- and 8(17)-ene was undertaken at doses of 12.5, 25 and 50 mg/kg in the HCl/EtOH-induced gastric lesion model in mice. A statistically significant gastroprotective effect was observed for 15-acetoxylabd-8(9)-en-19-oic acid benzylamide starting at 12.5 mg/kg, reducing the gastric lesions by 50%, while 15-acetoxylabd-8(17)-en-19-oic acid benzylamide reduced lesions by 66% at 25 mg/kg. The 25 mg/kg dose was used for the comparison of the different amides. At 25 mg/kg, the highest gastroprotective effect was observed for the benzyl- and 3-bromophenylamides from 15-acetoxyimbricatolic acid as well as for the benzyl- and P-toluidylamides of 15-acetoxylabd-8(9)-en-19-oic acid, being as active as lansoprazole at 20 mg/kg. Most compounds displayed low toxicity against epithelial gastric (AGS) and human lung fibroblasts cells, with IC50 values>1000 microM. The highest cytotoxicity towards AGS cells was observed for the 2-bromophenyl- and 2-hydroxy-5-chlorophenylamides in both diterpene series, with IC50 values in the range of 14-34 microM towards AGS cells and 10-37 microM towards fibroblasts, respectively.