Ent-kaurenic Acid Research Articles

Chemotaxonomic implications of the absence of sesquiterpene lactones in Grazielia multifida (DC.) R.M.King & H.Rob. (Asteraceae)

The phytochemical investigation of Grazielia multifida aerial parts yielded eight compounds, including four ent-kaurenic acid diterpenes derivatives, 15-tiglinoyloxy-ent-kaur-16-en-19-oic acid (1), 15-hydroxy-ent-kaur-16-en-19-oic acid (2), 17-hydroxy-ent-kaur-15-en-19-oic acid (3) and 15-isovaleroyloxy-ent-kaur-16-en-19-oic acid (4), one amino acid, tryptophan (5), and three flavonoids, eupafolin (6), guaijaverin (7) and quercitrin (8). The structures of the isolated compounds were established based on analysis of their spectroscopic data and comparison with literature. All the compounds were isolated from this species for the first time. The chemotaxonomic significance of the absence of sesquiterpene lactones in G. multifida has also been summarized.

In vitro antimicrobial activity of two dibutyltin(IV) complexes of kaurenic acids derivatives

The antimicrobial activity in vitro of ent-kaurenic, KA [1] and grandiflorenic acid, GA [2], two natural products obtained from Espeletia semiglobulata Cuatrec., and two dibutyltin (IV) complexes [3] and [4] derived from natural products synthesis, ent-kaurenic acid and grandiflorenic acid, respectively, against strains of Escherichia coli, Pseudomonas aeruginosa, both pathogens for man, and Trametes versicolor, a fungus responsible of white wood rotting. For the human pathogens, an agar diffusion disk was used, with a 30 µg/mL concentration. There was an improved activity with the dibutyltin(IV) with grandiflorenic acid [4] against E. coli; while the anti-fungal activity against T. versicolor was done by a gel dilution method with surface plate inoculation getting an improved anti-fungal activity with 120 µg/mL concentration. The new compounds were characterized with FTIR spectroscopy, 1H, 13C unidimensional and bidimensional NMR experiments for the natural products [1], [2] and the organotin complexes [3] and [4].

Effect of some ent -Kaurenes on the Viability of Human Peripheral Blood Mononuclear Cells

The possible cytotoxic activity of some ent-kaurenes on human mononuclear cells, obtained from peripheral blood, was studied having in mind future studies on their antitumor activity. The cells were obtained using the Ficoll-Hypaque method, adjusted to 2 x 10(6) cells/mL, and incubated with kaurenes for 48 hours at 3 x 10(-5), 30 x 10(-5), 300 x 10(-1) and 3000 x 10(-5) micromol/well. Ent-kaurenic acid showed no toxicity at all concentrations studied. The least toxic of all the kaurene derivatives studied was ent-15,16-epoxy-17-acetoxy-(-)-kauran-19-oic acid, with a cellular viability of 99% at 3 x l0(-5) micromol/well, and 94% at 30 x 10(-1) micromol/well. Another compound that showed low toxicity was the 2,3,4,6-tetra-acetyl-alpha-D-pyranosyl ester of ent-15-oxo-(-)-kaur-16-en-19-oic acid with 44% viability at 3000 x 10(-5) micromol/well. The most toxic compounds at all concentrations tested were ent-kaur-16-en-19-ol acetate and ent-16alpha-hydroxy-(-)-kauran-19-oic acid. On the other hand, ent-kaur-9(11)16-dien-19-oic acid, ent-kauran-19-oic acid, and ent-kaur-16-en-19-ol were toxic only at the highest concentration studied. According to these results, and considering the concentrations employed, ent-kaur-16-en-19-oic acid and ent-15,16-epoxy-17-acetoxy-(-)-kauran-19-oic acid could be used for in vivo experiments and possibly for therapeutic purposes on humans, without much risk.

Cytotoxic and apoptosis-inducing effect of ent-15-oxo-kaur-16-en-19-oic acid, a derivative of grandiflorolic acid from Espeletia schultzii

ent-Kaurenic acid and many natural derivatives of this diterpene are known to have interesting biological properties. ent-15-Oxo-kaur-16-en-19-oic acid can be easily obtained from grandiflorolic acid which was first isolated from Espeletia grandiflora. The present work describes the proapoptotic effect of ent-15-oxo-kaur-16-en-19-oic acid on the human prostate carcinoma epithelial cell line PC-3 as evidenced by the changes in the expression level of proteins associated with the execution and regulation of apoptosis. Cell viability was affected upon exposure to the compound, the IC 50 were determined as 3.7 μg/ml, which is 4 times lower than that corresponding to a primary cell culture of fibroblasts (14.8 μg/mL). Through Western blot analysis, active forms of caspace-3 associated with the specific proteolysis of Poly(ADP-ribose) polymerase (PARP) were detected. Reduced levels of the antiapoptotic protein Bcl-2, as well as the appearance of internucleosomal DNA fragmentation, were also demonstrated. Thus, ent-15-oxo-kaur-16-en-19-oic acid may be a promising lead compound for new chemopreventive strategies, alone or in combination with traditional chemotherapy agents to overcome drug resistance in tumoral cells.

Yacon [Smallanthus sonchifolia (Poepp. et Endl.) H. Robinson] chemical composition and use - a review

Yacon [Smallanthus sonchifolia (Poepp. et Endl.) H. Robinson], a native plant of the Andes, belongs to the family Compositae (Asteraceae) and it represents a traditional crop of the original population of Peru used in traditional medicine. A major portion of tuberous root biomass is composed of water (> 70% of fresh weight). Saccharides, especially oligo-fructans, form 70–80% of dry weight, protein content ranges between 0.3% and 3.7%. Fructooligosaccharides of inulin type b (2®1), mainly oligomers (GF2–GF16), are known for their ability to keep the colon healthy. Yacon sweetness is predominantly caused by fructose, which is by some 70% sweeter than sucrose. Other oligosaccharides are 1-kestose and nystose. Diabetics and persons suffering from digestive problems are recommended to consume yacon because its sugars are not available from the small intestine. The mean tuberous root composition per 100 g of fresh matter is 81.3, 13.8, 0.9, 1.0, 0.1 and 1.1 g of water, saccharides, fibre, proteins, lipids and ash, respectively. Mean mineral contents per 100 g of fresh matter are 334, 34, 12, 8.4, 0.4 and 0.2 mg of potassium, phosphorus, calcium, magnesium, sodium and iron, respectively. Vitamins B1, B2, C, b-carotene and polyphenols in the same weight are present at mean concentrations 0.07, 0.31, 5.0, 0.13 and 203 mg, respectively. Yacon can be considered an industrial crop, particularly as a source of inulin. The used forms are flour, syrup, extract from tuberous roots and moreover leaf extract for the preparation of yacon infusion with hypoglycaemic effect. In yacon leaves di- and sesquiterpenes with protective effects against insects are present, among them mainly ent-kaurenic acid (ent-kaur-16-en-19-oic acid) and its derivative – 15-a-angeloyloxy-ent-kauren-19-oic acid 16-epoxide. Other components are polyphenolic antioxidants, esp. hydroxycinnamic acids and chlorogenic acid. A new antifungal melampolide – sesquiterpene lactone named sonchifolin, as well as three known melampolides, polymatin B, uvedalin and enhydrin, were isolated from leaf extracts of yacon. Three major phytoalexins were isolated: 4’-hydroxy-3’-(3-methylbutanoyl)acetophenone, 4’-hydroxy-3’-(3-methyl-2-butenyl)acetophenone and 5-acetyl-2-(1-hydroxy-1-methylethyl)benzofuran.

New Eudesmanolide Sesquiterpenes from a Philippines Collection of Wedelia prostata

Two known, but previously uncharacterized, ent-kaurenic acid derivatives, 1 and 2, and four new sesquiterpenes of the eudesmanolide type, 3-6, have been isolated from Wedelia prostata. The structures were eludidated by a range of 1D and 2D high field nmr techniques, and the stereochemistry of the new eudesmanolides was defined from a combination of coupling constant analyses and nuclear Overhauser difference spectra

Ent-kaurenic Acid and Its Related Compounds from Glandular Trichome Exudate and Leaf Extracts ofPolymnia sonchifolia

Yacon (Polymnia sonchifolia) leaves possess glandular trichomes on the surface. The exudate from the glandular trichome and the leaf are itself rich in ent-kaurenic acid (ent-kaur-16-en-19-oic acid). A kaurene derivative, 15-α-angeloyloxy-ent-kauren-19-oic acid 16-epoxide, was isolated from the leaves, together with two known angeloyloxykaurenic acids. The high content of ent-kaurenic acid in the leaf suggests that these diterpenes play a certain physiological role, since the glandular trichome exudates of other species function in their defensive mechanism.

Some sesqui- and diterpenes from the tribe eupatorieae

The aerial parts of Trichogonia salviaefolia afforded a new ent-kaurenic acid derivative and a germacranolide which, most likely, is the precursor of the trichosalviolides. The aerial parts of Liatris spicata gave 1α-hydroxybacchotricuneatin A and a guaianolide, which may be the precursor of spicatin. From Brickellia vernicosa some further dehydronerolidol derivatives were isolated.

Eudesmanolides and kaurene derivatives from Wedelia hookeriana

From the aerial parts of Wedelia hookeriana eight new eudesmanolides, all derivatives of ivangustin, and a new ent-kaurenic acid derivative togethe

15α-Methylacryloyloxy- ent-kaurenic acid from Ichthyothere species

15α-Methylacryloyloxy- ent-kaurenic acid from Ichthyothere species

Eudesmanolides and diterpenes from Wedelia trilobata and an ent-kaurenic acid derivative from Aspilia parvifolia

The reinvestigation of the aerial parts of Wedelia trilobata afforded, in addition to known compounds, six new eudesmanolides, two ent-kaurenic acid derivatives as well as a degraded one. A corresponding hydroxy compound was present in Gnaphalium undulatum. From Aspilia parvifolia new ent-kaurenic acid epoxides were isolated. The structures were elucidated by spectroscopic methods. The chemotaxonomic situation is discussed briefly.

Neue ent-atisiren- und ent-kaurensäure-derivate aus Helianthus-arten

The investigation of four Helianthus species afforded, in addition to known compounds, four new atisirenic acid derivatives, a new ent-kaurenic acid derivative, three new labdane derivatives and an unknown C 15-acetylenic compound. The structures of the diterpenes were elucidated by intensive NMR studies and some chemical transformations. An unusual fragmentation in the mass spectra of the atisirenes is discussed briefly.

Helifulvanolsäkure—ein neues diterpen mit anomalem kohlenstoffgerüst aus Helichrysum fulvum

The aerial parts of Helichrysum fulvum afforded, in addition to beyerenic acid and ent-kaurenic acid, two new diterpenic acids with the hitherto unknown carbon skeleton of an isotrachylobane type. The structures of these acids, isolated as their methyl esters, were elucidated by extensive NMR studies, some chemical transformations and by X-ray structural analysis of the corresponding acetate. The related alcohol on reaction with pyridinochlorochromate afforded a homoconjugated diene probably formed by fragmentation of a cyclopropyl carbinol. The possible biogenesis of the new carbon skeleton is discussed briefly.