Antigiardial activity of triterpenoids from root bark of Hippocratea excelsa.

Two new triterpenoids, 21 beta-hydroxyolean-12-en-3-one (1) and a seco-dinor derivative of pristimerine named dzununcanone (2), were isolated from the root bark of Hippocratea excelsa. Their structures were assigned on the basis of spectroscopic evidence, mainly 1H and 13C 1D and 2D NMR including DEPT, COSY, ROESY, HSQC, and HMBC experiments, as well as EIMS and HREIMS. The known 21alpha-hydroxy-3-oxofriedelane (3), a compound new to the species, and the known methide quinones pristimerine (4) tingenone (5), and xuxuarine Ebeta (7) were also isolated. The antiprotozoal activities were determined against Giardia intestinalis. Pristimerine and tingenone were the most active antigiardial compounds, with IC50 values of 0.11 and 0.74 microM, respectively, compared with metronidazole, the current drug of choice (IC50 1.23 microM).

Dihydro-beta-agarofuran sesquiterpenes: a new class of reversal agents of the multidrug resistance phenotype mediated by P-glycoprotein in the protozoan parasite Leishmania.

Leishmaniasis is the most important emerging and uncontrolled infectious disease and the second cause of death among parasitic diseases, after Malaria. One of the main problems concerning the control of infectious diseases is the increased resistance to usual drugs. Overexpression of P-glycoprotein (Pgp)-like transporters represents a very efficient mechanism to reduce the intracellular accumulation of drugs in cancer cells and parasitic protozoans, thus conferring a multidrug resistance (MDR) phenotype. Pgps are active pumps belonging to the ATP-binding cassette (ABC) superfamily of proteins. The inhibition of the activity of these proteins represents an interesting way to control drug resistance both in cancer and in infectious diseases. Most conventional mammalian Pgp-MDR modulators are ineffective in the modulation of Pgp activity in the protozoan parasite Leishmania. Consequently, there is a necessity to find effective modulators of Pgp-MDR for protozoan parasites. In this review we describe a rational strategy developed to find specific Pgp-MDR modulators in Leishmania, using natural and semisynthetic dihydro-beta-agarofuran sesquiterpenes from Celastraceae plants. A series of these compounds have been tested on a MDR Leishmania tropica line overexpressing a Pgp transporter to determine their ability to revert the resistance phenotype and to modulate intracellular drug accumulation. Almost all of these natural compounds showed potent reversal activity with different degrees of selectivity and a significant low toxicity. The three-dimensional quantitative structure-activity relationship using the comparative molecular similarity indices analysis (CoMSIA), was employed to characterize the requirements of these sesquiterpenes as modulators at Pgp-like transporter in Leishmania.

Anti-tumor promoting effects of sesquiterpenes from Maytenus cuzcoina (Celastraceae).

Ten sesquiterpenoids (1-10), with a dihydro-beta-agarofuran skeleton, were isolated from Maytenus cuzcoina (Celastraceae). Their structures were elucidated on the basis of spectral analysis, including homo- and heteronuclear correlations NMR experiments (COSY, ROESY, HMQC and HMBC), and chemical correlations. The compounds have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as a test for potential cancer chemopreventive agents. Compounds 1-3, 6 and 7 showed strong inhibitory effects on EBV-EA induction (100% inhibition at 1000 mol ratio/TPA). Their structure-activity relationship is discussed.

New terpenoids from Maytenus blepharodes.

Three new terpenoids, xuxuarine Ealpha (1), a triterpene dimer based on two pristimerin units, and two sesquiterpenoids with a dihydro-beta-agarofuran skeleton (2 and 3) were isolated from Maytenus blepharodes. Their structures were elucidated on the basis of spectral analysis, including homonuclear and heteronuclear correlation NMR experiments (COSY, ROESY, HMQC, and HMBC). The absolute configurations of 1 and 2 were determined by CD studies.

New natural sesquiterpenes as modulators of daunomycin resistance in a multidrug-resistant Leishmania tropica line.

The effects produced by nine dihydro-beta-agarofuran sesquiterpenes isolated from Crossopetalum tonduzii (1-8) and Maytenus macrocarpa (9) (Celastraceae) on the reversion of the resistant phenotype on a multidrug-resistant Leishmania line and their binding to recombinant C-terminal nucleotide-binding domain of Leishmania P-glycoprotein-like transporter were studied. The structures of the new compounds (1-5) were elucidated by spectroscopic methods, including (1)H-(13)C heteronuclear correlation (HMQC), long-range correlation spectra with inversal detection (HMBC), ROESY experiments, and chemical correlations. The absolute configuration of one of them (1) was determined by CD studies. The structure-activity relationship is discussed.

Triterpene trimers from Maytenus scutioides: cycloaddition compounds?

Two novel trimers, triscutins A and B (1 and 2), based on pristimerin triterpene units, were isolated and characterized from Maytenus scutioides. Their structures were determined on the basis of spectroscopic evidence, including 1H-13C heteronuclear correlation (HMQC), long-range correlation with inverse detection (HMBC), and ROESY NMR experiments; and their absolute configurations, by means of CD studies. Compounds 1 and 2 were assayed for antimicrobial and cytotoxic activities, and their possible biosynthetic route is proposed.

A new antibiotic nortriterpene quinone methide from Maytenus catingarum.

15alpha-Hydroxy-21-keto-pristimerine (1), a new nortriterpene quinone methide was isolated from the root bark of Maytenus catingarum along with other well-known related compounds, including pristimerine (2), tingenone, and 20alpha-hydroxy-tingenone. The structure of 1 was determined by means of 1H and 13C NMR spectroscopy, including homonuclear and heteronuclear correlations. Compound 1 showed antibiotic activity against Gram-positive bacteria.

A new bioactive norquinone-methide triterpene from Maytenus scutioides.

By antimicrobial and cytotoxic-guided fractionation, a bioactive norquinone-methide triterpene, 15 alpha-hydroxypristimerin, was isolated from a South American medicinal plant, Maytenus scutioides. Its structure was determined on the basis of spectroscopic evidence. Successful chemical transformation of pristimerin to netzahualcoyene indicates that the 15-hydroxy compounds seems to be a possible percursor of 14(15)-ene-quinone-methide-triterpenoids in the biogenetic pathway.

Biological activities of some Argyranthemum species.

Seven species of the genus Argyranthemum were studied for antimicrobial and cytotoxic activities. Argyranthemum adauctum, A. foeniculaceum and A. frutescens showed antimicrobial activity against Gram-positive and Gram-negative and cytotoxic activity against HeLa and Hep-2 cell lines. Two new acetylenic compounds, frutescinol isovalerate and 3'-demethyl frutescinol isovalerate, were isolated from A. frutescens and their structures elucidated by spectroscopic studies.

Antibiotic phenol nor-triterpenes from Maytenus canariensis.

The new phenols 6-oxo-tingenol, 3-O-methyl-6-oxo-tingenol and 6-oxo-iguesterol were isolated from the root bark of Maytenus canariensis. Their structures were determined by 1H and 13C NMR spectroscopic studies, including HMQC, HMBC, DEPT and ROESY and chemical transformations. The synthesis of 6-oxo-tingenol was achieved from tingenone. These compounds exhibit antibiotic activity against Gram-positive bacteria.

Scutione, a new bioactive norquinonemethide triterpene from Maytenus scutioides (Celastraceae).

Scutione (1), a new norquinonemethide triterpene with a netzahualcoyene type skeleton, has been isolated from the root bark of Maytenus scutioides (Celastraceae) by bioactivity-directed fractionation. The structure of 1 has been elucidated by means of 1H and 13C NMR spectroscopic studies, including 1H-13C heteronuclear correlation (HETCOR), a long-range correlation spectrum with inverse detection (HMBC) and ROESY experiments. Compound 1 showed antibiotic activity against Gram-positive bacteria and modest cytotoxic activity against HeLa, Hep-2 and Vero cell lines. Fluoride derivatives 2-4 were prepared and assayed for bioactivity, where 2 showed slight improvement of the cytotoxic potency.

Xanthine oxidase inhibitory activity of some Panamanian plants from Celastraceae and Lamiaceae.

Thirty four crude extracts of Panamanian plants, from nine species of Celastraceae and Lamiaceae, were assayed for xanthine oxidase (XO) inhibitory activity. The enzymatic activity was estimated by measuring the increase in absorbance at 290 nm due to uric acid formation. Eighty five percent of the crude extracts were found to possess XO inhibitory activity at 50 micrograms/ml and all the extracts of the species from Lamiaceae were active even at 1 micrograms/ml. The ethanol extracts of Hyptis obtusiflora Presl ex Benth. (Lamiaceae) and H. lantanaefolia Poit. (Lamiaceae) exhibited the highest activity with an inhibition of approximately 40% at 1 micrograms/ml.

Biological activity of secondary metabolites from Bupleurum salicifolium (Umbelliferae).

Secondary metabolites from Bupleurum salicifolium were tested against viruses, Gram-positive and Gram-negative bacteria, the yeast Candida albicans, the nematodes Globodera pallida and G. rostochiensis, the insect Spodoptera littoralis and the crustacean Artemia salina. These compounds were also tested against tumoral and non-tumoral cell lines. The polyacetylene 8S-heptadeca-2(Z)-9(Z)-diene-4,6-diyne-1,8-diol exhibited toxicity for A. salina and specific antibiotic activity against Gram-positive bacteria. Nine of the lignans and one coumarin showed toxicity for A. salina, and the lignans bursehernin and matairesinol inhibited the hatching of the two nematode species. These are the first lignans that have been reported as affecting phytoparasitic nematodes, and the first natural products known to have an effect on the hatching of G. pallida. Lignans may play a role in the defence mechanisms of potato plants, as allelopathic substances acting against cyst-forming nematodes.

Screening of antimicrobial and cytotoxic activities of Panamanian plants.

34 crude extracts of Panamanian plants, representing 4 species of Celastraceae and 5 species of Lamiaceae, have been screened for antimicrobial activity against thirteen bacterial strains and two yeasts. The cytotoxic activity was assayed against HeLa and Hep-2 cell lines. Fifty-three percent were found to have significant antimicrobial activity against at least two of the organisms tested, and 26.5 percent showed an IC(50) < 100 µg/ml against one cell line.

New sesquiterpenes fromMaytenus species (Celastraceae). Taxonomic and chemotaxonomic considerations concerning chileanMaytenus.

Three new dihydro-ß-agarofuran sesquiterpenes from two species ofMaytenus were isolated and their structures were elucidated by means of(1)H and(13)C NMR studies. The differences and similarities noted in the chemical content of the dihydro-ß-agarofuran sesquiterpenes from the fourMaytenus species from Chile are in line with the taxonomic characterization of these species; their geographical distribution is also given.

Biological study of triterpenequinones from celastraceae.

The cytostatic activity of several triterpenequinone methides isolated from Rzedowskia tolantonguensis and Maytenus horrida (Celastraceae) was evaluated against HeLa cell cultures. Their ID50 were determined and compared with those of other related compounds. A preliminary study of the antibacterial activity of the above triterpenequinone methides was also carried out.