Steroidal alkaloids of Veratrum lobelianum Bernh. and Veratrum nigrum L.

Twelve steroidal alkaloids were isolated from four populations of Veratrum lobelianum Bernh. and Veratrum nigrum L. Full NMR data for veralosinine (1), and extensive 1H NMR data for veralosine (3) and teinemine (5) are presented here for the first time. (+/-)-15-O-(2-Methylbutyroyl)germine (10) is undescribed up to now. The antiproliferative activities of veranigrine, veralosinine, and neogermitrine have shown that they are a perspective for further studies.

Screening of some saponins and phenolic components of Tribulus terrestris and Smilax excelsa as MDR modulators.

BACKGROUND: Cytotoxic activity of saponins and phenolic compounds have been described in the literature, but no reports were found on their multidrug resistance (MDR)-modulating effects on human mdr1 gene-transfected mouse lymphoma cell line. MATERIALS AND METHODS: Methylprototribestin, structurally related compounds and a mixture of 3 acetylated isomers of methylprotodioscin were investigated for antiproliferative effect and modulation of drug accumulation. RESULTS: The growth inhibitory dose (ID50) of the compounds ranged from 12.64 to 20.62 mug/ml. Methylprototribestin was the most effective resistance modifier. However, methylprotodioscin, pseudoprotodioscin, prosapogenin A of dioscin, tribestin and 5-O-caffeoylshikimic acid showed moderate MDR reversal activity. In a checkerboard method, methyloprototribestin and the mixture of the 3 acetylated isomers enhanced the antiproliferative effects on MDR cells in combination with doxorubicin. CONCLUSION: Based on these results, methylprototribestin and the mixture of the 3 acetylated isomers can be recommended for further in vivo experiments in combination with anthracyclines in human MDR-cancer xenograft transplanted mice.

MDR-reversal activity of chalcones.

The ability of 11 chalcones with 3,4,5-trimethoxy substitution on ring A to inhibit the transport activity of P-glycoprotein was studied. Flow cytometry was applied in multidrug-resistant human mdr1 gene-transfected mouse lymphoma cells (L 5178 Y). The reversal of multidrug resistance (MDR) was investigated by measuring the accumulation of rhodamine-123 in cancer cells. Verapamil was applied as a positive control. The majority of the tested compounds were proved to be effective inhibitors of the outward transport of rhodamine-123. In the MTT test, chalcones 2, 3, 5 and 7 exhibited the strongest antiproliferative effects, with 50% inhibitory dose (ID50) =0.19, 0.19, 0.29 and 0.14 microg/mL, respectively. The least effective compounds were 1, 4, 8 and 11, with ID50 values in the range of 1.5-3.5 microg/mL. The antiproliferative effect was shown to be affected by the type of substitution at the p-position on ring B. Chalcone 7, with a p-chloro group on ring B, was the most effective in MDR reversal, causing a marked increase in drug accumulation from 0.4 to 40 microg/mL. In combination with epirubicin, compound 7 displayed synergistic properties while compound 3 exhibited an additive effect. The data presented here indicated that some calcone derivatives can be regarded as effective compounds for reversal of MDR.

Volatile components of some Rutaceae species.

The volatile components of the aerial parts of Ruta graveolens and Haplophyllum suaveolens, as well as of leaves of Zanthoxylum limoncello, Z. panamense and Z. setulosum have been studied by GC/MS analysis.

GC-mS analysis and anti-microbial activity of acidic fractions obtained from Paeonia peregrina and Paeonia tenuifolia roots.

Fourteen aromatic and 24 aliphatic acids were determined by GC-MS analysis of acidic fractions obtained from Paeonia peregrina and Paeonia tenuifolia roots. Benzoic acid and its monohydroxy-, dihydroxy- and trihydroxy-derivatives are the main acid components of both Paeonia species. Some fractions could serve as a source of benzoic, 4-hydroxybenzoic, vanillic and gallic acids, as well as of ethyl gallate. The fractions inhibited the growth of Staphylococcus aureus, Escherichia coli and Candida albicans.

Two new sulfated furostanol saponins from Tribulus terrestris.

The known furostanol saponins methylprotodioscin and protodioscin and two new sulfated saponins, sodium salt of 26-O-beta-glucopyranosyl-22alpha-methoxy-(25R)-furost-5-ene-3beta,26-diol-3-O-alpha-rhamnopyranosyl-(1-->2)-beta-4-O-sulfo-glucopyranoside (methylprototribestin) and sodium salt of 26-O-beta-glucopyranosyl-22alpha-hydroxy-(25R)-furost-5-ene-3beta,26-diol-3-O-alpha-rhamnopyranosyl-(1-->2)-beta-4-O-sulfo-glucopyranoside (prototribestin) have been isolated from the aerial parts of Tribulus terrestris L. growing in Bulgaria. The structures of the new compounds were elucidated on the basis of 1D and 2D (DQF-COSY, TOCSY, HSQC-TOCSY, HSQC, HMBC, ROESY) NMR data, ESI mass spectra and chemical transformation.

New furostanol saponins from Smilax aspera L. and their in vitro cytotoxicity.

The occurrence of the two new cis-fused A/B rings furostanol saponins (25S)-26-O-ß-D-glucopyranosyl-5ß-furostan-1ß,3ß,22α,26-tetraol-1-O-ß-D-glucopyranoside and (25S)-26-O-ß-D-glucopyranosyl-5ß-furostan-1ß,2ß,3ß,5ß,22α,26-hexaol and the known compounds (25S)-26-O-ß-D-glucopyranosyl-5ß-furostan-3ß,22α,26-triol-3-O-α-L-rhamnopyranosyl-(1 → 2)-O-ß-D-glucopyranosyl-(1 → 2)-O-ß-D-glucopyranoside and (25S)-26-O-ß-D-glucopyranosyl-5ß-furostan-3ß,22α,26-triol-3-O-ß-D-glucopyranosyl-(1 → 2)-O-ß-D-glucopyranoside, trans-resveratrol, (+) catechin and (-) epicatechin in the rhizomes of Smilax aspera is reported. All saponins have been isolated as their 22-OMe derivatives, which were further subjected to extensive spectroscopic analysis. The isolated furostanol saponins were evaluated for cytotoxic activity against human normal amniotic and human lung carcinoma cell lines using neutral red and MTT assays. In vitro experiments showed significant cytotoxicity in a dose dependent manner with IC(50) values in the range of 32.98-94.53 µM.

Alkaloids derived from genus Veratrum and Peganum of Mongolian origin as multidrug resistance inhibitors of cancer cells.

Alkaloids comprise one of the largest groups of plant secondary metabolites including vinca alkaloids. The ability of six alkaloids from Veratrum lobelianum, one from Veratrum nigrum and three from Peganum nigellastrum to modify transport activity of MDR1 was studied. Flow-cytometry in a multidrug-resistant human MDR1-gene-transfected mouse lymphoma cells (L5178Y) was applied. The inhibition of multidrug resistance was investigated by measuring the accumulation of rhodamine-123 in cancer cells. Veralosinine and veranigrine were the most effective resistance modifiers. In a checkerboard method veralosinine and veranigrine enhanced the antiproliferative effects of doxorubicin on MDR cells in combination. The structure-activity relationships were discussed.

Steroidal saponins from Smilax excelsa rhizomes.

From the n-butanol soluble fraction of the methanol extract of the rhizomes of Smilax excelsa, three new furostanol saponins 3-O-[4-O-acetyl-alpha-L-rhamnopyranosyl-(1 --> 2)-{alpha-L-rhamnopyranosyl-(1 --> 4)}-beta-D-glucopyranosyl]-26-O-[beta-D-glucopyranosyl]-22alpha-hydroxy-(25R)-furost-5-ene-3beta,26-diol (1), 3-O-[2-O-acetyl-alpha-L-rhamnopyranosyl-(1 --> 2)-{alpha-L-rhamnopyranosyl-(1 --> 4)}-beta-D-glucopyranosyl]-26-O-[beta-D-glucopyranosyl]-22alpha-hydroxy-(25R)-furost-5-ene-3beta,26-diol (2), 3-O-[3-O-acetyl-alpha-L-rhamnopyranosyl-(1 --> 2)-{alpha-L-rhamnopyranosyl-(1 --> 4)}-beta-D-glucopyranosyl]-26-O-[beta-D-glucopyranosyl]-22alpha-hydroxy-(25R)-furost-5-ene-3beta,26-diol (3), and three known saponins: protodioscin (4), pseudoprotodioscin (5) and dioscin (6) were isolated.

Chemical composition and antimicrobial activity of wild garlic Allium ursinum of Bulgarian origin.

The chemical composition of fresh flowers from Allium ursinum (ramsons, bear's garlic, wild garlic) growing in Bulgaria has been studied. Thymidine (1), adenosine (2), astragalin (kaempferol-3-O-beta-D-glucopyranoside (3), kaempferol-3-O-beta-D-glucopyranosyl-7-O-beta-D-glucopyranoside (4), kaempferol-3-O-beta-D-neohesperoside (5), and kaempferol-3-O-beta-D-neohesperoside-7-O-beta-D-glucopyranoside (6) were isolated from the n-butanol extract and identified by different spectroscopic and spectrometric methods. Thymine (7), uridine (8), uracil (9) and 5-chloro-uridine (10) were detected in the same extract by GC-MS. This is the first report of the occurrence of 1, 2, 4, 7 - 10 in the flowers of A. ursinum. GC-MS of the volatile components of fresh flowers and leaves from the same plant revealed a high content of sulfur compounds, some of which are reported for the first time for A. ursinum. The antimicrobial activities of extracts from fresh flowers and leaves of A. ursinum have been tested; some extracts exhibited moderate antifungal properties.