Synthesis, Crystal Structure and Biological Activity Screening of Novel N-(α-Bromoacyl)-α-amino Esters Containing Valyl Moiety.

Three novel N-(α-bromoacyl)-α-amino esters: methyl 2-(2-bromo-3-methylbutanamido)pentanoate (1), methyl 2-(2-bromo-3-methylbutanamido)-2-phenylacetate (2) and methyl 2-(2-bromo-3-methylbutanamido)-3-phenylpropanoate (3) were synthesized. Single crystal X-ray diffraction data are reported for compounds 1 and 2. The cytotoxicity, antiinflammatory and antibacterial activity of compounds 1-3 were investigated. Additionally, the physico-chemical properties of studied compounds were calculated and an in silico toxicological study of compounds 1-3 was performed. The low level of cytotoxicity and absence of antibacterial and anti-inflammatory activity of 1-3 in tested concentrations might be a beneficial prerequisite for their incorporation in prodrugs.

Composition and antimicrobial activity of Achillea distans essential oil.

The essential oil of Achillea distans W. et K. flower heads was analyzed by GC and GC-MS. Altogether 43 components in concentrations more than 0.1% were identified representing 93.5% of the oil composition. The main constituents were 1,8-cineole (16.8%), trans-thujone (9.8%), sabinene (8.2%), borneol (7.5%), beta-pinene (6.5%), and camphor (5.8%). The oil showed moderate activity against Staphylococcus aureus and Candida albicans, and weak activity against Salmonella typhimurium, Proteus vulgaris, and Escherichia coli.

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.

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.

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.

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.

Chemotypes in Achillea collina based on sesquiterpene lactone profile.

The lactone profile of six origins of Achillea collina growing in Bulgaria was studied and significant variability was observed. The reasons for the differences in the lactone composition are discussed. Twenty-five components in total were isolated and identified, while the presence of ten lactones was proved by intensive TLC analysis in comparison with reference compounds. The structures of the components 17, 20, 25-30 were established by spectroscopic methods. The structure of 7, a cyclization product of 6, was also discussed. The anti-inflammatory activity of some extracts, fractions and individual compounds was tested in vitro by determining the inhibitory effects on induced human neutrophils.

Sesquiterpene lactones from Achillea collina J. Becker ex Reichenb.

The flower heads of Achillea collina afforded 31 individual sesquiterpene lactones, among which nine guaianolides (1, 16, 20, 21, 23, 27-30), a germacranolide (18) and a dimeric guaianolide (31) were found to be new natural products. The lactones 2-4, 12, 14, 15, 17, 19 and 25 were isolated for the first time from the investigated species. Their structures were established by spectral methods.

Oxygenated bisabolane fucosides from Carthamus lanatus L.

The aerial parts of Carthamus lanatus (Asteraceae) afforded four new oxygenated bisabolane fucosides, 10-hydroperoxy-bisabola-2,11-diene 7-O-beta-D-fucopyranoside, 11-hydro-peroxy-bisabola-2,9-diene 7-O-beta-D-fucopyranoside, 10-hydroxy-bisabola-2,11-diene 7-O-beta-D-fucopyranoside and 11-hydroxy-bisabola-2,9-diene 7-O-beta-D-fucopyranoside together with the known compounds a-bisabolol beta-D-fucopyranoside, asperuloside, sitosterol 3-O-beta-D-glucoside and stigmasterol 3-O-beta-D-glucoside. Asperuloside appears to be the second representative of the iridoid monoterpene group found in the plant family Asteraceae, which until recently was considered to lack iridoids. The main constituent a-bisabolol fucoside exhibited noticeable antibacterial and cytotoxic activities.

Bioactive phenolics from Carthamus lanatus L.

Two flavonoid aglycons, eight flavonoid glycosides, chlorogenic acid and syringin were isolated from aerial parts of Carthamus lanatus. Isorhamnetin 3-O-beta-D-glucoside and chlorogenic acid were found for the first time in the genus Carthamus and respectively, quercimeritrin, astragalin, kaempferol 3-O-beta-D-sophoroside and syringin in the species. The ethyl acetate fraction of the methanol extract exhibited a higher antioxidant activity than the butanol fraction measured by the alpha,alpha-diphenyl-beta-picrazylhydrazyl (DPPH) free radical scavenging assay. Cytotoxicity and antioxidant activities of the main constituent, luteolin 7-O-beta-D-glucoside, were evaluated.

In vitro anti-inflammatory effect of Carthamus lanatus L.

The anti-inflammatory activity of four total extracts, their fractions and two main constituents (alpha-bisabolol beta-D-fucopyranoside and luteolin 7-O-glucoside) of Carthamus lanatus L. aerial parts, were assessed in vitro by determining the inhibitory effects on induced human neutrophils. The dichloromethane extract and its water-alcoholic part exhibited the most significant inhibitory effects.

Clastogenic effect of Carthamus lanatus L. (Asteraceae).

The clastogenic effect of total dichloromethane, methanol and water extracts, four bioactive fractions and three individual constituents from Carthamus lanatus aerial parts were evaluated in mice by bone marrow chromosome aberration assay with mitomycin C as positive control. Significant differences in the percentage of aberrant mitosis of the extracts were observed. The dichloromethane extract exhibited a considerable clastogenic effect and the water extract a negligible one. Different types of chromosome aberrations and time-dependant effects for the active fractions and individual compounds were found.

Alkaloids from the roots of Senecio macedonicus Griseb.

The new alkaloids 7-,9-diangeloylplatynecine (1) and 8-episarracine N-oxide (2), were isolated and identified from the roots of Senecio macedonicus. Another one, 8-epineosarracine was detected by GC/MS analyses of the crude alkaloid mixture. The cytotoxicity and biological activity of the alkaloids were tested on normal murine spleen lymphocytes and P3U1 mouse myeloma.

Alkaloids from Senecio aquaticus.

Erucifoline (1) and 9-angeloylhastanecine (2) were isolated from the aerial parts of Senecio aquaticus. Five other pyrrolizidine alkaloids were tentatively identified by GC/MS analysis: jacobine; seneciphylline; spartioidine; jacozine; and senecionine.