RESUMO
The methanol extract of sub-aerial parts of Hieracium murorum L. gave germacra-7 alpha H-1(10)E,4Z,11 (13)-trien-12,8 alpha-olide-15-oic acid (15-->1)-beta-D-glucopyranosyl ester (1), a new sesquiterpenoid of the germacrane-type, and two new 4-hydroxybenzyl alcohol derivatives, 4-hydroxy-cinnamomic acid 4-beta-D-glucopyranosyloxybenzyl ester (2) and 3-hydroxy-2-[(4-hydroxy-phenyl)-acetoxy]-3-methyl-butyric 4-beta-D-glucopyranosyloxybenzyl ester (3). The methanol extract of sub-aerial parts of Crepis bocconi P. D. Sell gave 4-hydroxybenzoic acid 4-beta-D-glucopyranosyloxybenzyl ester (4), another new 4-hydroxybenzyl alcohol derivative. The structures of these compounds were established by means of MS and one- and two dimensional-NMR experiments.
Assuntos
Asteraceae/química , Álcoois Benzílicos/análise , Hidroxibenzoatos/química , Sesquiterpenos de Germacrano , Sesquiterpenos/análise , Álcoois Benzílicos/química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Estrutura Molecular , Sesquiterpenos/químicaRESUMO
A re-investigation of subaerial parts of Leontodon cichoraceus (Ten.) Sanguin. yielded the new germacrane-type sesquiterpenoid 15-beta-D-glucopyranosyl-8-[p-(beta-D-glucopyranosyloxy)phenylacetyl]-salonitenolide. The structure was established by APCI mass spectrometry and 1D- and 2D-NMR spectroscopy. A survey by HPLC-DAD and HPLC-MS gave no signs of this compound in 23 other taxa of Leontodon.
Assuntos
Anti-Infecciosos/isolamento & purificação , Asteraceae/química , Sesquiterpenos de Germacrano , Sesquiterpenos/isolamento & purificação , Anti-Infecciosos/química , Cromatografia Líquida de Alta Pressão , Glicosídeos/química , Glicosídeos/isolamento & purificação , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Modelos Moleculares , Conformação Molecular , Sesquiterpenos/químicaRESUMO
Some sesquiterpene lactones were recently demonstrated to inhibit inducible nitric oxide synthase (iNOS)-dependent nitric oxide (NO) synthesis. The primary objective of the present study was, therefore, to find evidence for structural requirements of sesquiterpene lactones regarding their capability to inhibit iNOS-dependent NO synthesis. Sesquiterpene lactones 1-11 were examined for their influence on nitrite accumulation in cell culture supernatants of LPS-induced RAW 264.7 macrophages. Except the taraxinic acid beta-D-glucopyranosylester 8 all compounds showed a dose-dependent inhibition of nitrite accumulation in cell culture supernatants with IC50 values ranging from 0.5 to 36.8 microM. High activity seemed to be dependent on an alpha-methylene-gammalactone functionality. Cytotoxicity and the ability to inhibit activation of transcription factor NF-kappaB are further biological activities of sesquiterpene lactones. The second point of interest was, therefore, whether the structural requirements of sesquiterpene lactones for these activities may differ or be the same for those needed to inhibit iNOS-dependent NO synthesis. Using concentrations of 1-11 required to inhibit NO synthesis cell viability was determined and NF-kappaB binding activity was measured by gel-shift experiments. Interestingly, compounds almost equally effective in inhibiting nitrite accumulation did not show the same cytotoxic potential, and most sesquiterpene lactones inhibited nitrite accumulation at concentrations where inhibition of NF-kappaB activation was not significant. These results suggest that different biological activities of sesquiterpene lactones have different structural requirements.
Assuntos
Lactonas/química , Lactonas/farmacologia , Óxido Nítrico/biossíntese , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Lactonas/síntese química , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II , Nitritos/metabolismo , Sesquiterpenos/síntese química , Relação Estrutura-AtividadeRESUMO
The methanolic extract of subaerial parts of Leontodon autumnalis afforded four new and two known sesquiterpenoids of the guaiane type. The known compounds were identified by means of (1)H and (13)C NMR spectroscopy as crepidiaside A (1) and B (2). The structures of the new compounds were determined by extensive 1D and 2D NMR experiments as 15-glucopyranosyloxy-2-oxo-guaia-3,11(13)-dien-1alp ha,5alpha, 6beta,7alpha,10alphaH-12,6-olide (3); 15-glucopyranosyloxy-2-oxo-guai-3-en-1alpha,5alpha+ ++,6beta,7alpha, 10alpha,11betaH-12,6-olide (4); 15-hydroxy-2-oxo-guai-3-en-1alpha, 5alpha,6beta,7alpha,10alpha,11betaH-12,6-+ ++olide (5); and 15-glucopyranosyloxy-2-oxo-guaia-3,11(13)-dien-1bet a,5alpha,6beta, 7alpha,10alphaH-12,6-olide (6), respectively. HPLC-DAD and HPLC-MS analyses of crude extracts of subaerial parts of 25 different taxa of the genus Leontodon revealed that compounds 1 and 2 occur in all investigated members of the section Oporinia (L. autumnalis, L. croceus, L. helveticus, L. montaniformis, L. montanus, L. pyrenaicus, and L. rilaensis) and in L. duboisii from the section Kalbfussia. Compounds 1-6 are detectable neither in other investigated taxa of Kalbfussia (L. cichoraceus, L. muelleri, and L. palisae) nor in any members of the subgenus Leontodon. Compounds 3-5 occur in high amounts only in L. croceus and L. pyrenaicus and in samples of L. autumnalis from northwestern Europe. In other members of the section Oporinia, in L. duboisii as well as in samples of L. autumnalis from the Pyrenees, the Alps, the Carpathians, and southern Central Europe, these substances occur only in trace amounts; in L. montanus and its closest relatives, compounds 3-5 are not detectable at all. Compound 6 is only detectable in samples of L. autumnalis, L. helveticus, L. pyrenaicus, L. rilaensis, and L. duboisii.
