Root constituents of Cichorium pumilum and rearrangements of some lactucin-like guaianolides

Two eudesmanolides, eight lactucin-like guaianolides and five phenolic compounds were isolated for the first time from roots of Cichorium pumilum, along with two previously reported eudesmane-type sesquiterpene lactones. Rearrangements of some lactucin-like guaianolides during isolation procedures were also discussed.     

Inhibitors of the LPS-induced NF-kappaB activation from Artemisia sylvatica

Three guaianolide sesquiterpene lactones, 3alpha,4alpha-epoxyrupicolins C-E, together with six known sesquiterpenes, artemisolide, 3-methoxytanapartholide, deacetyllaurenobiolide, moxartenolide as well as arteminolides B and D were isolated by bioassay-guided fractionation from the methanol extract of the aerial parts of Artemisia sylvatica using the NF-kappaB mediated reporter gene assay. All isolated compounds displayed inhibitory activity on the LPS-induced NF-kappaB activation, NO production, and TNF-alpha production with IC50 values of 0.49-7.17, 1.46-6.16, and 3.19-27.76 microM, respectively, in RAW264.7 cells. It was also established that arteminolide B suppressed the expression of NF-kappaB target genes such as iNOS and COX-2. This is the first report of NF-kappaB inhibitory activities of these compounds and supports the pharmacological use of Artemisia sylvatica, which has been employed as an herbal medicine for the treatment of inflammation.     

Dehydrocostuslactone and plant growth activity of derived guaianolides

The stereostructures of two new guaianolides, isodehydrocostuslactone and isozaluzanin C, isolated previously from Saussurea lappa, have been confirmed by their correlation with dehydrocostuslactone. Twenty new derivatives have been synthesized from these guaianolides and these have been tested as plant growth regulators. The conjugated lactones which have an exocyclic methylene group at C-4 conjugated with a C-3 ketone, show distinct enhancement in their root-forming potential, as compared with their 3-deoxy derivatives. Of further significance is the fact that these ketones display maximum activity only at lower concentrations. Other compounds show the expected structure-biological activity relationships displayed in general by guaianolides. However, the presence of an epoxide at the C-3, C-4 position does not affect the biological activity, which is indeed the case when the epoxide group occupies the C-4, C-14 position in guaianolides. The major biological parameter studied was rooting in-stem cuttings of Phaseolus aureus.     

New germacranolides,guaianolides and rearranged Guaianolides from Lasiolaena santosii

The aerial parts of L. santosii afforded three new diterpenes, a phenylpropanol, three eudesmane derivatives, three germacranolides, seventeen guaianolides and four rearranged guaianolides of a, so far, unknown type. Furthermore, several known compounds were isolated. The structures of the new compounds, the separations of which caused difficulties, were elucidated by spectroscopic methods and by some chemical transformations. The chemotaxonomic situation is discussed briefly.     

Further guaianolides and 5-alkylcoumarins from gutenbergia and bothriocline species

From Gutenbergia marginata ten new guaianolides were isolated. Two guaianolides isolated previously from Erlangea inyangana are identical with two further lactones and their structures have been revised. From Bothriocline ripensis ethulia coumarin and two further 5-alkylcoumarin derivatives, one being a chromone, were isolated, while B. longipes and B. eupatorioides gave nine 5-alkylcoumarins and two related compounds. The structures were elucidated by highfield NMR techniques and a few chemical transformations.     

Dimeric guaianolides from Artemisia sieversiana

The aerial parts of Artemisia sieversiana afforded in addition to known compounds five new guaianolides and four dimeric guaianolides, three of them closely related to absinthin and one derived from estafiatin as a monomer. The structures were elucidated by extensive NMR studies, which allowed the assignment of the 14 chiral centres. Artemisia frigida afforded several known compounds and one new guaianolide, 8-desoxy-cumambrin B, the most likely precursor of many guaianolides.     

Sesquiterpenoids and phenolics from Crepis conyzifolia

From the roots of Crepis conyzifolia, two new and two known guaianolides were isolated together with three known phenylpropanoids. Structures of the new compounds were established as 8beta-hydroxy-4beta, 15-dihydrozaluzanin C and 4beta, 15, 11beta, 13-tetrahydrozaluzanin C-3-O-beta-glucopyranoside by spectral methods. The identity of 8-epiisolippidiol and dentalactone was also discussed.     

Lignans from Saururus chinensis inhibiting the transcription factor NF-kappaB

The sesquineolignans, saucerneol D and saucerneol E were isolated from the roots of Saururus chinensis together with four known lignans, manassantin A, manassantin B, (-)-saucerneol methyl ether, and (+)-saucernetin. Structure elucidation was based on the analysis of spectroscopic data and anti-inflammatory activity was studied using HeLa cells transfected with NF-kappaB reporter construct. All compounds except for (+)-saucernetin inhibited NF-kappaB dependent reporter gene expression with IC50 values of 2.5-16.9 microM.     

Highly oxygenated guaianolides from Bishopanthus soliceps

In addition to known compounds several highly oxygenated guaianolides and eudesmanolides, derived from 1β-hydroxyarbusculin A, were isolated from the aerial parts of Bishopanthus soliceps, a member of a new genus of the tribe Liabeae.     

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.     

Guaianolides in apiaceae: perspectives on pharmacology and biosynthesis

The guaianolide group of sesquiterpene lactones contains a large number of compounds with biological activity. One of these guaianolides, thapsigargin from the genus Thapsia (Apiaceae), has been a subject of particular interest in recent years because of its ability to induce apoptosis, as the active part of a pro-drug, has produced promising results for the targeted treatment of prostate cancer. In this review, recent advances in understanding the biosynthetic pathway of sesquiterpenes in plants is described with a special emphasis on guaianolides, and a hypothetical pathway for the biosynthesis of thapsigargin is presented. Eighty-seven guaianolides from Apiaceae are presented. These compounds provide clues to possible enzymatic mechanisms generating the guaianolides in Apiaceae. Some of these 87 compounds have proven or might prove interesting with regards to their biological activity.     

Sesquiterpene lactones from the leaves of Hedyosmum brasiliense (Chloranthaceae)

Hedyosmum brasiliense Miq. is an endemic aromatic arborescent shrub that is the only representative of the Chloranthaceae in Brazil. There have been few studies seeking to determine its chemical constituents and/or pharmacological effects. This work describes the isolation and identification of sesquiterpene lactones from the leaves, including guaianolides, elemanolides and a lindenanolide. These were tested against Mycobacterium tuberculosis, together with podoandin, onoseriolide and some other common phenolics. The structures of the isolated compounds were determined based on extensive analysis of 1D and 2D NMR spectroscopic and MS data, as well as comparison with published data. The compounds found were the guaianolides, 1,2-epoxy-10α-hydroxy-podoandin and 1-hydroxy-10,15-methylenepodoandin, the elemenolide 15-acetoxy-isogermafurenolide and the lindenanolide 8α/β,9α-hydroxy-onoseriolide, along with the previously isolated guaianolide podoandin, the lindenanolide onoseriolide and the elemenolide 15-hydroxy-isogermafurenolide. The phenolic compounds isolated were scopoletin, vanillin, vanillic acid, protocatechuic aldehyde and ethyl caffeate. The isolated sesquiterpene lactones did not show anti-mycobacterial activity against isoniazid-sensitive M. tuberculosis cultures at concentrations of 1–30 μM.     

A new guaianolide glucoside from aerial parts of Lactuca aculeata

From aerial parts of Lactuca aculeata one new and ten known sesquiterpene lactone aglycones and glycosides were isolated, including four lactucin-type guaianolides, six costus lactone-type guaianolides and one melampolide-type germacranolide. The structure of the new compound was determined as 11β-hydroxycrepidiaside B by high resolution mass spectrometry and 1D- and 2D-NMR spectroscopy.     

Six guaianolides from Stylotrichium rotundifolium

The investigation of Stylotrichium rotundifolium afforded the epoxide of β-sesquiphellandrene, a new derivative of geranylnerol and six guaianolides not isolated previously. Furthermore, two germacranolides also present in a Lasiolaena species and several known compounds were isolated. The structures were elucidated by detailed ¹H NMR investigations. The chemotaxonomic situation is discussed briefly.     

Neue elemanolide und guajanolide aus Zinnia-arten

The investigation of three Zinnia species afforded thirteen new elemanolides. Though these compounds could be separated only in part, the spectroscopic data clearly indicate the proposed structures. Furthermore, four new guaianolides were isolated. The chemotaxonomic situation is discussed briefly.     

Cytotoxic constituents of Achillea clavennae from Montenegro

Examination of the aerial parts of Achillea clavennae afforded eight guaianolides (1-8), three bisabolenes (9-11), four flavonols (12-15), sesamin (lignan) and isofraxidin (coumarin). The structures of the new compounds (2, 4, 5, 7 and 10) were determined by spectroscopic methods. The antiproliferative action of 2, 8, 9 and 12 were tested to HeLa, K562 and Fem-X human cancer cell lines. Guaianolides 2 (9alpha-acetoxyartecanin) and 8 (apressin) showed significant cytotoxic effects to all tested lines and inducumenone (9) exhibited a moderate activity. The most active was flavonol centaureidin (12), already known as cytotoxic compound.     

Neue guaianolide aus Cacosmia rugosa

The roots of C. rugosa afforded, in addition to known compounds, a C₁₇-acetylenic epoxide and five new guaianolides, four of them being hydroperoxides. The structures were elucidated by extensive NMR studies. The aerial parts only contain triterpene mixtures, as those of C. hieronymi. The compounds isolated confirm that Cacosmia is unrelated chemically to true members of the tribe Senecioneae.     

The first sesquiterpene lactones esterified with a sesquiterpenic acid

From Hypochoeris glabra two guaianolides esterified with an unusual sesquiterpenic acid were isolated. Proton-catalysed rearrangement of the cyclopropane derivative led to a phenolic acid. The structures were elucidated by high-field ¹H NMR spectroscopy. Further guaianolides were isolated from H. uniflora and Lactuca floridana. These structures were elucidated by spectroscopic methods. The chemotaxonomic situation in the tribe is discussed briefly.     

Pseudoguaianolides carabrone derivatives from Loxothysanus sinuatus

The aerial parts of Loxothysanus sinuatus afforded in addition to known compounds nine new pseudoguaianolides, three guaianolides and five carabrone derivatives. The structures were elucidated by spectroscopic methods. The chemotaxonomy is discussed briefly. The configurations of two guaianolides were corrected.     

Rupicolin-A and -B,rupin-A and -B,and cumambrin-B oxide from Artemisia tripartita ssp. Rupicola

Five new sesquiterpene Iactones have been isolated from Artemisia tripartita Rydb. ssp. rupicola Beetle. The compounds, all guaianolides, are structurally related in what appears to be a sequence in which epoxidation plays the principal role.