Antimalarial sesquiterpene lactones from Distephanus angulifolius

Combined use of bioassay-guided fractionation based on in vitro antiplasmodial assay and dereplication based on HPLC-PDA-MS-SPE-NMR led to isolation of (6S,7R,8S)-14-acetoxy-8-[2-hydroxymethylacrylat]-15-helianga-1(10),4,11(13)-trien-15-al-6,12-olid and (5R,6R,7R,8S,10S)-14-acetoxy-8-[2-hydroxymethylacrylat]-elema-1,3,11(13)-trien-15-al-6,12-olid, along with vernodalol, vernodalin, and 11,13β-dihydroxyvernodalin from extract of Distephanus angulifolius. All compounds were identified by spectroscopic methods, including 1D and 2D homo- and heteronuclear NMR experiments. The isolated compounds showed IC₅₀ values in the range 1.6-3.8 μM and 2.1-4.9 μM against chloroquine sensitive D10 and chloroquine resistant W2 Plasmodium falciparum strains, respectively.     

New sesquiterpene lactones from Inula oculus-christi L.

Investigation of the aerial parts of Inula oculus-christi L. led to the identification of four new sesquiterpene lactones: an eudesmanolide (4α,15α-epoxypulchellin E) and three guaianolides (2α-acetoxy-4α,9β-dihydroxy-1β-guaia-11(13),10(14)-dien-12,8α-olide, 9β,10β-epoxygaillardin, 9α,10α-epoxy-2-epi-gaillardin), in addition to the known gaillardin, pulchellin E, pulchellin C and 3-O-palmitates of 16β-hydroxylupeol, 16β-hydroxy-β-amyrin, and faradiol. The structures of all compounds have been elucidated on the basis of their spectral data.     

Antiproliferative and apoptotic sesquiterpene lactones from Carpesium faberi

Four new (1-4) and 13 known (5-17) sesquiterpene lactones along with two known diterpenes (18, 19) were isolated from the whole plant of Carpesium faberi. The new structures were elucidated by means of spectroscopic techniques and some chemical transformations to be pseudoguaian-1α(H)-8α,12-olide-4β-O-β-d-glucopyranoside (1), 4β,10α-dihydroxy-5α(H)-1,11(13)-guaidien-8α,12-olide (2), 4β,10β-dihydroxy-5α(H)-1, 11(13)-guaidien-8β,12-olide (3), and (4S)-acetyloxyl-11(13)-carabren-8β,12-olide (4). All isolates were tested against MCF-7 human breast cancer cells using the MTT assay. Among them, the sesquiterpene lactones (except tomentosin 17) possessing an α-methylene-γ-lactone moiety were found to have in vitro antiproliferative activities, with IC₅₀ values of 3.0-38.8 μg/mL. The effects of four selected sesquiterpene lactones (guaianolide 2, carabranolide 4, pseudoguaianolide 9, eudesmanolide 13) on the cell cycle were examined using flow cytometry (FCM).     

Ent-kaurane glycosides and sesquiterpene lactones of the hirsutinolide type from Vernonia triflosculosa

Investigation of the aerial parts of Vernonia triflosculosa afforded three hirsutinolides of which 8alpha-(4alpha-hydroxymethacryloyloxy)-10alpha-hydroxy-1,13-dimethoxy-hirsutinolide is new, three ent-kaurane diterpenes, among which the 19-[alpha-L-arabinopyranosyl-(1-->2)-beta-D-glucopyranosyl] esters of 16beta-hydroxy-ent-kauran-19-oic acid and of 16beta,17-hydroxy-ent-kauran-19-oic acid are also new. Diterpenes are reported here for the first time in the large genus Vernonia. Their structures were elucidated using 1D and 2D NMR measurement as well as ESI, CIMS, and HRMS analysis. Two hirsutinolides were studied for their NF-kappaB DNA binding activity in HaCaT cells (a human cell line similar to keratinocytes) and for their inhibition on IL-8 production in HeLa cells.     

Systematic implications of sesquiterpene lactones in Lactuca species

A chemosystematic study of eleven species from the genus Lactuca (Asteraceae) was performed, based on the distributional data for eight sesquiterpene lactones as diagnostic characters. The lactones were identified in leaf and root extracts by comparison of their HPLC retention times and on-line UV spectra with those of reference compounds. Our results support the status of the section Lactuca, subsection Lactuca as a recognizable group within the genus, although Lactuca aculeata is a distinct species. Moreover, sesquiterpene lactone patterns of Lactuca perennis, Lactuca tatarica, Lactuca indica and Lactuca capensis are also given. It is worth noting that the sesquiterpene lactones are absent from Lactuca tenerrima. The chemosystematic impact of lactucin-type guaianolides and the germacranolide lactuside A is discussed briefly.     

Allelopathic potential of two sesquiterpene lactones from Magnolia grandiflora L.

The allelopathic effects of the two sesquiterpene lactones, costunolide and parthenolide, isolated from the leaves of Magnolia grandiflora L. were evaluated on the wheat (Triticum aestivum L.), lettuce (Lactuca sativa L.), radish (Raphanus sativus L.) and onion (Allium cepa L.). Seed germination of the test species was significantly reduced at 500 μg/ml by both compounds. Both sesquiterpenes showed pronounced inhibition of root length of the test species and the inhibitory effect was concentration-dependent. In addition, shoot growth of the four species was significantly inhibited at all the concentrations tested (10–500 μg/ml). Parthenolide reduced germination and inhibited seedling growth more than costunolide. Inhibition of root growth was generally greater than that of shoot growth. The results encourage the use of these sesquiterpenes as models for development of new herbicides.     

Antifeedant properties and chemotaxonomic implications of sesquiterpene lactones and syringin from Rhaponticum pulchrum

From aerial parts of Rhaponticum pulchrum the guaiane-type sesquiterpene lactones aguerin B, janerin, 19-deoxyjanerin, chlorojanerin, 15-dechloro-15-hydroxychlorojanerin, cynaropicrin, cebellin G, repdiolide and repensolide were isolated, together with the phenylpropanoid glucoside syringin. In no-choice and two-choice feeding experiments aguerin B, chlorojanerin and syringin were shown to be good antifeedants against the three species of the stored product insect pests Sitophilus granarius, Trogoderma granarium and Tribolium confusum, while janerin and cynaropicrin inhibited feeding of the latter species. However, the highest antifeedant activity was recorded for the extract of the plant enriched in sesquiterpene lactones. The unexpected finding was that syringin inhibited feeding of the insects.     

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.     

Sesquiterpene lactones and other constituents from Matricaria chamomilla L.

An ethanolic extract of the aerial parts of Matricaria Chamomilla L. collected at Oued Tonga near El-Kala is eastern Argelia yielded two new substances named matricolone and chamolol, together with four known compounds. The structure of the new compounds were determined by chemical transformations and NMR spectroscopy with ¹H-¹H (COSY and ROESY), ¹H-¹³C (one bond and long range correlations) two dimensional experiments. The results obtained indicate the presence of sesquiterpene lactones of the eudesmanolide, germacranolide and guaianolide types. These products can be considered to be of great interest from a chemotaxonomical point of view for this wild-growing plant, because these types of lactones have not been found together in other Matricaria species.     

Sesquiterpene lactones from the aerial parts of Anthemis arvensis L.

Two known sesquiterpene lactones, antheindurolides A and B, together with five new related lactones with the same unusual skeleton were isolated from the aerial parts of Anthemis arvensis growing in Serbia. The originally proposed structure of antheindurolide B was revised. This (antheindurolide) type of lactones, detected so far only in the genus Anthemis (Anthemis indurata, Anthemis pseudocotula and Anthemis cotula) could be of chemotaxonomic significance.     

Antimicrobial activities of sesquiterpene lactones and inositol derivatives from Hymenoxys robusta

Six compounds from the aerial parts of the Argentinean plant Hymenoxys robusta (Rusby) Parker were isolated and their structures elucidated using extensive spectroscopic analyses. These compounds comprise two inositol derivatives and four 3,4-seco-pseudoguaianolides, including vermeerin. Bioactivity assays of these compounds against bacterial and fungal pathogens showed that only vermeerin possessed antimicrobial activity specific against Staphylococcusaureus, and showed no toxicity when exposed to human-derived macrophages.     

Sesquiterpene lactones from the endemic Cape Verdean Artemisia gorgonum

Leaves and flowers of Artemisia gorgonum (Asteraceae) collected in Fogo, Cape Verde islands, were phytochemically investigated and resulted in isolation and characterization of three guaianolides 1, 2, 5, and a secoguainolide 4, in addition to eight known guaianolides 6-11 and two known germacranolides 12, 13. Structures were elucidated by 1D and 2D NMR experiments. Careful examination of the ¹³C NMR spectrum led to revision of the structure of a previously described guaianolide from 2 to 3. Most compounds exhibited mild antiplasmodial activities, ridentin (13) being the most interesting with an IC₅₀ of 3.8 ± 0.7 μg ml⁻¹ against Plasmodium falciparum FcB1 and weak cytotoxicity in a vero cell line (IC₅₀ 71.0 ± 3.9 μg ml⁻¹).     

Sesquiterpene lactones as chemotaxonomic markers in genus Anthemis

Sesquiterpene lactones isolated from the genus Anthemis are used as chemotaxonomic markers. The obtained results support with some exceptions the botanical classification in Flora Europaea. Discrepancy between the lactone profile, cluster analysis and classification of A. melampodina, A. macedonica and A. austriaca in the genus Anthemis is discussed. The lactone composition of the undescribed as an European species A. plutonia correlates well with the guaianolide containing group of sect. Hiorthia.     

Antileishmanial activity and ultrastructural changes of sesquiterpene lactones isolated from Calea pinnatifida (Asteraceae)

Bioactivity-guided fractionation of antileishmanial active CH₂Cl₂ phase of MeOH extract from leaves of Calea pinnatifida led to isolation of two sesquiterpene lactones calein C (1) and calealactone C (2), which structures were stablished on the basis of spectroscopic analysis. Compounds 1 and 2 displayed potent activity against Leishmania amazonensis promastigotes with EC₅₀ of 1.7 and 4.6 µg mL⁻¹, respectively. Compound 2 presented low cytotoxicity for J774 macrophages and displayed activity against amastigote forms of L. amazonensis similar to miltefosine with CC₅₀ values of 31.73 and 27.18 µg mL⁻¹, respectively. Additionally, compounds 1 and 2 caused ultrastructural changes in promastigotes leading to a loss of their classical structural morphology, as evidenced by electron microscopy. Also compound 2 decreased the mitochondria membrane potential. To the best of our knowledge, this is the first occurrence of 1 and 2 in C. pinnatifida. The results obtained highlighted the importance of studying sesquiterpene lactones isolated from Calea pinnatifida in terms of antileishmanial activity, in order to understand the mechanism of action of the isolated compounds in promastigotes forms of L. amazonensis.     

Sesquiterpene lactones and other constituents from Stevia jorullensis

A chemical study of the aerial parts of Stevia jorullensis was carried out as a contribution to the knowledge of the chemistry of the genus Stevia. In this investigation the sesquiterpene lactones 11β,13-dihydrocostunolide (1), 11,13-dihydroreynosin (4), and 1β-hydroxycolartin (5) were isolated for the first time in the genus. Additionally, chlorogenic acid (8), the steroidal compounds β-sitosterol (2), stigmasterol (3), β-sitosteryl glucopyranoside (6), and stigmasteryl glucopyranoside (7) were also isolated. This is the third report of the presence of a 11,13-dihydrogermacranolide and the second of 11,13-dihydroeudesmanolides in the genus Stevia.