Chemical constituents from Saussurea licentiana Hand.-Mazz

Chemical investigation of Saussurea licentiana led to the isolation of ten compounds, and their structures were identified to be dia-aurantiamide acetate (1), (+)-pinoresinol 4-O-β-D-glucoside (2), encelin (3), apigenin (4), luteolin (5), jaceosidin (6), luteolin -7-O-β-D- glucopyranoside (7), α-amyrin (8), β-amyrin (9), taraxasterol (10) on the basis of mass and NMR spectra. This is the first report on the occurrence of compounds 1, and 2 in the genus Saussurea while 1 is reported for the first time from Asteraceae. This work also represents the first phytochemical work on the whole plants of S. licentiana.     

Cadinenes and other metabolites from Verbesina sphaerocephala A. Gray

The phytochemical study of the aerial parts of Verbesina sphaerocephala A. Gray afforded six sesquiterpene lactones of cadinene type, five of them described for the first time, along with known phenyl propanoids, terpenoids, and phenolic compounds. Structures on new compounds were elucidated by spectroscopic techniques including CD and X-ray analyses, and known compounds were identified by comparing their spectral data with those previously reported. Cadinene-like sesquiterpene lactones could be characteristic metabolites of V. sphaerocephala.     

New antifungal scaffold derived from a natural pharmacophore: Synthesis of α-methylene-γ-butyrolactone derivatives and their antifungal activity against Colletotrichum lagenarium

Thirty new and thirty-four known analogues were designed and synthesized to improve the potential use of the α-methylene-γ-butyrolactone ring, a natural pharmacophore. All structures were confirmed by ¹H and ¹³C NMR, MS, and single-crystal X-ray diffraction analyses. The results of antifungal and cytotoxic activity indicated that the synthesized analogues showed significant inhibitory activity and limited selectivity. Compound 45 exhibited the highest antifungal activity with IC₅₀ = 22.8 μM but moderate cytotoxic activity with IC₅₀ = 28.5 μM (against BGC823 cell line) and 7.7 μM (against HeLa cell line). Analysis of structure–activity relationships revealed that the incorporation of an aromatic ring into the β, γ positions of the lactone ring improved antifungal activity, and that the introduction of electron-withdrawing groups into the aromatic rings increased the activity compared with electron-donating groups. The above results identified 4-phenyl-3-phenyl-2-methylenebutyrolactone (33) as a lead scaffold for discovering and developing novel and improved crop-protection agents.     

Cynaropicrin targets the trypanothione redox system in Trypanosoma brucei

In mice cynaropicrin (CYN) potently inhibits the proliferation of Trypanosoma brucei—the causative agent of Human African Trypanosomiasis—by a so far unknown mechanism. We hypothesized that CYNs α,β-unsaturated methylene moieties act as Michael acceptors for glutathione (GSH) and trypanothione (T(SH)₂), the main low molecular mass thiols essential for unique redox metabolism of these parasites. The analysis of this putative mechanism and the effects of CYN on enzymes of the T(SH)₂ redox metabolism including trypanothione reductase, trypanothione synthetase, glutathione-S-transferase, and ornithine decarboxylase are shown. A two step extraction protocol with subsequent UPLC–MS/MS analysis was established to quantify intra-cellular CYN, T(SH)₂, GSH, as well as GS-CYN and T(S-CYN)₂ adducts in intact T. b. rhodesiense cells. Within minutes of exposure to CYN, the cellular GSH and T(SH)₂ pools were entirely depleted, and the parasites entered an apoptotic stage and died. CYN also showed inhibition of the ornithine decarboxylase similar to the positive control eflornithine. Significant interactions with the other enzymes involved in the T(SH)₂ redox metabolism were not observed. Alongside many other biological activities sesquiterpene lactones including CYN have shown antitrypanosomal effects, which have been postulated to be linked to formation of Michael adducts with cellular nucleophiles. Here the interaction of CYN with biological thiols in a cellular system in general, and with trypanosomal T(SH)₂ redox metabolism in particular, thus offering a molecular explanation for the antitrypanosomal activity is demonstrated. At the same time, the study provides a novel extraction and analysis protocol for components of the trypanosomal thiol metabolism.     

New derivatives from the aerial parts of Boerhaavia diffusa L. (Nyctaginaceae)

Boerhaavia diffusa L. is used in the traditional medicine of several Asian countries. The isolation and identification of five new compounds, together with 11 known compounds, from the ethyl acetate extract of the aerial part of B. diffusa grown Vietnam is reported. The structure of the new compounds was established by 1D and 2D NMR spectroscopy, and high resolution ESI-MS analysis. New compounds are two rotenoids: 9,11-dihydroxy-6,10-dimethoxy[1]benzopyrano[3,4-b][1]benzopyran-12(6H)-one (boeravinone P, 3) and 3-[2-(β-d-glucopyranosyloxy)-3-hydroxyphenyl]-5-hydroxy-2-hydroxymethyl-7-methoxy-6-methyl-4H-1-benzopyran-4-one (boeravinone Q, 9), an atropisomeric mixture of two rotenoid glycosides (3′,5-dihydroxy-2-hydroxymethyl-7-methoxy-6-methylisoflavone 2′-O-β-d-glucopyranoside, 11), a sesquiterpene lactone (4,10-dihydroxy-8-methoxyguai-7(11)-en-8,12-olide, 5) and a new phenylpropanoid glycoside (boerhaavic acid, 15).     

Developmental and Environmental Effects on Sesquiterpene Lactones in Cultivated Arnica montana L.

The amount of sesquiterpene lactones and the lactone profile of Arnica montana L. in flowering and seed formation stages in vitro and in vivo propagated from seeds of German, Ukrainian, and Austrian origin and grown in two experimental fields were studied. It was found that in vitro propagated 2‐year plants in full flowering stage accumulated higher amount of lactones in comparison to in vivo propagated 3‐year plants and to the seed formation stage, respectively. Helenalins predominated in in vivo propagated 2‐year or in vitro propagated 3‐year plants. 2‐Methylbutyrate (2MeBu) was the principal ester in the samples with prevalence of helenalins, while isobutyrate (iBu) was the major one in the samples with predominance of 11,13‐dihydrohelenalins. The results revealed that the environmental conditions on Vitosha Mt. are more suitable for cultivation of A. montana giving higher content of lactones.     

Phenol derivatives from the cold-seep fungus Aspergillus sydowii 10–31

Two bisabolane-type sesquiterpenoid phenols inclusive of the known (7 S)-flavilane A (1) and the new (7 S)− 4-iodo-flavilane A (2), along with a new tetraphenyl ether, bisviolaceol II (3), were isolated from the cold-seep fungus Aspergillus sydowii 10–31. Their structures were identified through spectroscopic methods, such as MS, IR, and NMR, and the absolute configurations of 1 and 2 were ascertained by comparison of ECD curves. Compounds 1 and 2 represent rarely encountered sulfur-bearing sesquiterpenes in nature, and the iodination in 2 makes it unique in particular. Additionally, 3 is the first tetraphenyl ether derivative from the fungal species A. sydowii. Compounds 1-3 inhibited the growth of several Vibrio bacteria and harmful microalgae.     

Studies on the cytotoxicity of miscellaneous compounds from Eupatorium betonicaeforme (D.C.) Baker (Asteraceae)

A detailed study on the cytotoxic effects of five known constituents isolated from the flowers and roots of Eupatorium betonicaeforme is reported, including 2,2-dimethyl-6-vinylchroman-4-one (1), 2-senecioyl-4-vinylphenol (2), 6-acetyl-2,2-dimethylchroman-4-one (3), (4E)-8beta-angeloyloxy-9beta,10beta-dihydroxy-1-oxogermacra-4,11(13)-dien-12,6alpha-olide (4), and 3beta-hydroxyicosan-1,5beta-olide (5). The sesquiterpene lactone 4 exhibited the highest cytotoxicity, with IC50 values ranging from 3.9 to 9.9 microM, showing some degree of cell selectivity. The antiproliferative activity of 4 was examined towards HL-60 cells, and found to diminish cell viability in a dose-dependent manner. Moreover, at all concentrations tested, there was a decrease in the number of cells capable of incorporating 5-bromo-2'-deoxyuridine (BrdU), indicating disruption of DNA synthesis. The morphological changes induced by 4 were compatible with apoptotic cell death. This work, thus, corroborates the anticancer potential of Eupatorium secondary metabolites.     

Juniperanol: First total synthesis and evaluation in Type 2 Diabetes disease

The first total synthesis of juniperanol, the tricyclic sesquiterpenoid enantiomer of α-cedrol is described. The synthesis relies on stereoselective gold-catalyzed Ohloff-type propargylic ester rearrangement performed on a 10 g scale, and a carbocationic cascade in the presence of acetyl methanesulfonate. The ability of juniperanol to interfere in glucose processes in different cell types is described.