Cytotoxic activity of sesquiterpene lactones from Inula britannica on human cancer cell lines

Five new sesquiterpene lactones (1–5) were isolated from Inula britannica collected in the wild from Serbia along with five known compounds (6–10). Sesquiterpene lactones were isolated using centrifugal partition chromatography followed by combination of flash chromatography and semi-preparative HPLC. Isolated compounds were screened for cytotoxic activity on four different human cancer cell lines and their multi-drug resistant counterparts, as well as on normal human keratinocytes. Sesquiterpene lactones showed similar cytotoxic activity toward drug sensitive and drug resistant cancer cell lines.     

Resorcylic acid lactones from the ginseng pathogen Ilyonectria mors-panacis

Ilyonectria mors-panacis, previously Cylindrocarpon destructans, is the main plant pathogen responsible for the fungal disease ginseng root rot. This economically important disease, also called disappearing root rot, reduces crop yields by an average of 30% at harvest. While the disease is well studied from ecological and genomic perspectives, the role of I. mors-panacis secondary metabolites in the disease process is not well understood. Our previous metabolomics study showed Ilyonectria strains that cause ginseng root rot produce mixtures of putative resorcylic acid lactones, whereas avirulent strains did not, and collectively synthesize fewer metabolites. To confirm these metabolomics findings, we isolated and characterized the secondary metabolites from I. mors-panacis DAOMC 251601, a strain that causes ginseng root rot. From its EtOAc soluble culture filtrate extract, eight resorcylic acid lactones (1-8), including chlorinated and non-chlorinated congeners, were characterized by HRMS and spectroscopic approaches (NMR, OR, UV). The structure of one new metabolite, named radicicol E (1), was elucidated and additional spectroscopic data for the known compound nordinonediol (2) are reported. Further, radicicol (9) production was confirmed by comparison to a standard. The roles that resorcylic acid lactones and the siderophore N,N′,N” triacetylfusarine C have in promoting Ilyonectria ginseng root rot are also discussed.     

Lactones from the pericarps of Litsea japonica and their anti-inflammatory activities

Five new lactones, litsenolide F₁ (1), lisealactone H₁ (10), lisealactone H₂ (11), akolactone D (13), and akolactone E (14), along with thirteen known compounds were isolated from the pericarps of Litsea japonica (Thunb.) Jussieu. Their chemical structures were elucidated by extensive spectroscopic analyses, including 1D and 2D NMR, HRMS, and chemical methods. The isolated compounds were evaluated for their inhibitory effects on NO production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Among them, 2-alkylidene-3-hydroxy-4-methylbutanolide derivatives (compounds 1–9) exhibited the most potent activity, with IC₅₀ values in the range of 2.9–12.8?μM. In additon, compounds 1, 3, 4, and 6 showed inhibition of iNOS and COX-2 expression in concentration-dependent manner. Compound 3 suppresses mRNA expression of iNOS, COX-2, IL-6, and TNF-α in LPS-stimulated RAW264.7 cells. Based on these evidence, the isolated lactones from L. japonica could be promissing candidates for the development of new anti-inflammatory agents.     

Lactones from Ficus auriculata and their effects on the proliferation function of primary mouse osteoblasts in vitro

Bioassay-guided fractionation of the petroleum ether, chloroform and EtOAc extracts of the stems of Ficus auriculata led to the isolation of five new 12-membered lactones (3R,4R)-4-hydroxy-de-O-methyllasiodiplodin (1), 6-oxolasiodiplodin (2) and ficusines A−C (3–5), together with three known related analogues (6–8). The structures of the new compounds were elucidated by comprehensive spectroscopic data. The absolute configurations of 3 and 8 were established by single crystal X-ray diffraction analysis. Compounds 3–5 represent the first 12-membered lactones with a quinone ring unit. Compounds 6 and 7 exhibited significant proliferation function of primary osteoblasts (OBs) in vitro. Especially, the promotion rate of 6 reached 151.55 ± 1.34% (P < 0.001) at the concentration of 100 μM.     

Supercritical fluid extraction assisted isolation of sesquiterpene lactones with antiproliferative effects from Centipeda minima

Pseudoguaianolide sesquiterpene lactones minimolides A (1), B (2), C (3) and D (4) and two guaianolide sesquiterpene lactones minimolides E (5) and F (6), along with seven known ones (7–13), were isolated from the supercritical fluid extract of Centipeda minima. The structures of these compounds were elucidated by extensive spectroscopic methods (IR, UV, HRESIMS, 1D-NMR and 2D-NMR), and the complete structure and stereochemistry of 1 was further confirmed by X-ray diffraction analysis. Compounds 1, 5–8, 11 and 13 displayed inhibitory activity against human nasopharyngeal cancer cells (CNE) with IC₅₀ values ranging from 1.1 to 20.3 μM. Compound 13 containing both α-methylene-γ-lactone and α, β-unsaturated cyclopentenone moieties exhibited even stronger inhibitory activity than that of cisplatin (positive control) through cell cycle arrest at G2/M phase. Isolation of six sesquiterpene lactones from Centipeda minima highlighted the potential of supercritical fluid extraction for enrichment of minor constituents for phytochemical study.     

Carbazole alkaloids with antiangiogenic activities from Clausena sanki

Two new carbazole alkaloids 1 and 2, and eleven known congeners 3–13 were isolated and identified from Clausena sanki for the first time. Their structures were elucidated on the basis of extensive UV, IR, MS, NMR spectroscopic data and comparison with literatures. The compounds 1–13 were evaluated by MTT assay to determine whether they decreased VEGF-mediated cell proliferation in HUVECs with Axitinib as positive control. Among them, compounds 1, 2, 6, 8, and 13 (μM) exhibited moderate antiangiogenic activities, which inhibited VEGF-induced HUVEC proliferation in vitro with IC₅₀ values of 12.1 (C.I. 8.2–15.2), 58.1 (C.I. 56.3–63.4), 13.7 (C.I. 9.2–15.4), 16.0 (C.I. 9.5–16.4), and 63.2 (C.I. 57.8–65.7) μM, respectively. Moreover, the antiangiogenic activities of compounds 1–13 were evidenced in vivo in the zebrafish embryo model. As a result, compounds 1, 2, 6, 8, and 13 showed effectively suppress angiogenesis. These research results may guide the search for new natural products with antiangiogenic attributes.     

Neue melampolide und cis,cis-germacranolide aus vertretern der subtribus melampodiinae

The investigation of four South American species of the tribe Heliantheae afforded in addition to known compounds 14 new sesquiterpene lactones, mostly belonging to the melampolides, but four being further examples of cis,cis-germacranolides. The stereochemistry is established by intensive ¹H-NMR studies and some chemical transformations. Some of the new lactones were only obtainable as inseparable mixtures of 2-methylbutyric and isovaleric esters. Furthermore a new acetylenic aldehyde was isolated. The chemotaxonomic situation is discussed especially with regard to the position of the genus Smallanthus.     

New triterpenoids from Leonurus japonicus (Lamiaceae)

Three new triterpenoids (1, 4, and 5), together with 17 known analogues, were isolated from the ethyl acetate soluble portion of the EtOH extract of Leonurus japonicus Houtt. Their structures were determined by spectroscopic analysis. All known triterpenoids were isolated from the genus Leonurus for the first time. Among them, triterpenoids 2–3, 9–12, and 16–20 were first isolated from the family Lamiaceae. Furthermore, the cycloartane, taraxastane, ursane, lupane, euphane, and dammarane types are reported here for the first time from the genus Leonurus.     

Anthraquinone derivatives from Rumex plants and endophytic Aspergillus fumigatus and their effects on diabetic nephropathy

Two new oxanthrone C-glycosides, patientosides A (14) and B (15), together with three known ones (11–13), were isolated from Rumex patientia. Their structures were identified on the basis of spectroscopic methods. The absolute configuration for 14 and 15 were deduced by analysis of their CD spectra and comparison with those of known similar compounds. Compounds 11–15, and 14 known anthraquinones (1–4, 6–10, 16–20) previously isolated from Rumex nepalensis, Rumex hastatus, and endophytic Aspergillus fumigatus, respectively, as well as a commercially available compound rhein (5) were evaluated for their inhibitory effects on IL-6 and extracellular matrix production in mesangial cells.     

Xanthones from the stems of Cudrania tricuspidata and their inhibitory effects on pancreatic lipase and fat accumulation

Nine new xanthones, cudracuspixanthones I - Q (12–14, 25, 32–36), and 30 known xanthones (1–11, 15–24, 26–31, 37–39) were isolated from the stems of Cudrania tricuspidata (Moraceae). The structures of isolated compounds were established by using 1D and 2D NMR in combination with HR-TOF-MS. Xanthones from the stems of C. tricuspidata exerted pancreatic lipase inhibitory activity. In addition, cudracuspixanthone P (35), a new xanthone, reduced the fat accumulation in liver cells stimulated with fatty acids. Therefore, these compounds might be beneficial in the treatment of metabolic diseases.     

Two new eudesmanolides from Inula racemosa and their bioactivities

Two new eudesmane-type sesquiterpene lactones, 1-one-4-epi-alantolactone (1) and 4α,13-dihydroxy-5,7(11)-eudesmadien-12,8-olide (2), were isolated from the roots of Inula racemosa, together with six known compounds (3–8). The cytotoxic activities against five human cancer cell lines had been tested and compounds 3, 6, 7 and 8 exhibited moderate cytotoxic activities. Compounds 4 and 8 showed potent in vitro activities against the release of β-glucuronidase in rat polymorphonuclear leukocytes (PMNs) induced by platelet-activating factor (PAF), with the inhibitory ratios 65.4% (P < 0.01) and 80.5% (P < 0.001), at concentration of 10 μM, respectively.     

Rare hydroperoxyl guaianolide sesquiterpenes from Pulicaria undulata

Pulicaria species, such as Pulicaria undulata, are rich in sesquiterpene lactones. The methylene chloride/methanol (1:1) extract of P. undulata resulted in the isolation of new sesquiterpenes (1–4), as well as previously reported metabolites (5–14). Structures were elucidated by spectroscopic analyses. Using a mouse peritoneal macrophage bioassay, lipopolysaccharide-induced nitric oxide inhibition was observed with the eudesman-type sesquiterpene 1β,4β-dihydroxy-5αH,7αH,8α-guaia-10(14),11(13)-dien-8β,12-olide (11) at an EC₅₀ of 7.2 μM.     

Streptophenazines I–L from Streptomyces sp. BCC21835

Four new streptophenazine derivatives I–L (2, 3, 4, 6), along with two known streptophenazines A (1) and B (5) were isolated from Streptomyces sp. BCC21835. The chemical structures have been determined based on NMR spectroscopic information and their optical rotation values. Apart from streptophenazines B and I, the isolated streptophenazines exhibited antibacterial activity against Bacillus cereus with IC₅₀ in a range of 6.25–12.50 μg/mL. These streptophenazines also showed low cytotoxicity against both cancerous (MCF-7, KB, NCI-H187) and non-cancerous (Vero) cells.     

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).     

The withanolides of Withania somnifera chemotypes I and II

Seven steroidal lactones of the withanolide series have been isolated as minor constituents of the leaves of Withania somnifera Dun. (Solanaceae) chemotype I, along with the major component withaferin A. Structures have been assigned to the new compounds: withanolide N (17α,27-dihydroxy-1-oxo-20R,22R-witha-2,5,14,24-tetraenolide) (6a) and withanolide O (4β,17α-dihydroxy-1-oxo-20R,22R-witha-2,5,8(14),24-tetraenolide) (7a). Similarly the leaves of W. somnifera chemotype II afforded three new withanolides along with the major component withanolide D (9a) and trace amounts of withanolide G (10). The new compounds are: 27-hydroxywithanolide D(4β,20α,27-trihydroxy-1-oxo-5β,6β-epoxy-20R,22R-witha-2,24-dienolide) (11a), 14α-hydroxywithanolide D (4β,14α,20α-trihydroxy-1-oxo-5β,6β-epoxy-20R,22R-witha-2,24-dienolide) (12a) and 17α-hydroxywithanolide D (4β,17β,20α-trihydroxy-1-oxo-5β,6β-epoxy-20S,22R-witha-2,24-dienolide) (13a). Whereas all the withanolides of chemotype I are unsubstituted at C-20 (20α-H), those of chemotype II possess an OH at this position (20α-OH).     

Esters of new oleanane-type triterpenoid saponins from Schefflera kwangsiensis

Eleven new oleanane-type triterpenoid saponins were isolated from the aerial parts of Schefflera kwangsiensis (1–11), together with nine esters (12–20) of known saponins. The structures of these compounds were elucidated on the basis of spectroscopic data analysis and chemical evidence. Furthermore, in in vitro assays, compounds 2, 3, 5, 7, 8, 11–13, 15, 17 and 18 (10 μM) exhibited moderate hepatoprotective activity against d-galactosamine-induced HL-7702 cell damage.     

Koanolides B-D,new sesquiterpene lactones from Koanophyllon gibbosum

Three new germacrane-type sesquiterpene lactones, koanolides B–D (1-3) have been isolated from the aerial parts of Koanophyllon gibbosum (Asteraceae), along with the previously reported sesquiterpene lactone koanolide A and the flavonoid eupatorin. The structures of the new compounds were elucidated using spectroscopic and spectrometric data analyses, including 1D and 2D NMR, and by comparison with known spectral data. The antiproliferative activities of the new compounds were evaluated in a panel of six representative human solid tumor cell lines and showed GI₅₀ values ranging from 1.3 to 16 μM for the new molecules.     

Chemical constituents from bulbs of Fritillaria pallidiflora Schrenk

A new steroidal alkaloid, 5α, 14α, 17β-cevanin-6-oxo-3β, 20β, 24β-triol(1), together with ten known compounds (2–11) were isolated from the bulbs of Fritillaria pallidiflora Schrenk. Their structures were determined on the basis of spectroscopic analysis and by comparison of their spectral data with those reported in the literature. Compounds 8, 9, 10 were obtained from the genus Fritillaria for the first time; Compounds 2, 3, 4 and 11 are isolated from this plant for the first time.     

Cytotoxic cardiac glycosides and coumarins from Antiaris toxicaria

Eight new cardiac glycosides/aglycones (antiaritoxiosides A–G, 1–7, and antiarotoxinin B, 8), two new coumarins (anticarins A–B, 41–42), and two new flavanones (antiarones L–K, 43–44) were isolated from trunk bark of Antiaris toxicaria together with 53 known compounds. The new structures were established by extensive analysis of spectroscopic data. Compound 1 (10-carboxy and 3α-hydroxy) and compounds 3–6 (10-hydroxy) contain unique substituents that are rarely found in cardiac glycosides. The cytotoxic effects of isolated compounds against ten human cancer cell lines, KB, KB-VIN, A549, MCF-7, U-87-MG, PC-3, 1A9, CAKI-1, HCT-9 and S-KMEL-2, were tested using the sulforhodamine B assay. Five compounds (12, 16, 20, 22, and 31) showed significant cytotoxicity against all ten cancer cell lines, with notable potency at the ng/mL level against some cell lines, which merits further development as clinical trial candidates.     

Antiproliferative and antimalarial anthraquinones of Scutia myrtina from the Madagascar forest

Bioassay-guided fractionation of an ethanol extract of a Madagascar collection of the bark of Scutia myrtina led to the isolation of three new anthrone–anthraquinones, scutianthraquinones A, B and C (1–3), one new bisanthrone–anthraquinone, scutianthraquinone D (4), and the known anthraquinone, aloesaponarin I (5). The structures of all compounds were determined using a combination of 1D and 2D NMR experiments, including COSY, TOCSY, HSQC, HMBC, and ROESY sequences, and mass spectrometry. All the isolated compounds were tested against the A2780 human ovarian cancer cell line for antiproliferative activities, and against the chloroquine-resistant Plasmodium falciparum strains Dd2 and FCM29 for antiplasmodial activities. Compounds 1, 2 and 4 showed weak antiproliferative activities against the A2780 ovarian cancer cell line, while compounds 1–4 exhibited moderate antiplasmodial activities against P. falciparum Dd2 and compounds 1, 2, and 4 exhibited moderate antiplasmodial activities against P. falciparum FCM29.