Cytotoxic furanosesquiterpenoids and steroids from Ircinia mutans sponges.

CONTEXT: Ircinia mutans Wilson (Irciniidae) is a sponge with antimicrobial and cytotoxic constituents. OBJECTIVE: Our objective was to characterise the cytotoxic constituents of two seasonal collections of I. mutans. MATERIALS AND METHODS: The sponges were extracted in methanol-dichloromethane and their constituents were purified and characterised using column chromatography, GC-MS, 1 D and 2 D NMR. Anti-proliferative activities of the compounds, were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay (0.25-100 µg/mL, 72 h) against leukaemia (MOLT-4), breast (MCF-7) and colon cancer (HT-29) human cells. RESULTS: Three furanosesquiterpoids; furodysin (1), ent-furodysinin (2) and furoircin (3) and ten sterols were characterised in I. mutans, for the first time. Cholesterol (4), cholesta-5, 7-dien-3ß-ol (5) and ergosterol (6) were determined in the sponge from the winter collections, while cholesta-5, 22-dien-3ß-ol (7), 24-methyldesmosterol (8), campesterol (9), stigmasterol (10), γ-ergostenol (11), chondrillasterol (12) and γ-sitosterol (13) were detected in the summer samples. The steroids from the winter collection exhibited cytotoxic activity with IC50 values of 13.0 ± 0.9, 11.1 ± 1.7 and 1.1 ± 0.4 µg/mL, against the mentioned cancer cell lines, respectively, while those from the summer sample, showed greater activity, IC50 = 1.1 ± 0.2 µg/mL against MOLT-4. The purified steroids showed potent MOLT-4 cytotoxic activity, IC50 values = 2.3-7.8 µg/mL. DISCUSSION AND CONCLUSION: The present study suggests that I. mutans is a rich source of cytotoxic steroids, and introduces 3 as new natural product. Considering the high cytotoxic activity of the steroids, these structures could be candidates for anticancer drug development in future research.

Antidiabetic and cytotoxic polyhydroxylated oleanane and ursane type triterpenoids from Salvia grossheimii.

Two polyhydroxylated oleanane and seven ursane triterpenoids were isolated from aerial parts of Salvia grossheimii. The chemical structures of the undescribed triterpenoids (1-6) were characterized using 1 and 2 D NMR and ESI-MS spectral data as; 2α, 3ß, 11α -trihydroxy-olean-12- ene (1), 2α, 3ß, 11α-trihydroxy-olean-18-ene (2), 2α- acetoxy-urs-12-ene-3ß, 11α, 20ß-triol (3), 3-keto-urs-12-ene-1ß, 11α, 20ß -triol (4), 2α, 3ß-diacetoxy-urs-12-ene-1ß, 11α, 20ß -triol (5), and 3ß-acetoxy-urs-12-ene-1ß, 11α, 20ß -triol (6). All compounds were evaluated for the in vitro α-glucosidase inhibitory and cytotoxic activities against MCF-7 human cancer cell line. Compounds 1, 2, 4, and 6 showed in vitro α-glucosidase inhibitory activity with IC50 = 43.6-198.4 µM, which were more potent than the antidiabetic medicine, acarbose. The remaining compounds; 3, and 7-9 showed potent cytotoxic activity (IC50 = 6.2-31.9 µM) against the cancerous cell line, while the potent α-glucosidase inhibitors were inactive. Molecular docking analysis and kinetic studies were applied to investigate the structure activity relationships and mechanisms of the human and Saccharomyces cerevisiae α-glucosidase inhibitory of the purified compounds. Comparing the high cytotoxicity and α-glucosidase inhibitory of the oleanane and ursane type triterpenoids suggest them as potential lead compounds for further research in anticancer and antidiabetic research.

Biosynthesis of 8-O-Methylated Benzoxazinoid Defense Compounds in Maize.

Benzoxazinoids are important defense compounds in grasses. Here, we investigated the biosynthesis and biological roles of the 8-O-methylated benzoxazinoids, DIM2BOA-Glc and HDM2BOA-Glc. Using quantitative trait locus mapping and heterologous expression, we identified a 2-oxoglutarate-dependent dioxygenase (BX13) that catalyzes the conversion of DIMBOA-Glc into a new benzoxazinoid intermediate (TRIMBOA-Glc) by an uncommon reaction involving a hydroxylation and a likely ortho-rearrangement of a methoxy group. TRIMBOA-Glc is then converted to DIM2BOA-Glc by a previously described O-methyltransferase BX7. Furthermore, we identified an O-methyltransferase (BX14) that converts DIM2BOA-Glc to HDM2BOA-Glc. The role of these enzymes in vivo was demonstrated by characterizing recombinant inbred lines, including Oh43, which has a point mutation in the start codon of Bx13 and lacks both DIM2BOA-Glc and HDM2BOA-Glc, and Il14H, which has an inactive Bx14 allele and lacks HDM2BOA-Glc in leaves. Experiments with near-isogenic maize lines derived from crosses between B73 and Oh43 revealed that the absence of DIM2BOA-Glc and HDM2BOA-Glc does not alter the constitutive accumulation or deglucosylation of other benzoxazinoids. The growth of various chewing herbivores was not significantly affected by the absence of BX13-dependent metabolites, while aphid performance increased, suggesting that DIM2BOA-Glc and/or HDM2BOA-Glc provide specific protection against phloem feeding insects.

Duckweed for Human Nutrition: No Cytotoxic and No Anti-Proliferative Effects on Human Cell Lines.

Duckweeds (Lemnaceae) possess good qualitative and quantitative profiles of nutritional components for its use as human food. However, no studies have been conducted on the probable presence or absence of any adverse effects. The extracts from seven duckweed species (Spirodela polyrhiza, Landoltia punctata, Lemna gibba, Lemna minor, Wolffiella hyalina, Wolffia globosa, and Wolffia microscopica) covering all five genera of the plant family were herewith tested for cytotoxic effects on the human cell lines HUVEC, K-562, and HeLa and for anti-proliferative activity on HUVEC and K-562 cell lines. From these assays, it is evident that duckweeds do not possess any detectable anti-proliferative or cytotoxic effects, thus, the high nutritional value is not diminished by such detrimental factors. The present result is a first step to exclude any harmful effects of highly nutritious duckweed for human.

Phenylphenalenones protect banana plants from infection by Mycosphaerella fijiensis and are deactivated by metabolic conversion.

Phenylphenalenones, polycyclic aromatic natural products from some monocotyledonous plants, are known as phytoalexins in banana (Musa spp.). In this study, (1) H nuclear magnetic resonance (NMR)-based metabolomics along with liquid chromatography and mass spectrometry were used to explore the chemical responses of the susceptible 'Williams' and the resistant 'Khai Thong Ruang' Musa varieties to the ascomycete fungus Mycosphaerella fijiensis, the agent of the black leaf Sigatoka disease. Principal component analysis discriminated strongly between infected and non-infected plant tissue, mainly because of specialized metabolism induced in response to the fungus. Phenylphenalenones are among the major induced compounds, and the resistance level of the plants was correlated with the progress of the disease. However, a virulent strain of M. fijiensis was able to overcome plant resistance by converting phenylphenalenones to sulfate conjugates. Here, we report the first metabolic detoxification of fungitoxic phenylphenalenones to evade the chemical defence of Musa plants.

Highly Oxygenated Sesquiterpene Lactones from Cousinia aitchisonii and their Cytotoxic Properties: Rhaserolide Induces Apoptosis in Human T Lymphocyte (Jurkat) Cells via the Activation of c-Jun n-terminal Kinase Phosphorylation.

Infrared-guided chromatographic fractionation of sesquiterpene lactones from the extracts of Cousinia aitchisonii and Cousinia concolor led to the isolation of five pure compounds. A new sesquiterpene lactone, namely, aitchisonolide, and two known sesquiterpene lactones (desoxyjanerin and rhaserolide) were isolated from C. aitchisonii and two known lignans (arctiin and arctigenin) from C. concolor. The structures of these compounds were elucidated by one-dimensional and two-dimensional nuclear magnetic resonance techniques, as well as high-resolution mass spectrometry. The purified and characterized compounds were subjected to cytotoxicity assay. The sesquiterpene lactones desoxyjanerin and rhaserolide showed significant cytotoxic activities against five different cancer cell lines and the normal human embryonic kidney cell line. Rhaserolide was chosen to evaluate the possible mechanism of action. Western blot analysis revealed that rhaserolide could induce apoptosis in Jurkat cells via the activation of c-Jun n-terminal kinase phosphorylation.

Cytotoxic activity and chemical constituents of Anthemis mirheydari.

Context The genus Anthemis L. (Asteraceae) comprises about 195 species which are widely used in the pharmaceutical, cosmetic and food industries. Objective Anthemis mirheydari Iranshar, an endemic plant from Iran, was investigated for its cytotoxic properties and chemical constituents. Materials and methods The whole parts of the plant (320 g) were extracted by dichloromethane and methanol for four days, successively. The cytotoxic activity of both dichloromethane and methanol extracts were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric methods against three human cancer cell lines including LS180, MCF-7 and MOLT-4. Different concentrations (10-100 µg/mL) of the plant extracts were tested to obtain IC50 values. The dichloromethane extract of A. mirheydari was subjected to silica gel-column and thin layer chromatography for purification of its chemical constituents and the isolated compounds were further tested against MOLT-4 cells. The structures of the pure compounds were elucidated using different spectral data including nuclear magnetic resonance and electron impact mass spectra. Results The IC50 values of the dichloromethane extract were 30.8 ± 6.7, 25.2 ± 6.5 and 8.6 ± 1.1 µg/mL (means ± standard error) for the above-mentioned cell lines, respectively. Two triterpenoids, taraxasterol (1) and pseudotaraxasterol (2), one sterol, ß-sitosterol (3) and one coumarin, 7-methoxycoumarin (4) were isolated from the extract. The IC50 of the mixture of compounds 1 and 2 as well as compounds 3 and 4 were higher (>100 µM) than that reported for the dichloromethane extract against MOLT-4 cells. Conclusion The dichloromethane extract was the most active one among the tested material.

Phytochemical Analysis and Biological Activity of Salvia compressa Vent.

Background: Salvia extracts have various biological activities and are rich sources of bioactive metabolites. Objectives: We identified five phytochemicals from S. compressa extract and assessed its biological properties. Methods: The plant's shoots were extracted using dichloromethane, and the constituents were isolated using column chromatography. High-resolution NMR spectroscopy characterized the chemical structures of the compounds (1 - 5). The cytotoxic effect of the extract was examined against MCF-7 cells by MTT reduction assay, while cisplatin was tested as a reference cytotoxic compound. The antibacterial activity was assessed using nutrient broth micro-dilution (NBMD), and chloramphenicol was used as the positive control. Results: Citrostadienol (1), ß-sitosterol (2), two glyceride esters of linolenic, linoleic, and palmitic acids (3, 4), and geraniol (5) were isolated from S. compressa for the first time. The extract showed activity against MCF-7 breast cancer cells and reduced cell viability to 68.2 ± 13.1% compared to the control drug at the concentration of 50 µg/mL, while it was not active against seven test bacteria. Conclusions: The anti-complementary activity of the isolated steroids suggests S. compressa for future anti-inflammatory research.

Cytotoxic abietane-type diterpenoids from roots of Salvia spinosa and their in Silico pharmacophore modeling.

The roots of Salvia spinosa L. (Lamiaceae) were extracted with hexane, dichloromethane (DCM) and ethyl acetate. The DCM extract exhibited cytotoxic activity (IC50 32.7 µg/mL) against MFC-7 breast cancer cell line in MTT colorimetric bioassay. Ferruginol (1), taxodione (2), 12-deoxy-6-hydroxy-6,7-dehydroroyleanone (3), 14-deoxycoleon U (4), 15-deoxyfuerstione (5) and taxodone (6) were isolated from the DCM roots extract. Their structures were elucidated by a combination of spectroscopic analyses including EIMS and 1H- and 13C NMR spectra. The cytotoxicity of compound 3 was determined against MCF-7 and K562 cell lines and compared with the other compounds. A pharmacophore model was built based on potent input compounds to resolve important pharmacophore features responsible for cytotoxic activity of the isolated compounds.

Novel foldamer structural architecture from cofacial aromatic building blocks.

This communication demonstrates the utility of peri-substituted 1,8-diphenylnaphthalene as an effective building block for the construction of novel conformationally ordered synthetic oligomers displaying cofacial structural features.

Sterically controlled naphthalene homo-oligoamides with novel structural architectures.

Herein we report novel naphthalene homo-oligoamides, derived from 4-amino-3-methoxy-naphthalene-2-carboxylic acid and 4-amino-1-methoxy-naphthalene-2-carboxylic acid as monomer building blocks, that display an anti-periplanar arrangement of the naphthyl rings, primarily induced by steric interactions between adjacent groups and functionalities.

The roots of Salvia rhytidea: a rich source of biologically active diterpenoids.

Sahandinone (1), 12-deoxysalvipisone (2), miltirone (3), 7α-acetoxyroyleanone (4), and labda-7,14-dien-13-ol (5) were isolated from the roots of Salvia rhytidea Benth. (Lamiaceae). Their structures were elucidated by a combination of spectroscopic analyses including EIMS and NMR. The 13C NMR spectroscopic data were revised for the quaternary carbons of both 1 and 3 with the help of HMBC spectra in respect to the spectral data previously reported in the literature. Compounds 1 and 3, two very potent anticancer agents, were isolated in high yields from the roots of the plant. The biological activities of the plants' constituents were reported in the literature as antimicrobial, cytotoxic and antimalarial are discussed in this article.

Identification, quantification, spatiotemporal distribution and genetic variation of major latex secondary metabolites in the common dandelion (Taraxacum officinale agg.).

The secondary metabolites in the roots, leaves and flowers of the common dandelion (Taraxacum officinale agg.) have been studied in detail. However, little is known about the specific constituents of the plant's highly specialized laticifer cells. Using a combination of liquid and gas chromatography, mass spectrometry and nuclear magnetic resonance spectrometry, we identified and quantified the major secondary metabolites in the latex of different organs across different growth stages in three genotypes, and tested the activity of the metabolites against the generalist root herbivore Diabrotica balteata. We found that common dandelion latex is dominated by three classes of secondary metabolites: phenolic inositol esters (PIEs), triterpene acetates (TritAc) and the sesquiterpene lactone taraxinic acid ß-D-glucopyranosyl ester (TA-G). Purification and absolute quantification revealed concentrations in the upper mgg(-1) range for all compound classes with up to 6% PIEs, 5% TritAc and 7% TA-G per gram latex fresh weight. Contrary to typical secondary metabolite patterns, concentrations of all three classes increased with plant age. The highest concentrations were measured in the main root. PIE profiles differed both quantitatively and qualitatively between plant genotypes, whereas TritAc and TA-G differed only quantitatively. Metabolite concentrations were positively correlated within and between the different compound classes, indicating tight biosynthetic co-regulation. Latex metabolite extracts strongly repelled D. balteata larvae, suggesting that the latex constituents are biologically active.

Bioassay guided purification of cytotoxic natural products from a red alga Dichotomaria obtusata

ABSTRACT Different solvent extracts of Dichotomaria obtusata (J. Ellis & Solander) Lamark, Galaxauraceae, a red algae collected from the coast of Bushehr in the Persain Gulf, was investigated for its cytotoxic properties and chemical constituents. The fresh alga, after extraction with methanol and dichloromethane were combined and partitioned between water, dichloromethane and ethyl acetate. The above fractions were then tested against MOLT-4 (human lymphoblastic leukemia) cancer cell line. The IC50 values of the dichloromethane and ethyl acetate layers of the crude extract were 29.8 ± 3.1 and 30.6 ± 7.9 µg/ml against MOLT-4 cells, respectively, while the water layer showed a week activity with IC50 > 50 µg/ml. After fractionation of the active extracts using open column chromatography over silica gel and preparative thin layer chromatography purification, two terpenoid derived compounds, trans-phytol palmitate and γ-tocopherol were isolated from the dichloromethane and ethyl acetate extracts. The structures of the compounds were elucidated using different spectral data including 1H NMR, 13C NMR, HSQC, HMBC and EI-MS. The IC50 values of compounds trans-phytol palmitate, γ-tocopherol and an undetermined mixture of compounds (F-13-14) were determined as 43.4 ± 1.6, – and 20.3 ± 6.2 µg/ml against LS180 (human colon adenocarcinoma); 53.2 ± 9.3, >100 and 27.6 ± 6.9 µg/ml against MCF-7 (human breast adenocarcinoma) and 40.0 ± 4.1, 48.8 ± 1.8 and 15.9 ± 0.3 µg/ml against MOLT-4 cell lines, respectively, which were comparable to the IC50 values of standard anticancer agent, cisplatin against the same cell lines. The red algae collected from the Persian Gulf contained substances that could inhibit the growth of human cancer cell lines and may represent a natural source for the discovery of novel anticancer agents.