Bioactive steroidal glycosides from the marine sponge Erylus lendenfeldi

Bioassay-guided fractionation of the methanol extract of Erylus lendenfeldi using engineered strains of budding yeast (Saccharomyces cerevisiae) has resulted in the isolation of the known compound eryloside A (1) and two new compounds, erylosides K (2) and L (3). The structures were established based mainly on 1D and 2D NMR data. The absolute stereochemistry of eryloside A, which had never been fully characterized, was determined using the modified Mosher's method. The absolute stereochemistry of eryloside K was determined by comparison with tetrahydroeryloside A. Compounds 1-3 exhibited selective cytotoxicity against a yeast strain (Δrad50) deficient in double strand break (DSB) repair.     

Pileamartines A and B: Alkaloids from Pilea aff. martinii with a new carbon skeleton

Two novel alkaloids, with an unprecedented carbon skeleton, pileamartines A (1) and B (2), together with the known alkaloid, julandine (I-a) were isolated from the alkaloidal fraction of Pilea aff. martinii leaves. Their structures were established by spectral data analysis, including MS and 2D NMR. The absolute configurations of 1 and 2 were suggested by comparison of their experimental and calculated electronic circular dichroism spectra. Compound 2 exhibited weak inhibitory activity against the α-glucosidase enzyme with an inhibition of 11% at a concentration of 200?µM. These compounds were not cytotoxic against several cancer cell lines even at a concentration of 150?µM.     

Novel cytotoxic constituents of Orthosiphon diffusus

Chemical investigation on Orthosiphon diffusus resulted in the isolation of four relatively rare, novel polychiral furanopyrans, orthodiffenes A-D (1-4) which were characterized from detailed studies of their 1D and 2D NMR spectra. The X-ray crystallographic analysis of orthodiffene A (1) was accomplished. The in vitro cytotoxic activity of orthodiffenes A-C (1-3) was tested against Jurkat and HL-60 cells using camptothecin as a positive control. Orthodiffenes A (1) and B (2) showed comparable activity to camptothecin against HL-60 and Jurkat cells, respectively.     

New premyrsinane-type diterpene polyesters from Euphorbia falcata

Four new premyrsinane-type diterpenes (1-4) were isolated from the methanol extract of the whole, undried plant of Euphorbia falcata. Their structures were determined by a combination of 1D and 2D NMR (COSY, HMBC, HSQC and NOESY) techniques and mass spectral data as di-, tetra-, penta- and hexaesters of diterpene polyols, esterified with acetic, benzoic, propanoic, isobutanoic and n-hexanoic acids. One of the compounds contains a rare hemiacetal moiety. This type of diterpenes was previously detected only in four Euphorbia species (Euphorbia aleppica, Euphorbia decipiens, Euphorbia macroclada and Euphorbia pithyusa subsp. cupani).     

Humulene derivatives from Saharian Asteriscus graveolens

Three new sesquiterpene-humulenes, (?)- asteriscunolides I (1), J (2) and (?)-(2Z,6E,9Z)-8-oxo-1α-acetoxy-2,6,9-humulatrien-12-oic acid (3) were isolated from the leaves-flowers of the Saharan medicinal plant Asteriscus graveolens along with six known compounds. The structures of the compounds were determined on the basis of spectroscopic mono and bidimensional NMR, mass spectrometry and by single-crystal X-ray diffraction. Compounds 1–3 were evaluated for cytotoxic assay, no significant activity was detected.     

Andrographolactone, a unique diterpene from Andrographis paniculata

Andrographolactone (1), possessing an unprecedented diterpene skeleton, was isolated from the EtOAc extract of the aerial parts of Andrographis paniculata. Its structure was established by NMR, IR, UV, and HRESIMS data and subsequently confirmed by X-ray diffraction analysis. A possible biogenetic pathway of 1 was also proposed. Bioassay showed that 1 exhibited cytotoxic activity.     

Induced secondary metabolites from the endophytic fungus Aspergillus versicolor through bacterial co-culture and OSMAC approaches

Two new cryptic 3,4-dihydronaphthalen-(2H)-1-one (1-tetralone) derivatives, aspvanicin A (1) and its epimer aspvanicin B (2), as well as several known cryptic metabolites (3–8), were obtained from the ethyl acetate extract of the co-culture of the endophytic fungus Aspergillus versicolor KU258497 with the bacterium Bacillus subtilis 168 trpC2 on solid rice medium. When A. versicolor was cultured axenically in liquid Wickerham medium supplemented with 3.5% DMSO, an additional three known secondary metabolites (9–11) were isolated that were lacking when the fungus was fermented on rice medium. The structures of the new compounds were elucidated using one- and two-dimensional NMR spectroscopy as well as HRESIMS. The relative and absolute configurations of 1 and 2 were determined by the combination of NMR and electronic circular dichroism (ECD) analysis aided by DFT conformational analysis and TDDFT-ECD calculations. The ECD calculations revealed that although the sign of the blue-shifted overlapping n-π¹ ECD transition follows the helicity rule of cyclic aryl ketones, the calculation of low-energy conformers and ECD spectra was necessary to determine the stereochemistry. All metabolites were assessed for their antibacterial and cytotoxic activities; one of the new diastereomers, compound 2, showed moderate cytotoxic activity against the mouse lymphoma cell line L5178Y.     

Njaoamines A-F, new cytotoxic polycyclic alkaloids from the haplosclerid sponge Reniera sp.

Six new cytotoxic polycyclic alkaloids containing an 8-hydroxyquinoline moiety, njaoamines A-F (1-6), have been isolated from the 2-propanol extract of the sponge Reniera sp. collected in Tanzania. Their structures were determined by extensive analysis of their spectroscopic features, particularly 1D and 2D NMR spectra recorded in Py-d₅. Cytotoxicity of the compounds isolated was evaluated against a panel of three human tumor cell lines.     

Three novel nortriterpenoids from Notochaete hamosa Benth. (Labiatae)

Three nortriterpenoids, notohamosin A (1), B (2) and C (3) with novel skeleton, and eight known compounds were isolated from the ethanol extract of the whole plants of Notochaete hamosa Benth. (Labiatae). On the basis of spectral evidence including 1D, 2D NMR, IR and MS data, their structures were elucidated. The relative configurations of compounds 1, 2 and 3 were determined according to NOESY experiments.     

Piperazirum, a novel bioactive alkaloid from Arum palaestinum Boiss.

A novel alkylated piperazine (3α,5α-diisobutyryl-6α-isopropyl-piperazine-2-one, 1) has been isolated from the n-butanol soluble part of the leaves extract of Arum palaestinum Boiss., the chemical structure and the relative stereochemistry of 1 were elucidated on the basis of 1D and 2D NMR spectroscopic data. Piperazirum showed a significant cytotoxicity against cultured tumor cell lines in vitro.     

Isolation, structure elucidation and biological activity of hederacine A and B, two unique alkaloids from Glechoma hederaceae

Preparative HPLC purification of a methanol extract of the aerial parts of Glechoma hederaceae has yielded two unique alkaloids, hederacine A (1) and hederacine B (2). The structures of these compounds were established unequivocally by UV, IR, MS and a series of 1D and 2D NMR analyses. These alkaloids were inactive against any of the 11 bacterial species at test concentrations, but showed prominent toxicity in the brine shrimp lethality assay (LC₅₀s=3.2, 14.0 and 2.7 μg/mL, respectively, for 1, 2 and the positive control, podophyllotoxin).     

Sassafrins A-D, new antimicrobial azaphilones from the fungus Creosphaeria sassafras

Four new azaphilones named sassafrins A-D (1-4) were isolated from the methanol extract of the stromata of the fungus Creosphaeria sassafras (Xylariaceae, Ascomycetes). Their structures were elucidated by 2D NMR, HR-MS, IR, UV and CD spectroscopy. Sassafrin D (4) possesses a novel skeleton and its biosynthetic pathway is also discussed. In addition, all compounds showed broad-spectrum antimicrobial activity. Their apparently unique occurrence in C. sassafras supports the status of this fungus as a member of a distinct genus within the Xylariaceae, coinciding with molecular and morphological traits.     

Hexamollamide, a hexapeptide from an Okinawan ascidian Didemnum molle

The bioassay-guided fractionation of the cytotoxic constituents of the Okinawan ascidian Didemnum molle led to the isolation of hexamollamide (1), a hexapeptide. The gross structure and relative stereostructure of 1 were established by spectroscopic analysis including 2D NMR techniques and single-crystal X-ray diffraction analysis. The absolute stereostructure was determined by chiral HPLC analysis of acid hydrolysates of 1. Hexamollamide (1) exhibits moderate cytotoxicity against HeLa S₃ cells.     

New borrelidin derivatives from an endophytic Streptomyces sp.

Three new borrelidin-type macrolactones, designated as borrelidins J?L (4–6), together with borrelidin A (1), borrelidin E (2), and 12-desnitrile-12-carboxyl-borrelidin (3) were isolated from a plant endophytic Streptomyces sp. NA06554. Their structures were determined by extensive spectroscopic analysis including HRESIMS, 1D and 2D NMR data. The antibacterial activities for compounds 1–6 were examined. Borrelidins A (1) and L (6) showed potent and moderate antibacterial activity against Micrococcus luteus, respectively, whereas other derivatives (2–5) are almost inactive, which allows us to propose a plausible structure-activity relationship.     

Antitrypanosomal pyridoacridine alkaloids from the Australian ascidian Polysyncraton echinatum

Bioassay-guided fractionation of the crude CH₂Cl₂/MeOH extract from the Australian ascidian Polysyncraton echinatum led to the isolation of a new pyridoacridine alkaloid, 12-deoxyascididemin (1), along with two known analogues, ascididemin (2) and eilatin (3). The structure of 1 was determined following extensive analysis of 1D/2D NMR and MS data. Biological evaluation showed that compounds 1-3 are potent antitrypanosomal agents with IC₅₀ values of 0.077, 0.032, and 1.33 μM against Trypanosoma brucei brucei, respectively.     

Infectopyrone, a potential mycotoxin from Alternaria infectoria

A new metabolite, infectopyrone (1), has been isolated from the filamentous fungus Alternaria infectoria. The structure of 1 was elucidated by analysis of 2D NMR spectroscopic data. Compound 1 is an α-pyrone resembling known toxins, and is a useful phenotaxonomic marker for the A. infectoria species-group. Infectopyrone (1) was also produced by species within Stemphyllium and Ulocladium, and found in mouldy food.     

Malettinin A: a new antifungal tropolone from an unidentified fungal colonist of Hypoxylon stromata (NRRL 29110)

Malettinin A (1) has been isolated from cultures of an unidentified fungus encountered as a colonist of Hypoxylon stromata. The structure of 1 was proposed by analysis of NMR and MS data, and confirmed by X-ray diffraction analysis of a methanol adduct. Malettinin A shows significant activity in assays against Aspergillus flavus.     

New cytotoxic halogenated sesquiterpenes from the Egyptian sea hare, Aplysia oculifera

Two new sesquiterpenes, oculiferane (1) and epi-obtusane (2) have been isolated and identified from an acetone extract of the digestive gland of the sea hare, Aplysia oculifera. The structures were elucidated by spectroscopic analysis including HREIMS, ¹H, ¹³C, DEPT, ¹H–¹H COSY, HMQC, and HMBC NMR; the relative configuration was confirmed by X-ray analysis. Compounds 1 and 2 exhibited cytotoxic activity in vitro against several human cancer cell lines with IC₅₀ values in the low μg/ml range.     

Isolation, structure elucidation and bioactivity of schischkiniin, a unique indole alkaloid from the seeds of Centaurea schischkinii

Reversed-phase HPLC analysis of the methanol extract of the seeds of Centaurea schischkinii afforded a novel indole alkaloid, named schischkiniin (1), together with four lignans, arctiin (2), matairesinoside (3), matairesinol (4), and arctigenin (5), and three flavonoids, astragalin (6), afzelin (7) and apigenin (8). While the structure of schiskiniin (1) was established unequivocally by UV, HRFABMS and a series of 1D and 2D NMR analyses, all known compounds were readily identified by comparison of their spectroscopic data with literature data. The free radical scavenging properties of these compounds were assessed using the DPPH assay, and their general toxicity and cytotoxicity were evaluated, respectively, by brine shrimp lethality and MTT cytotoxicity assays with CaCo-2 colon cancer cell lines. Arctigenin (5) exhibited promising in vitro anticancer activity (IC₅₀=7 μM) while with schischkiniin (1) the activity was of moderate level (IC₅₀=76 μM).     

Two novel tricyclic diterpenoids from Isodon rubescens var. taihangensis

Two novel tricyclic diterpenoids rubescensins U (1) and V (2) were isolated from the leaves of Isodon rubescens var. taihangensis. They were elucidated as a 8,15-seco-ent-kauranoid and an ent-abietanoid, respectively, by 1D and 2D NMR spectra, and single crystal X-ray analysis. Compound 1 is the first example of an 8,15-seco-ent-kaurane from the plants genus Isodon. A discussion of their biogenesis is described.