Damipipecolin and damituricin, novel bioactive bromopyrrole alkaloids from the Mediterranean sponge Axinella damicornis

Two new bromopyrrole alkaloids, damipipecolin (1) and damituricin (2), have been isolated from the Mediterranean sponge Axinella damicornis, and their structures established through spectroscopic methods. Compounds 1 and 2 extend the structural variety of the so far known pyrrole alkaloids; in these compounds, the 4-bromopyrrole 2-carboxylic acid is directly condensed with a non-protein cyclic alpha-amino acid, the (2R, 4R)-trans-4-hydroxypipecolic acid and (2R, 4R)-cis-N,N'-dimethyl-4-hydroxyproline (D-turicine) in 1 and 2, respectively. Compounds 1 and 2 were found to display a modulating effect of the serotonin receptor activity in vitro.     

Novel secopyrrolizidine alkaloids from Crotalaria verrucosa

Crotaverrine and O-acetylcrotaverrine, isolated from the seeds of C. verrucosa Linn., have been shown by spectroscopy and chemical evidence to be the macrocyclic diesters of otonecine and diastereoisomeric integerrinecic acid. Hitherto, diastereoisomeric integerrinecic acid esters were not known to occur in nature.     

Further characterization of the orange carotenoid protein extracted from the marine demosponge Axinella verrucosa

The orange coloration of the marine sponge A. verrucosa is provided by some carotenoids widespread in the ectosome and mesohyl of this sponge. These carotenoids are bound to a glyco(lipo)protein forming a non covalent complex. Six carotenoids are bound to the glyco(lipo)protein, but only alpha-carotene was identified by HPLC. The aminoacid composition is quite different from those previously reported in Porifera. The content of Ser and Gly and the total polar residues are high. The presence of Met and Pro was not evidenced. Some unusual aminoacids were detected, of which only Taurine was probably identified.     

Monobromoisophakellin, a new bromopyrrole alkaloid from the Caribbean sponge Agelas sp

A detailed analysis of the chemical constituents of a Caribbean specimen of Agelas sp. was carried out. Four brominated compounds (1-4) were isolated and one of them was identified as a new bromopyrrole metabolite, monobromoisophakellin (1). The structure of 1 was determined using spectroscopic methods. All compounds were tested for their antifeedant activity against the Caribbean reef fish Thalassoma bifasciatum in an aquarium assay.     

Corrugoside, a new immunostimulatory alpha-galactoglycosphingolipid from the marine sponge Axinella corrugata

Corrugoside (1a), a new immunostimulatory triglycosilated alpha-galactoglycosphingolipid, was isolated from the marine sponge Axinella corrugata, and its structure determined by spectral analysis and chemical degradation. Compound 1a activated murine NKT cells in vitro, with a potency of about 2 logs lower than that of alphaGalCer. Four stereoisomeric glycosphingolipids (2a-2d) were also obtained, beta-glucosylceramides bearing unusual endoperoxide and allylic hydroperoxide functionalities on the sphinganine chain. They were shown to be photooxidation artifacts of the known glycosphingolipids 3, also present in the sponge. A possible role of compound 3 as a singlet oxygen scavenger to protect the organism from oxidative damage is proposed.     

New anticancer bastadin alkaloids from the sponge Dendrilla cactos

Two new bastadin alkaloids, bastadins-22 (1) and 23 (2), together with six known bastadins, bastadins-6 (3), -12 (4) (formerly basatadin-9), -14 (5), -15 (6), -16 (7), -19 (8), and a common steroid cholesterol were isolated from the sponge Dendrilla cactos. The structures of the isolates were established by the study of extensive spectroscopic analysis (1D and 2D NMR and MS data). Anticancer activity of the isolates has been carried out against Sup-T(1) cancer cells (T cell lymphoma).     

New bioactive steroidal alkaloids from Buxus hyrcana

Phytochemical studies on the crude methanolic extract of Buxus hyrcana, collected from Iran, resulted in the isolation of two new steroidal alkaloids, (+)-O6-buxafurandiene (1) and (+)-7-deoxy-O6-buxafurandiene (2) along with four known steroidal bases, (+)-benzoylbuxidienine (3), (+)-buxapapillinine (4), (+)-buxaquamarine (5) and (+)-irehine (6). The structures of these new and known compounds were established with the aid of extensive NMR spectroscopic studies. Compounds 1 and 2 belong to the rarely occurring class of Buxus alkaloids having a tetrahydrofuran ring incorporated in their structures. Compounds 1-6 exhibited acetylcholinesterase enzyme inhibitory activity.     

ATP N-glycosidase - a novel ATP-converting activity from a marine sponge Axinella polypoides.

A novel nucleosidase enzymatic activity was discovered in the marine sponge Axinella polypoides. This enzyme, designated as ATP N-glycosidase, converts adenosine-5'-triphosphate into adenine and ribose-5-triphosphate. The crude extract of A. polypoides was capable of hydrolysing 25 micro mol ATP.min-1 per g wet weight of sponge. The catalytic activity of a sponge crude extract per mg total protein is comparable with specific activities of purified plant adenosine and bacterial AMP nucleosidases. The preferred substrate for the novel enzyme is ATP but any compound containing adenosine-5'-diphosphoryl fragment is also cleaved. The biochemical properties (Km, Kip, environmental requirements) of ATP N-glycosidase show similarities with previously described adenine-specific nucleosidases; however, the pattern of its biochemical characteristics does not match with that of any of those enzymes.     

New potently bioactive alkaloids from Crinum erubescens

Antimalarial bioassay-guided fractionation of the swamp lily Crinum erubescens led to the isolation of four compounds with potent antiplasmodial activity. Compounds 1 and 2 were determined from their spectroscopic data to be the known pesticidal compound cripowellin A and the known pesticidal and antiproliferative compound cripowellin B. 1D and 2D-NMR techniques were used to determine the identities of 3 and 4 as the new compounds cripowellin C and D. A fifth compound was identified as the known alkaloid hippadine, which was inactive against Plasmodium falciparum. The antiplasmodial IC₅₀ values of compounds 1–4 were determined to be 30 ± 2, 180 ± 20, 26 ± 2, and 260 ± 20 nM, respectively, and their antiproliferative IC₅₀ values against the A2780 human ovarian cancer cell line were 11.1 ± 0.4, 16.4 ± 0.1, 25 ± 2, and 28 ± 1 nM.     

Investigations on the lectin-producing cells in the sponge Axinella polypoides (Schmidt)

Summary The localization of two carbohydrate binding proteins, so-called lectins, was studied in the sponge tissue of Axinella polypoides by light and immunofluorescence microscopy. They do not occur at the cellular surface of any cell type, but they are stored in vesicles of the spherulous cells. After short formaldehyde fixation spherulous cells can be isolated and they release the active lectins upon lysis in distilled water.Electron microscopical studies of spherulous cells show that they contain almost nothing else but a small nucleus and vesicles of different size and number. Small vesicles are full of an electron dense material, whereas the content of large vesicles has a fluffy and fibrillar structure. Spherulous cells are large and tightly packed in the outer layer of the ectosome and in the mesh work of the spongin fibres of the central axis. They are small and scattered in the inner layer of the ectosome, and they are found throughout the choanosome. The function of the lectins is not clearly defined, and different alternatives such as participation in glycoprotein synthesis, immunological defense, or carbohydrate transport are possible.This study was supported by a grant from the Deutsche ForschungsgemeinschaftWe are gratefully indebted to Dr. D. Keyser for his help in our electron microscopical studies     

ACL-I, a lectin from the marine sponge Axinella corrugata: isolation, characterization and chemotactic activity

The lectin from the marine sponge Axinella corrugata (ACL-I) was purified by affinity chromatography on rabbit erythrocytic stroma incorporated into a polyacrylamide gel followed by gel filtration on Ultrogel AcA 44 column. Purified ACL-I is a hexameric glycoprotein with a Mr of 82.3 kDa estimated by SDS-PAGE and 78.5 kDa by FPLC on Superose 12 HR column. The pI of lectin is 6.3 and ACL-I is constituted of 13.9 kDa similar subunits some of them linked by disulphide bridges. This lectin agglutinates native rabbit, goat and dog erythrocytes and in less extent human erythrocytes. The hemagglutinating activity is independent of Ca(2+), Mg(2+) and Mn(2+), but it is strongly inhibited by carbohydrates containing N-acetyl groups. ACL-I is stable up to 70 degrees C for 30 min, with optimum pH between 7 and 8, and it is also resistant to enzymatic proteolysis in vitro. In the presence of reducing or denaturant agents, the lectin activity decreases. ACL-I displays chemotactic effect on rat neutrophil in vitro which is inhibited by N-acetyl-d-glucosamine.     

Novel triterpene glycosides from the sponge Ulosa sp

New triterpene glycosides, ulososides C, (20S,22S,23R,24S)-3 beta,22, 23-trihydroxy-3-O-(beta-D-glucopyranosyl)-32-nor-24-methyllanost- 8(9)-ene-30-oic acid, D, (20S,22S,23R,24S)-3 beta,22, 23-trihydroxy-3-O-(beta-D-N-acetyl-glucosaminopyranosyl)-32-nor- 24-methyllanost-8(9)-ene-30-oic acid, and E, (20S,22S,23R,24S)-3 beta,22, 23-trihydroxy-3-O-(beta-D-glucuronopyranosyl-(1-->2)-alpha-D- arabinopyranosyl-32-nor-24-methyllanost-8(9)-ene-30-oic acid, were isolated from an Ulosa sp. sponge. Their structures were determined by spectral methods and chemical transformations. Specific features of their structures are discussed.     

Biological activities of ACL-I and physicochemical properties of ACL-II, lectins isolated from the marine sponge Axinella corrugata

Lectin II from the marine sponge Axinella corrugata (ACL-II) was purified by affinity chromatography on rabbit erythrocytic stroma incorporated into a polyacrylamide gel, followed by gel filtration on Ultrogel AcA 44 column. Purified ACL-II is a lectin with an Mr of 80 kDa and 78 kDa, estimated by SDS-PAGE and by FPLC on Superose 12 HR column, respectively. ACL-II mainly agglutinates native rabbit erythrocytes and this hemagglutinating activity is independent of Ca^2 +, Mg^2 + and Mn^2 +, but is inhibited by d-galactose, chitin and N-acetyl derivatives, with the exception of GalNAc. ACL-II is stable for up to 65 °C for 30 min, with a better stability at a pH range of 2 to 6. In contrast, ACL-I displays a strong mitogenic and cytotoxic effect.     

Three new 7-keto sterols from the Mediterranean sponge Clathrina clathrus

The CHCl3 extract of the Mediterranean sponge Clathrina clathrus was shown to contain three new sterols: (22 E)-3 beta-hydroxycholesta-5,8,22-trien-7-one (1), (22 E, 24 xi)-3 beta-hydroxy-24-methylcholesta-5,8,22-trien-7-one (2), and (22 E, 24 xi)-3 beta-hydroxy-24-ethylcholesta-5,8,22-trien-7-one (3), whose structures were elucidated on the basis of physico-chemical evidence.     

Novel bioactive compound from the Sparassis crispa mushroom

A novel compound (2) and a known one (1) were isolated from the mushroom, Sparassis crispa. Both compounds inhibited melanin synthesis and MRSA growth.     

Novel alkaloids from the roots of Stemona sessilifolia

Four new Stemona alkaloids, sessilistemonamines A-C (1-3, resp.) and dihydrostemoninine (4), were isolated from the roots of Stemona sessilifolia. Their structures and relative configurations were elucidated by means of in-depth 1D- and 2D-NMR-spectroscopic as well as mass-spectrometric experiments; and the structure of 4 was solved by X-ray single-crystal diffraction. The stereoisomeric compounds 1-3 share an unprecedented tetracyclic decahydro-1H-furo[2',3':4,5]cyclopenta[1,2-b]pyrrolo[1,2-a]azepine nucleus. Compounds 1 and 2 were found to be moderately active in terms of acetylcholinesterase (AchE) inhibition, with IC50 values of 68.8+/-9.5 and 17.1+/-2.5 microM, resp.     

Novel terpenoids of the fungus Aspergillus insuetus isolated from the Mediterranean sponge Psammocinia sp. collected along the coast of Israel

Three novel meroterpenoids, insuetolides A-C (1-3) and four drimane sesquiterpenes, the new (E)-6-(4'-hydroxy-2'-butenoyl)-strobilactone A (4) and the known 2α, 9α, 11-trihydroxy-6-oxodrim-7-ene (5), strobilactone A (6) and (E,E)-6-(6',7'-dihydroxy-2',4'-octadienoyl)-strobilactone A (7), were isolated from the EtOAc extract of the culture medium of the marine-derived fungus Aspergillus insuetus (OY-207), which was isolated from the Mediterranean sponge Psammocinia sp. The structures of the compounds were determined by spectroscopic methods. Insuetolides A-C reveal a new carbon skeleton derived from the cyclization of farnesyl and 3, 5-dimethylorsellinic acid. Compounds 1, 6, and 7 exhibited anti-fungal activity towards Neurospora crassa with MIC values of 140, 242, and 162 μM, respectively; and compounds 3, 4, and 7 exhibited mild cytotoxicity towards MOLT-4 human leukemia cells.     

Novel polyhydroxysterols from the Red Sea marine sponge Lamellodysidea herbacea

Chemical investigation of the dichloromethane extract of the Red Sea marine sponge Lamellodysidea herbacea led to the isolation of four novel polyhydroxysteroids: cholesta-8-en-3beta,5alpha,6alpha,25-tetrol (1), cholesta-8(14)-en-3beta,5alpha,6alpha,25-tetrol (2), cholesta-8,24-dien-3beta,5alpha,6alpha-triol (3), and cholesta-8(14),24-dien-3beta,5alpha,6alpha-triol (4). Their structures were identified through 1D and 2D NMR studies. Relative stereochemistries were established by analysis of chemical shifts, coupling constants, and NOESY correlations. Compounds 3-4 showed antifungal activity against Candida tropicalis, with an inhibition diameter of 13 and 11 mm at 10 microg/disc, respectively.