Natalia K. Utkina

Cyclosmenospongine, a new sesquiterpenoid aminoquinone from an Australian marine sponge Spongia sp.

A new sesquiterpenoid aminoquinone, cyclosmenospongine (1), containing a dihydropyran ring, was isolated from an Australian marine sponge Spongia sp., along with the known metabolites, smenospongiarine, ilimaquinone and smenospongine. The structure of 1 was determined from spectroscopic data.

Sesquiterpenoid aminoquinones from the marine sponge Dysidea sp.

Four new sesquiterpenoid arenarone derivatives, 18-aminoarenarone (1), 19-aminoarenarone (2), 18-methylaminoarenarone (3), and 19-methylaminoarenarone (4), and the new dimeric popolohuanone F (5), a derivative of 19-aminoarenarone (2) and arenarol (6), have been isolated from the Australian marine sponge Dysidea sp. together with the known compounds arenarol (6) and popolohuanone A (7). The structures of the new compounds 1-5 were established from extensive NMR spectroscopic data. Popolohuanones A (7) and F (5) and arenarol (6) showed DPPH radical scavenging activity with IC(50) values of 35, 35, and 19 microM, respectively.

Antioxidant activity of phenolic metabolites from marine sponges

The marine-sponge metabolitesilimaquinone (1), isospongiaquinone(2),puupenone(3), 15-methoxypuupenol (4), 2-methyl-2-pentaprenyl-6-hydroxychromene (5), (+)-curcuphenol (6), (+)-curcudiol (7), and semisynthetic sesquiterpenequinones (8-11) were investigated for ability to trap the free radical 1,1,-diphenyl-2-picrylhydrazyl (DPPH), to inhibit Fe2+ /ascorbate-induced oxidation of lipidsfromrat-brain homogenate, and to inhibit oxidation of linseed oil. It was shown that metabolites 3-5 were the most active antioxidants.

Marine natural products acting on the acetylcholine-binding protein and nicotinic receptors: from computer modeling to binding studies and electrophysiology.

For a small library of natural products from marine sponges and ascidians, in silico docking to the Lymnaea stagnalis acetylcholine-binding protein (AChBP), a model for the ligand-binding domains of nicotinic acetylcholine receptors (nAChRs), was carried out and the possibility of complex formation was revealed. It was further experimentally confirmed via competition with radioiodinated α-bungarotoxin ([125I]-αBgt) for binding to AChBP of the majority of analyzed compounds. Alkaloids pibocin, varacin and makaluvamines С and G had relatively high affinities (Ki 0.5–1.3 μM). With the muscle-type nAChR from Torpedo californica ray and human neuronal α7 nAChR, heterologously expressed in the GH4C1 cell line, no competition with [125I]-αBgt was detected in four compounds, while the rest showed an inhibition. Makaluvamines (Ki ~ 1.5 μM) were the most active compounds, but only makaluvamine G and crambescidine 359 revealed a weak selectivity towards muscle-type nAChR. Rhizochalin, aglycone of rhizochalin, pibocin, makaluvamine G, monanchocidin, crambescidine 359 and aaptamine showed inhibitory activities in electrophysiology experiments on the mouse muscle and human α7 nAChRs, expressed in Xenopus laevis oocytes. Thus, our results confirm the utility of the modeling studies on AChBPs in a search for natural compounds with cholinergic activity and demonstrate the presence of the latter in the analyzed marine biological sources.

Antioxidant activityofaromatic alkaloids from the marine sponges Aaptos aaptos and Hyrtios SP.

Aaptamine (1) and isoaaptamine (2) were isolated from the marine sponge Aaptos aaptos; 6-bromo-2′-de-N-methylaplysinopsin (3) from the marine sponge Hyrtios sp. Alkaloids 1–3 were tested for the ability to trap 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical, to reduce Folin–Ciocalteau reagent (FCR), and to inhibit oxidation of linoleic acid (LA) induced by peroxide radicals. Compounds 1 (IC50 18 μM), 2 (IC50 16 μM), and 3 (IC50 18 μM) reacted strongly with DPPH, comparable with trolox (IC50 16 μM) and showed high reducing ability for FCR. The inhibition of LA oxidation by 1–3 was comparable with that of ionol (BHT). It was shown that the antioxidant activity of 1–3 was related to their ability to release both electrons and H atoms.

Transformation of tricyclic makaluvamines from the marine sponge Zyzzya fuliginosa into damirones

Makaluvamines H and C isolated from the marine sponge Zyzzya fuliginosa were transformed into damirones A and B, respectively, by alkaline hydrolysis. The crystal structure of damirone A was established by X-ray diffraction analysis.

UV-stability and UV-protective activity of alkaloids from the marine sponge Zyzzya fuliginosa

Alkaloids from the marine sponge Zyzzya fuliginosa damirones A (1) and B (2); makaluvamines H (3), C (4), G (5), and L (6); and zyzzyanones A (8) and B (9) were investigated for the ability to protect egg-cell membranes of the sea urchin Strongylocentrotus nudus from UV-radiation. Damirones, zyzzyanones, and tricyclic makaluvamines C (4) and H (3) exhibited the greatest membrane-protective activity. It was shown that makaluvamines G (5) and L (6) were converted by UV-irradiation into damirones A (1), B (2), tricyclic makaluvamines H (3), C (4), and zyzzyanones A (8) and B (9), respectively.

New polybrominated diphenyl ether from the marine sponge Dysidea herbacea

Tropical marine sponges of the family Dysideidae contain a series of antimicrobial polybrominated diphenyl ethers with varying degrees of hydroxylation, methoxylation, and bromination [1]. Recently this class of metabolites has attracted attention because of their ability to inhibit 15-lipoxygenase in mammals [2] and the assembly of microtubular proteins [3] and to regulate interleukin-8 production [4]. We investigated the marine sponge Dysidea herbacea collected in the Large Barrier Reef during the ninth cruise of R/V Academic Oparin. Sponge (3 g) was lyophilized and extracted with CHCl3. The extract was repeatedly chromatographed over silica gel to produce 1 (0.9 mg), 2 (10 mg), 3 (4.5 mg), 4 (0.6 mg), 5 (0.5 mg), and 6 (0.5 mg). Compounds 2-6 were identified by comparing their spectral properties with those in the literature [5, 6]. Diphenyl ether 1, mp 181-183°C (CHCl3) was a new representative of this class.

Crystal structure of the complex of brominated diphenyl ethers from the marine spongeDysidea fragilis

The spatial structures of 2-(2′,4′-dibromophenoxy)-3,4,5-tribromophenoI (1) and 2-(2′-hydroxy-4′,6′-dibromophenoxy)-4,6-dibromoanisole (2) in crystals of the complex formed through two intermolecular O-H-O bonds were determined. The conformations of both molecules were found to be stabilized by intermolecular hydrogen bonds. The external hydrophobic surface of the complex of two molecules was shown to be occupied by nine bromine atoms.

Tetrahydroisoquinoline alkaloid N-methylnorsalsolinol from the Australian marine sponge Xestospongia SP.

The EtOH extract from the Australian marine sponge Xestospongia sp. (Order Haplosclerida) collected during the 9th cruise of RV Akademik Oparin (Bougainville Reef, Australia) was studied during a search for antioxidants in marine organisms. A lyophilized specimen of the marine sponge (100 g) was extracted exhaustively first with CHCl3 and then EtOH (50%). The aqueous EtOH extract, which exhibited high activity for trapping DPPH radicals (2,2-diphenyl-1-picrylhydrazyl), was concentrated in vacuo. The aqueous residue was extracted with EtOAc and then n-BuOH. The aqueous and BuOH fractions showed antiradical activity. They were separated at low pressure over a column of C-18 silica gel (Fluka) using a H2O:EtOH gradient. Antiradical activity was observed in the fraction eluted by H2O during the separation of the n-BuOH fraction. It was concentrated in vacuo and crystallized from aqueous EtOH to afford 1 (132.4 mg), which was active for trapping DPPH radicals. An additional amount of 1 (8 mg) was isolated in the same manner from the aqueous fraction remaining after distribution between H2O and n-BuOH. Compound 1 (140.4 mg, 0.07% per dry sponge wt.), pale-yellow crystals (H2O:EtOH), mp 270–273°C. UV spectrum (H2O, max, nm, log ): 225, 283, 385 (3.56, 3.43, 2.54). The 13C NMR spectrum of 1 contained resonances for 10 C atoms including one methyl, three methylene, two methine, and four quaternary C atoms. The PMR spectrum also showed resonances for one methyl, three methylenes, and two singlets of aromatic protons in addition to two exchangeable protons ( 9.05 and 9.09) (Table 1). The high-resolution mass spectrum (HR-EI-MS) of 1 showed a base peak for [M – H]+ at m/z 178.0867 (C10H12NO2, 100%) that was characteristic of electron-impact decomposition of 1,2,3,4-tetrahydroisoquinolines [1]. 2D NMR spectroscopy experiments (HSQC, HMBC, COSY) enabled all resonances of 1 to be assigned. Thus, 1 was identified as 2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (N-methylnorsalsolinol). A comparison of NMR spectra of 1 with those of 6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (norsalsolinol) [2] confirmed that 1 was the N-methyl derivative of norsalsolinol. The PMR and 13C NMR spectra of N-methylnorsalsolinol are given in Table 1 because these data have not been reported in the literature.