[reaction: see text] The novel antifungal compound oceanalin A, an unprecedented "hybrid sphingolipid", was isolated from the marine sponge Oceanapia sp. The structure was elucidated using NMR and MS spectral analysis and chemical degradation. Oceanalin A exhibits in vitro antifungal activity against Candida glabrata with an MIC of 30 mug/mL.

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Rhizochalin A (4), the fourth representative of two-headed glycosphingolipids, was isolated as its peracetate from the sponge Rhizochalina incrustata. Its structure has been established as the 2-ethyl carbamoate of rhizochalin on the basis of spectroscopic data and chemical transformations.

A new fatty acid, (5Z,9Z)-22-methyl-5,9-tetracosadienoic acid (1a), and a rare fatty acid, (5Z,9Z)-23-methyl-5,9-tetracosadienoic acid (2a), the predominant constituents of the free fatty acid fraction from the lipids of the sponge Geodinella robusta, were isolated and partly separated by reversed phase high-performance liquid chromatography, followed by multifold crystallization from MeOH to give 1a and 2a in 70% and 60% purity, respectively. These fatty acids were identified as (5Z,9Z)-22- and (5Z,9Z)-23-methyl-5,9-tetracosadienoic acids by nuclear magnetic resonance techniques, including distortionless enhancement by polarization transfer, heteronuclear multiple quantum connectivity, and correlation spectroscopy experiments, as well as from mass-spectrometric data for their methyl esters, the methyl esters of their perhydro derivatives, and their pyrrolidides. Mixtures of 1a and 2a showed cytotoxic activity against mouse Ehrlich carcinoma cells and a hemolytic effect on mouse erythrocytes. The sterol fraction from the same sponge was analyzed by gas-liquid chromatography-mass spectrometry, and 24-methylenecholesterol was identified as a main constituent of this fraction. The implications of the co-occurrence of membranolytic long-chain fatty acids and 24-methylenecholesterol as a main membrane sterol are discussed in terms of the phenomenon of biochemical coordination.

Nine new cerebrosides 1a-d, 2a, 2b, 3a-c were found in the extract of a Far-Eastern glass sponge Aulosaccus sp. (class Hexactinellida). These β-D-glucopyranosyl-(1 → 1)-ceramides contain sphingoid bases (2S,3S,4R,11Z)-2-aminoeicos-11-ene-1,3,4-triol (in 1a-d), (2S,3S,4R,13Z)-2-aminoeicos-13-ene-1,3,4-triol (in 2a, b) and (2S,3S,4R,13S*,14R*)-2-amino-13,14-methylene-eicosane-1,3,4-triol (in 3a-c), which are N-acylated by (2R,15Z)-2-hydroxydocos-15-enoic (in 1a, 2a, 3a), (2R,16Z)-2-hydroxytricos-16-enoic (in 1b, 2b, 3b), (2R,17Z)-2-hydroxytetracos-17-enoic (in 1d) and (2R)-2-hydroxydocosanoic (in 1c, 3c) acids. The monoenoic and cyclopropane-containing sphingoid bases of compounds 1a-d, 2a, 2b, 3a-c have not been found previously in any sphingolipids. The structures of the cerebrosides were elucidated on the basis of (1)H-, (13)C-NMR spectroscopy, mass spectrometry, optical rotation data and chemical transformations. A simplified method for the assignment of the absolute configuration of 2-hydroxy fatty acids by GC analysis of their (2R)- and (2S)-oct-2-yl esters was proposed.

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.

Three new sesterterpene sulfates, halisulfates 8-10 (1-3), were isolated from the Australian sponge Darwinella australensis. The structures of these compounds were determined by combined spectroscopic methods. The stereochemistry of the decalin moiety was assigned on the basis of NMR interpretations. Halisulfates 9 and 10 inhibited cell division of sea urchin eggs in moderate concentration.

Twenty nine 3,5 dibromotyrosine derivatives were isolated from the ethanol extract of the marine sponge Aplysina sp. (South China Sea) including the earlier unknown compounds, in particular, p hydroxycyclohexadienone and p hydroxycyclohexenone ketals. The isolated enones, dienones, and ketals can be transformation products of aeroplysinin 1 in the course of its reactions with water and alcohols.