A new pentacyclic guanidine alkaloid, monanchomycalin C (1), along with the earlier known ptilomycalin A (2), were isolated from the Far-Eastern marine sponge Monanchora pulchra. The structure of 1 was elucidated using 1D and 2D NMR spectroscopic and mass spectrometric data. Compounds 1 and 2 exhibited cytotoxic activities against human breast cancer MDA-MB-231 cells with IC 50 values of 8.2 µM and 4.3 µM, respectively.

Urupocidins A and B (1 and 2), bisguanidine alkaloids with an unprecedented skeleton system, derived from polyketide precursors and containing an unusual N-alkyl-N-hydroxyguanidine moiety, have been isolated from the sponge Monanhora pulchra. The structures of 1 and 2, including absolute configuration, were established using the detailed analysis of 1D and 2D NMR, CD, and mass spectra as well as chemical transformations. Compound 1 increases nitric oxide production in murine macrophages via inducing iNOS expression.

New pentacyclic guanidine alkaloids, normonanchocidins A, B and D (1-3) along with the earlier known monanchocidin A were isolated from the Far-Eastern marine sponge Monanchora pulchra. Structures of 1-3 were elucidated using 1D-and 2D-NMR spectroscopic and mass spectrometric data. Compound 1 and a mixture of 2 and 3 (1:1) exhibited cytotoxic activities against human leukemia THP-1 cells with IC 50 values of 2.1 µM and 3.7 µM, respectively, and against cervix epithelial carcinoma HeLa cells with IC 50 of 3.8 µM and 6.8 µM, respectively.

New marine natural products, pulchranins B and C (2 and 3), were isolated from the marine sponge Monanchora pulchra and their structures were established using NMR and MS analysis. Compounds 2 and 3 were moderately active as inhibitors of TRPV1 (EC50 value of 95 and 183 μM, respectively) and less potent against TRPV3 and TRPA1 receptors.

Monanchocidin A (MonA) is a novel marine alkaloid with promising anti-cancer properties. We recently demonstrated its high efficacy in human urogenital cancers including germ cell tumors. Here, we applied a global proteome screening approach to investigate molecular targets and biological processes affected by MonA in the human cisplatin-resistant germ cell cancer cell line NCCIT-R. Bioinformatical analysis of the proteomics data predicted an effect of MonA on cancer cell migration. Thus, proteins known to be involved in cancer cell migration and invasion were chosen for further validation. The protein alterations identified by proteomics resulted from both, regulation of the total protein expression and post-transcriptional modifications. Among others, regulation of an isoform of vimentin, up-regulation of multiple apolipoprotein E isoforms, and inhibition of hypusination of eukaryotic translation initiation factor 5A-1 were found upon treatment with MonA. Further functional analyses were performed and revealed decreased cell migration and colony formation of cancer cells treated with MonA at non-cytotoxic and non-antiproliferative concentrations. This work provides further insights into the molecular mechanisms behind MonA bioactivity. Furthermore, our research is exemplary for the ability of proteomics to predict drug targets and mode of action of natural anti-cancer agents.

It was shown earlier that toxin-containing marine invertebrates, in particular sponges (phylum Porifera) and sea cucumbers (phylum Echinodermata, class Holothurioidea), often contain unusual sterols instead of cholesterol and other ' 5 -sterols, in contrast with other animals [1]. They differ from cholesterol either by the position of the double bond in the steroid core (sometimes its absence) [2][3][4] or by the presence of highly alkylated side chains [5,6]. According to a hypothesis proposed by us, the unusual sterols protect the biomembranes of toxin-producing marine invertebrates from the lytic action of their own toxins as a result of sterol-toxin biochemical coordination occurring in such instances [7].In continuation of the search for new sources of biologically active compounds among invertebrates of Far-East seas, we recently found that EtOH extracts of the sponge Monanchora pulchra exhibited high cytotoxic activity. It was shown that this sponge contained a new cytotoxic polycyclic guanidine alkaloid that we called monanchocidin [8]. We investigated the sterol fraction from this sponge collected near the shores of Urup Is. (Kuril Islands, 46°07.0 N, 150°02 E) in August 2008 in order to test further this hypothesis.The sponge for chemical investigation was stored at -20°C. Thawed ground biological material (18.9 g dry wt.) was extracted (3u) with EtOH. The combined extracts were concentrated to dryness in vacuo and distributed between H 2 O and BuOH. The evaporated BuOH layer (2.14 g) was dissolved in EtOH (90%) and extracted (3u) with hexane. The combined hexane layers were concentrated to afford total nonpolar substances (0.69 g). A part (0.215 g) of this total was chromatographed over a column of silica gel (KSK, 50-160 Pm) using a hexaneoEtOAc gradient (4:1) to afford the total sterol fraction (57 mg, 0.92% of dry wt) that was separated using HPLC into three subfractions consisting of ' 5 -(1.3 mg) and ' 7 -sterols (24.3 mg), and stanols (21 mg). These were analyzed using PMR as described before [2,3,9,10].The structures of the free sterols as the acetylated derivatives were identified using GC and comparison with the relative retention times (RRT) of standard sterols and using GC-MS as before [2,3,9,10]. Table 1 presents the results. Table 1 shows that the sterol fraction from the studied sponge contained 29 previously known C 26 , C 27 , C 28 , C 29 , and C 30 compounds that had double bonds in the ' 7 , ' 7,22 , ' 7,24(28) , ' 0 , ' 22 , ' 5 , ' 5,22 , and ' 5,24(28) positions. Sterols of the ' 7 series were basic and made up 52.1% of the total sterol fraction. The stanol content was 45.1% whereas ' 5 -sterols were a minor fraction with a content of 2.8%. The principal components of the fraction were identified as 5-D-cholestan-3E-ol and 5D-cholest-7-en-3E-ol. Thus, yet another instance of toxin-(unusual sterols) biochemical coordination was found.

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