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Four bicyclic and three pentacyclic guanidine alkaloids (1-7) were isolated from a French Polynesian Monanchora n. sp. sponge, along with the known alkaloids monalidine A (8), enantiomers 9-11 of known natural product crambescins, and the known crambescidins 12-15. Structures were assigned by spectroscopic data interpretation. The relative and absolute configurations of the alkaloids were established by analysis of H-1 NMR and NOESY spectra and by circular dichroism analysis. The new norcrambescidic acid (7) corresponds to interesting biosynthetic variation within the pentacyclic core. All compounds exhibited antiproliferative and cytotoxic efficacy against KB, HCT116, HL60, MRCS, and B16F10 cancer cells, with IC50 values ranging from 4 nM to 10 mu M.

Highly biologically active marine sesquiterpene ilimaquinone was selected for chemical modifications. Its biotransformation was investigated using a combinatorial approach as an original way to screen different strains of microorganisms. Mucor circinelloides ATCC 8541 was able to structurally modify ilimaquinone into three different compounds. A stereospecific epoxidation was observed and compared to chemical epoxidation. A hydroxylation of the decalin ring was also observed as well as an unexpected substitution on the quinone ring by ethanolamine. Compounds were evaluated against several cell lines.

Stalked crinoids were, for a long time, known as fossils found in different quarries, and also from ocean depths since the great expeditions of the eighteenth century. The chemical analyses of fossils and also of living organisms led to the discovery of new bioactive pigments, and also confirmed that the core structures of these pigments had been preserved during the fossilization process. The existence of these quinoid pigments also leads to several interesting questions related to their stereochemistry and the photoactivation of their bioactivity.

Développer l’utilisation durable des substances naturelles, faire de la protection de la biodiversité une activité rentable pour mieux la promouvoir tout en favorisant le développement des territoires concernés : il y a là, dans le contexte actuel, des enjeux importants pour la Polynésie française. En effet, la Polynésie française bénéficie d’un potentiel intéressant par sa diversité (marine et terrestre) et ses spécificités, liées notamment à l’insularité. C’est ce qu’atteste le succès de quelques-uns de ses produits mondialement connus : perles, monoï, jus de nono, vanille. Mais la mise en valeur de ce potentiel demeure encore limitée ; son inventaire lui-même reste très partiel. Pour en préciser les dimensions réelles, cette expertise collégiale s’est attachée à évaluer scientifiquement la ressource, tout en mettant en évidence les substances d’intérêt et les orientations de recherche prioritaires. Les conditions socio-économiques, juridiques et techniques de la mise en valeur de cette ressource sont analysées ici aux fins de fournir des éléments de connaissance et des recommandations utiles à la définition par la Polynésie d’une politique originale de valorisation de ses substances naturelles. A major challenge for French Polynesia in the present situation is to develop sustainable use of natural substances, make the protection of biodiversity a profitable activity to better promote it, while at the same time furthering the development of the territories concerned. French Polynesia possesses a wide diversity of marine and terrestrial species, largely because the territory consists of many scattered islands. Such diversity represents a valuable potential, as illustrated by the success of such world-famous products as Polynesian pearls and vanilla, monoi and noni juice. However, the potential has not so far been exploited to any great extent, and has not even been fully catalogued. This expert group review was designed to discover the extent of the potential, make a scientific assessment of the resource, pinpoint substances with economic potential and indicate priority directions for research. It also includes analysis of the socio-economic, legal and technical conditions for their utilisation. This purpose of the review is to supply useful facts and make recommendations for defining an original policy for French Polynesia’s economic use of natural substances.

Glycolipids of Myrmekioderma sponges contain Myrmekiosides, a new family of glycolipids with a unique structure of mono-O-alkyl-diglycosylglycerols. This report deals with the identification and biological activity of the new Myrmekioside E from Myrmekioderma dendyi. Its structure has been elucidated from spectroscopic data and chemical degradation studies. It contained a glycerol backbone linked to xylose and N-acetylglucosamine, and an alkyl long-chain with a terminal alcohol group. A related glycolipid, Trikentroside, known in the sponge Trikentrion laeve, was subjected to a comparative biological evaluation. Both glycolipids inhibit proliferation of two human non-small cell lung cancer cell lines (NSCLC-N6 and A549).

Four samples of Suberea ianthelliformis were investigated and furnished five new and 13 known brominated tyrosine-derived compounds. Two of the new compounds were identified as araplysillin N20-formamide and its N-oxide derivative. Three other new compounds, araplysillins IV, V, and VI, were isolated and identified as analogs of araplysillin II. Most of these compounds exhibit moderate inhibitory activities against chloroquine-resistant and -sensitive strains of Plasmodium falciparum, and were investigated for their PFTase inhibitory properties. The chemical content of the investigated sponges is correlated with their molecular phylogeny.

In our investigation of bioactive marine natural products, we revisited an ethanolic extract of the New Caledonian sponge Cymbastela cantharella. Four new natural compounds (3-6) were isolated and their structural determinations as dihydrohymenialdisine derivatives were achieved by spectral data analysis and chemical conversion. These products did not show any activity in the Polo Like kinase bioassay, demonstrating thus the importance of the unique structure of hymenialdisine, known as an improved kinase inhibitor.

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International audience

Bacteria were thought to be devoid of tyrosine-phosphorylating enzymes. However, several tyrosine kinases without similarity to their eukaryotic counterparts have recently been identified in bacteria. They are involved in many physiological processes, but their accurate functions remain poorly understood due to slow progress in their structural characterization. They have been best characterized as copolymerases involved in the synthesis and export of extracellular polysaccharides. These compounds play critical roles in the virulence of pathogenic bacteria, and bacterial tyrosine kinases can thus be considered as potential therapeutic targets. Here, we present the crystal structures of the phosphorylated and unphosphorylated states of the tyrosine kinase CapB from the human pathogen Staphylococcus aureus together with the activator domain of its cognate transmembrane modulator CapA. This first high-resolution structure of a bacterial tyrosine kinase reveals a 230-kDa ring-shaped octamer that dissociates upon intermolecular autophosphorylation. These observations provide a molecular basis for the regulation mechanism of the bacterial tyrosine kinases and give insights into their copolymerase function., Author Summary An idiosyncratic new class of bacterial enzymes, bacterial tyrosine-kinases (BY-kinases), has been characterized. These enzymes, which are involved in an increasing number of physiological processes ranging from stress resistance to pathogenicity, share no sequence similarities with eukaryotic kinases, and their function remains largely unknown. They have nevertheless been described to undergo autophosphorylation on a C-terminal tyrosine cluster and to phosphorylate endogenous protein substrates. We describe here the first crystal structure of a bacterial tyrosine kinase, namely CapB from the pathogen Staphylococcus aureus, in complex with the cytoplasmic domain of the transmembrane stimulatory protein CapA. Our data explain the activation mechanism of CapB by CapA and allow us to propose a regulatory mechanism based on intermolecular autophosphorylation. These results also give new insights onto the phosphorylation of the endogenous substrate CapO, an enzyme involved in the synthesis of polysaccharide precursors. CapA and CapB, among others, are involved as copolymerases in the synthesis of extracellular polysaccharides that are thought to be potent virulence factors. Thus, these structural data provide the basis for designing specific inhibitors for these enzymes, which constitute an original and attractive target for the development of new drugs to treat infectious diseases., Structural analysis of a conserved bacterial tyrosine kinase fromStaphylococcus aureus provides the basis for deciphering its regulatory mechanism, leading to a model for its implication in extracellular polysaccharide synthesis.

Reported here is the first polyarsenic compound ever found in nature. Denominated arsenicin A, it was isolated along a bioassay-guided fractionation of the organic extract of the poecilosclerid sponge Echinochalina bargibanti collected from the northeastern coast of New Caledonia. In defining an adamantine-type polyarsenic structure for this compound, deceptively simple NMR spectra were complemented by extensive mass spectral analysis. However, it was only the synthesis of a model compound that provided the basis to discriminate structure 4 from other spectrally compatible structures for arsenicin A; to this end, a comparative ab initio simulation of IR spectra for the natural and the synthetic compounds was decisive. Arsenicin A is endowed with potent bactericidal and fungicidal activities on human pathogenic strains. All this may revive pharmacological interest in arsenic compounds while prompting us to rethink the arsenic cycle in nature.

Lors de cette conférence, nous présentons les résultats les plus récents obtenus en collaboration avec l'ORSTOM et le CNRS, dans le cadre du programme SMIB; en particulier quelques aspects de la chimie de quatre organismes marins récoltés au large de la Nouvelle Calédonie sont discutés : #Gymnocrinus richeri$, un crinoïde fossile vivant découvert par Bertrand Richer de Forges à 520 m de profondeur; l'étoile de mer #Tremaster novaecaledoniae$, aussi un fossile vivant, récolté à 530 m; deux éponges profondes, #Erylus sp.$ et #Jereicopsis graphidiophora$, cette dernière étant d'un nouveau genre découvert par Claude Lévi du Muséum National d'Histoire Naturelle de Paris. (Résumé d'auteur)

Boophilus microplus$ est responsable de diminution de poids, voire dans certains cas de la perte de bovidés, de même cet ectoparasite peut être vecteur de maladies. En Nouvelle Calédonie comme dans la plupart des pays, le contrôle de #B. microplus$ est assuré par des baignades régulières dans des bains acaricides. En Nouvelle Calédonie le premier cas de résistance est apparu en 1981 (Brun et al. 1983). Au cours des trois dernières années l'activité acaricide de 150 organismes marins a été évaluée dans le cadre du programme SMIB (Substances Naturelles d'Intérêt Biologique). Les échantillons ont été récoltés à l'intérieur du lagon et à l'extérieur, entre 300 et 700 mètres de profondeur. Une méthode simple, dérivée de celle de Stone et Haydock (1962) a été utilisée pour tester l'activité acaricide des organismes lyophilisés sur de jeunes larves de tique du bétail. La plupart des produits actifs ont été trouvés parmi les éponges et les gorgones. (Résumé d'auteur)

Deux composés antibiotiques et cytotoxiques dénommés phloeodictine et thiophloeodictine ont été isolés de l'éponge d'eau profonde #Phloeodictyon$ sp. originaire de Nouvelle Calédonie. Leurs structures ont été établies par une étude spectroscopique approfondie incluant les RMN 1D et 2D (HMQC, DQF-COSY, HOHAHA et HMBC). (Résumé d'auteur)