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A Tetraselmis sp. was selected for its antioxidant activity owing to its high lipid peroxidation inhibition capacity. With the aim to monitor culture conditions to improve antioxidant activity, effects of CO2-induced acidification on Tetraselmis growth, elemental composition, photosynthetic parameters and antioxidant activity were determined. Two pH values were tested (6.5 and 8.5) in batch and continuous cultures in photobioreactors. Acidification enhanced cell growth under both culture methods. However, the microalgae physiological state was healthier at pH 8.5 than at pH 6.5. Indeed, photosynthetic parameters measured with pulse amplitude modulated (PAM) fluorometry showed a decrease in the photosystem II (PSII) efficiency at pH 6.5 in batch culture. Yet, with the exception of the PSII recovering capacity, photosynthetic parameters were similar in continuous culture at both pH. These results suggest that lowering pH through CO2-induced acidification may induce a lower conversion of light to chemical energy especially when coupled with N-limitation and/or under un-balanced culture conditions. The highest antioxidant activity was measured in continuous culture at pH 6.5 with an IC50 of 3.44 ± 0.6 μg mL−1, which is close to the IC50 of reference compounds (trolox and α-tocopherol). In addition, the principal component analysis revealed a strong link between the antioxidant activity and the culture method, the photophysiological state and the nitrogen cell quota and C:N ratio of Tetraselmis sp.. These results highlight Tetraselmis sp. as a species of interest for natural antioxidant production and the potential of PAM fluorometry to monitor culture for production of biomass with a high antioxidant activity.

A series of 2-aryl-3-azolyl-1-indolyl-propan-2-ols was designed as new analogs of fluconazole (FLC) by replacing one of its two triazole moieties by an indole scaffold. Two different chemical approaches were then developed. The first one, in seven steps, involved the synthesis of the key intermediate 1-(1H-benzotriazol-1-yl)methyl-1H-indole and the final opening of oxiranes by imidazole or 1H-1,2,4-triazole. The second route allowed access to the target compounds in only three steps, this time with the ring opening by indole and analogs. Twenty azole derivatives were tested against Candida albicans and other Candida species. The enantiomers of the best anti-Candida compound, 2-(2,4-dichlorophenyl)-3-(1H-indol-1-yl)-1-(1H-1,2,4-triazol-1-yl)-propan-2-ol (8g), were analyzed by X-ray diffraction to determine their absolute configuration. The (&minus, )-8g enantiomer (Minimum inhibitory concentration (MIC) = IC80 = 0.000256 &micro, g/mL on C. albicans CA98001) was found with the S-absolute configuration. In contrast the (+)-8g enantiomer was found with the R-absolute configuration (MIC = 0.023 &micro, g/mL on C. albicans CA98001). By comparison, the MIC value for FLC was determined as 0.020 &micro, g/mL for the same clinical isolate. Additionally, molecular docking calculations and molecular dynamics simulations were carried out using a crystal structure of Candida albicans lanosterol 14&alpha, demethylase (CaCYP51). The (&minus, )-(S)-8g enantiomer aligned with the positioning of posaconazole within both the heme and access channel binding sites, which was consistent with its biological results. All target compounds have been also studied against human fetal lung fibroblast (MRC-5) cells. Finally, the selectivity of four compounds on a panel of human P450-dependent enzymes (CYP19, CYP17, CYP26A1, CYP11B1, and CYP11B2) was investigated.

Twelve microalgae species isolated in tropical lagoons of New Caledonia were screened as a new source of antioxidants. Microalgae were cultivated at two light intensities to investigate their influence on antioxidant capacity. To assess antioxidant property of microalgae extracts, four assays with different modes of action were used: 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2&rsquo, azino-bis (3-&eacute, thylbenzothiazoline-6-sulphonique) (ABTS), oxygen radical absorbance capacity (ORAC), and thiobabituric acid reactive substances (TBARS). This screening was coupled to pigment analysis to link antioxidant activity and carotenoid content. The results showed that none of the microalgae studied can scavenge DPPH and ABTS radicals, but Chaetoceros sp., Nephroselmis sp., and Nitzschia A sp. have the capacity to scavenge peroxyl radical (ORAC) and Tetraselmis sp., Nitzschia A sp., and Nephroselmis sp. can inhibit lipid peroxidation (TBARS). Carotenoid composition is typical of the studied microalgae and highlight the siphonaxanthin, detected in Nephroselmis sp., as a pigment of interest. It was found that xanthophylls were the major contributors to the peroxyl radical scavenging capacity measured with ORAC assay, but there was no link between carotenoids and inhibition of lipid peroxidation measured with TBARS assay. In addition, the results showed that light intensity has a strong influence on antioxidant capacity of microalgae: Overall, antioxidant activities measured with ORAC assay are better in high light intensity whereas antioxidant activities measured with TBARS assay are better in low light intensity. It suggests that different antioxidant compounds production is related to light intensity.

Nephroselmis sp. was previously identified as a species of interest for its antioxidant properties owing to its high carotenoid content. In addition, nitrogen availability can impact biomass and specific metabolites&rsquo, production of microalgae. To optimize parameters of antioxidant production, Nephroselmis sp. was cultivated in batch and continuous culture conditions in stirred closed photobioreactors under different nitrogen conditions (N-repletion, N-limitation, and N-starvation). The aim was to determine the influence of nitrogen availability on the peroxyl radical scavenging activity (oxygen radical absorbance capacity (ORAC) assay) and carotenoid content of Nephroselmis sp. Pigment analysis revealed a specific and unusual photosynthetic system with siphonaxanthin-type light harvesting complexes found in primitive green algae, but also high lutein content and xanthophyll cycle pigments (i.e., violaxanthin, antheraxanthin, and zeaxanthin), as observed in most advanced chlorophytes. The results indicated that N-replete conditions enhance carotenoid biosynthesis, which would correspond to a higher antioxidant capacity measured in Nephroselmis sp. Indeed, peroxyl radical scavenging activity and total carotenoids were higher under N-replete conditions and decreased sharply under N-limitation or starvation conditions. Considering individual carotenoids, siphonaxanthin, neoxanthin, xanthophyll cycle pigments, and lycopene followed the same trend as total carotenoids, while &beta, carotene and lutein stayed stable regardless of the nitrogen availability. Carotenoid productivities were also higher under N-replete treatment. The peroxyl radical scavenging activity measured with ORAC assay (63.6 to 154.9 &micro, mol TE g&minus, 1 DW) and the lutein content (5.22 to 7.97 mg g&minus, 1 DW) were within the upper ranges of values reported previously for other microalgae. Furthermore, contents of siphonaxanthin ere 6 to 20% higher than in previous identified sources (siphonous green algae). These results highlight the potential of Nephroselmis sp. as a source of natural antioxidant and as a pigment of interest.

The demand for natural products isolated from microalgae has increased over the last decade and has drawn the attention from the food, cosmetic and nutraceutical industries. Among these natural products, the demand for natural antioxidants as an alternative to synthetic antioxidants has increased. In addition, microalgae combine several advantages for the development of biotechnological applications: high biodiversity, photosynthetic yield, growth, productivity and a metabolic plasticity that can be orientated using culture conditions. Regarding the wide diversity of antioxidant compounds and mode of action combined with the diversity of reactive oxygen species (ROS), this review covers a brief presentation of antioxidant molecules with their role and mode of action, to summarize and evaluate common and recent assays used to assess antioxidant activity of microalgae. The aim is to improve our ability to choose the right assay to assess microalgae antioxidant activity regarding the antioxidant molecules studied.

BackgroundDifferent parts of the treeCalophyllum inophyllumL. (nuts, leaves, roots, bark, fruits, nut oil and resin) are used as traditional medicines and cosmetics in most of the Pacific Islands. The oil efficiency as a natural cure and in traditional cosmetics has been largely described throughout the South Pacific, which led us to investigateC. inophyllum’s chemical and genetic diversity. A correlative study of the nut resin and leaf DNA from three distinct archipelagos in the South Pacific was carried out in order to identify diversity patterns inC. inophyllumacross the South Pacific.MethodsCalophyllum inophyllumplants were sampled from French Polynesia, New Caledonia and Fiji. We extracted tamanu oil (nut oil) resin for chemo-diversity studies and sampled leaf tissues for genetic studies. We applied an analysis method designed for small quantities (at a microscale level), and used High Performance Liquid Chromatography (HPLC) to establish the chemo-diversity of tamanu oil resin. In-house standards were co-eluted for qualitative determination. Genetic diversity was assessed using chloroplast barcoding markers (the Acetyl-CoA carboxylase (accD) gene and the psaA-ycf3 intergenic spacer region).ResultsOur HPLC analysis revealed 11 previously known tamanu oil constituents, with variability among plant samples. We also isolated and characterized two new neoflavonoids from tamanu oil resin namely, tamanolide E1 and E2 which are diastereoisomers. Although genetic analysis revealed low genetic variation, our multivariate analysis (PCA) of the tamanu oil resin chemical profiles revealed differentiation among geographic regions.ConclusionWe showed here that chromatographic analysis using formalized in-house standards of oil resin compounds for co-elution studies against oil resin samples could identify patterns of variation among samples ofC. inophyllum,and discriminate samples from different geographical origins.

Volatile components of seven Frullania species (Frullaniaceae) from New Caledonia, including five endemic species ( F. bella, F. scalaris, F. mammillosa, F. cornuta and F. falsicornuta), were analyzed by GC-MS in order to index these plants to known chemotypes. Constituents detected in these Frullania species were mainly sesquiterpenes, as well as the bibenzyl dihydrognetin, and the flavonoid naringinin-5,7,4'-trimethyl ether. These compositions allowed an indexation of Frullania species from New Caledonia to cyclocolorenone, sesquiterpene lactone and bibenzyl chemotypes. In addition, qualitative intraspecies variations of chemical composition were very important and made indexation to known chemotypes very tricky. Moreover, two of the endemic liverworts did not possess any biomarker that linked to a known chemotype.

Plant secondary metabolites can be useful chemosystematic markers to distinguish species at different taxonomy levels. For example, sesquiterpenes and diterpenes show specific distribution patterns within conifers and so provide especially precious information about the diversity and evolutionary relationships of this group. The aim of the present study was to provide a first insight into the terpene diversity of endemic Podocarpaceae from New Caledonia. The leaf essential oils of Dacrydium araucarioides Brongn. & Gris, Dacrydium balansae Brongn. & Gris, Dacrydium guillauminii J.Buchholz, Dacrydium lycopodioides Brongn. & Gris, Falcatifolium taxoides (Brongn. & Gris) de Laub., and Acmopyle pancheri (Brongn. & Gris) Pilg. from New Caledonia were characterized by GC/FID and GC/MS analyses, and the chemotaxonomic relationships of these species were determined by comparison of their terpene compositions. Cluster analysis based on the biosynthetic origin of their volatile terpenes led to the description of three distinct groups of essential oils and showed close relationships between those of D. araucarioides and D. balansae as well as between those of A. pancheri and F. taxoides.

International audience; Volatile components of seven species of the Bazzanioideae sub-family (Lepidoziaceae) native to New Caledonia, including three endemic species (Bazzania marginata, Acromastigum caledonicum and A. tenax), were analyzed by GC-FID-MS in order to index these plants to known or new chemotypes. Detected volatile constituents in studied species were constituted mainly by sesquiterpene, as well as diterpene compounds. All so-established compositions cannot successfully index some of them to known chemotypes but afforded the discovery of new chemotypes such as cuparane/fusicoccane. The major component of B. francana was isolated and characterized as a new zierane-type sesquiterpene called ziera-12(13),10(14)-dien-5-ol (23). In addition, qualitative intraspecies variations of chemical composition were very important particularly for B. francana which possessed three clearly defined different compositions. We report here also the first phytochemical investigation of Acromastigum species. Moreover, crude diethyl ether extract of B. vitatta afforded a new bis(bibenzyl) called vittatin (51), for which a putative biosynthesis was suggested.

International audience; An evaluation of the coloring potential of the different parts of selected plants from New Caledonia has been performed. Among them Hubera nitidissima, an Annonaceae, showed an intense yellow color on fibers. This is the first report of such a coloring potential for a Hubera sp. In this study we present dyeing results obtained with extracts from the leaves of H. nitidissima on linen, silk and wool, color characteristics, dye light-fastness and chemical identity of coloring compounds. The absorbance, K/S index and CIELab coordinates of dyed fibers were measured. Color strength values and fastness properties of the dyed fabrics were high: 7/8 in Blue scale rating. The dyed fibers were analyzed by liquid chromatography hyphenated with UV-Vis spectroscopy and mass spectrometry using UHPLC-DAD-HRMS (ESI-QTOF) instrumentation. We identified two xanthones: mangiferin and homomangiferin together with quercetin glycosides. The hydroalcoholic extract from the leaves was screened for its free radical scavenging properties (DPPH) and showed significant antioxidant activity (26.5 μg/mL). The presence of mangiferin in the Annonaceae family is attested here for the first time. As a result of our study, H. nitidissima appears as an excellent source of light-fast yellow dye with interesting antioxidant properties.

The leaf essential oils of three Eugenia species, E. gacognei Montrouz., E. horizontalis Pancher ex Brongn. & Gris and E. noumeensis Guillaumin, have been examined. Eugenia gacognei was a variable species that contained significant amounts of aromatic ethers, with either 2-hydroxy-4,6-dimethoxy-3,5-dimethyl-acetophenone [1] (36.8% in one collection) or a mixture of 6-hydroxy-2,4-dimethoxy-3-methyl-acetophenone [2] (59.6%) and 2-hydroxy-4,6-dimethoxy-acetophenone [3] (12.7%) in a second collection being the principal components. The remainders of the oil were mixtures of mono- and sesquiterpenes. Eugenia horizontalis gave a terpenoid oil in which the principal components were globulol (18.9%) and spathulenol (14.5%). Eugenia noumeensis also gave a terpenoid oil, with monoterpenes predominating and the major components being 1,8-cineole (47.6%), α-terpineol (10.9%) and α-pinene (7.7%).

Dengue virus is the worldʼs most prevalent human pathogenic arbovirus. There is currently no treatment or vaccine, and solutions are urgently needed. We previously demonstrated that biflavonoids from Dacrydium balansae, an endemic gymnosperm from New Caledonia, are potent inhibitors of the Dengue virus NS5 RNA-dependent RNA polymerase. Herein we describe the structure-activity relationship study of 23 compounds: biflavonoids from D. balansae (1–4) and from D. araucarioides (5–10), hexamethyl-amentoflavone (11), cupressuflavone (12), and apigenin derivatives (13–23). We conclude that 1) over the four different biflavonoid skeletons tested, amentoflavone (1) and robustaflavone (5) are the most promising ones for antidengue drug development, 2) the number and position of methyl groups on the biflavonoid moiety modulate their inhibition of Dengue virus NS5 RNA-dependent RNA polymerase, and 3) the degree of oxygenation of flavonoid monomers influences their antidengue potential. Sotetsuflavone (8), with an IC50 = 0.16 µM, is the most active compound of this series and is the strongest inhibitor of the Dengue virus NS5 RNA-dependent RNA polymerase described in the literature.

Essential oil from leaves of Nemuaron vieillardii (Baill.) Baill., a shrub used in the kanak pharmacopeia, was analyzed by gas chromatography and combined gas chromatography-mass spectrometry. The main compounds identified were safrole (49.7%), linalool (8.0%), δ-cadinene (5.1%), caryophyllene oxide (4%) and α-copaene (2.4%). This chemical composition is consistent with leaf oils of the Atherospermataceae family and demonstrates the proximity of the two genera Nemuaron and Atherosperma as regards to their essential oil compositions. The modified Larval Packet Test (LPT) was used to assess acaricidal effect of N. vieillardii essential oil on larvae of the cattle tick Rhipicephalus (Boophilus) microplus and LC50 was then calculated to 14.67%. High content of safrole in this oil which is suspected of being a human carcinogen, poses the problem of the use of this oil in a perspective of development of alternative tick control strategy and in the traditional medicinal consumption of Nemuaron vieillardii.

The leaf essential oils of the seven endemic New Caledonian species of the genus Melaleuca have been examined. Melaleuca sphaerodendra var. microphylla and Melaleuca brevisepala produced oils in which β-caryophyllene (28.8% and 26.8% respectively) was the principal component. α-Pinene (24.8%) and β-caryophyllene (14.1%) were the principal compounds detected in the leaf oil of Melaleuca pancheri. Melaleuca brongniartii produced an oil in which the principal monoterpenes were α-pinene (23.3%), β-pinene (10.3%) and limonene (19.8%). γ-Terpinene (15.2%), p-cymene (12.8%) and terpinolene (17.5%) were the major components in the leaf essential oil of Melaleuca buseana, whereas the leaf oil of Melaleuca dawsonii contained α-pinene (12.8%) and α-phellandrene (10.3%) as principal components. In Melaleuca gnidioides α-pinene (23.6%), β-pinene (13.6%) and spathulenol (14.7%) were the major components. All of these oils differed from the leaf oil of Melaleuca quinquenervia, an indigenous New Caledonian species also f...

We report 23 cases of poisoning, 4 fatal, due to ingestion of coconut crab, Birgus latro, in New Caledonia. Clinical and biological features of this poisoning are characterized, and the toxin complex is described. We suggest a treatment strategy based on digoxin-specific antibody fragments for patients in a life-threatening condition.

The present study was designed to investigate conazoles as new antileishmanial agents. Several 3-imidazolylalkyl-indoles were prepared under mild reaction conditions and pharmacomodulation at N1 and C5 of the indole ring and at the level of the alkyl chain (R) was carried out starting from the corresponding 3-formylindoles 7-10. All target imidazolyl compounds 38-52 were evaluated in vitro against Leishmania mexicana promastigotes; ketoconazole, amphotericin B and meglumine antimoniate were used as references. Eight out of fifteen compounds (40,43,44,47,48, 50, 51 and 52) exerted similar activity to ketoconazole, with IC50 values in the range of 2.10-3.30 microg/mL. However the most potent compound, 1-(2-bromobenzyl)-3-(1H-imidazol-1-ylmethyl)-1H-indole (38), exhibited IC50 value (0.011+/-0.003 microg/mL) 270-fold lower than that of ketoconazole. Four compounds (38, 43, 50 and 52) were also tested against intracellular amastigotes of L. mexicana; compound 38 exhibited the highest activity with an IC50 value of 0.018+/-0.004 microg/mL.

International audience; The aim of the present study was to demonstrate acaricidal activity on the cattle tick Rhipicephalus (Boophilus) microplus of essential oils from endemic conifers of New Caledonia in the context of the development of natural alternatives. Acaricidal activity of essential oils extracted from resin and heartwood of five endemic conifers of New Caledonia (Araucaria columnaris, Agathis moorei, Agathis ovata, Callitris sulcata, and Neocallitropsis pancheri) was evaluated on 14- to 21-day-old Rhipicephalus microplus tick larvae using the Larval Packal Test bioassay. A first screening with 5 % dilute solution was carried out and the oils with 100 % of mortality at this rate were diluted until no activity was shown. The heartwood oils of the two Cupressaceae were the most active with LC50 value of 0.65 % for C. sulcata and 0.55 % for N. pancheri while resin oil of A. columnaris (LC50=1.62 %) was the most active of the Araucariaceae family. Negative control (ethanol) was not toxic to the larvae. The chemical composition of essential oil from resin of A. columnaris was analyzed by gas chromatography-mass spectrometry. The essential oil was characterized by high level of sesquiterpene hydrocarbons and oxygenated sesquiterpenes and was composed mainly of aromadendrene (23.1 %) and bicyclogermacrene (16.0 %). In order to compare different plant resources in a sustainable program of natural acaricide, an "essential oil efficiency EOE" can be measured as the ratio between the yield of extraction and LC50 value. This study shows that A. columnaris (EOE=2.36) and N. pancheri (EOE=3.51) could provide valuable and effective natural acaricides for control of the cattle tick R. microplus.

In order to find new molecules for antiviral drug design, we screened 102 ethyl acetate extracts from New-Caledonian flora for antiviral activity against the dengue 2 virus RNA-dependant RNA polymerase (DV-NS5 RdRp). The leaf extract of DACRYDIUM BALANSAE, which strongly inhibited the DV-NS5, was submitted to bioguided fractionation. Four biflavonoids ( 1- 4), three sterols ( 5- 7), and two stilbene derivatives ( 8- 9) were identified and evaluated for their antiviral potential on the DV-NS5 RdRp. Biflavonoids appeared to be potent inhibitors of DV-NS5 RdRp with IC 50 s between 0.26 and 3.12 µM. Inhibitory activity evaluations against the RNA polymerase from other Flaviviridae viruses allowed us to conclude that these compounds are specific inhibitors of the DV RNA polymerase. The strongest inhibitions were observed with hinokiflavone ( 4), but podocarpusflavone A ( 2) is the strongest noncytotoxic inhibitor of the DV-NS5 and it also displayed polymerase inhibitory activity in a DV replicon. A preliminary structure-activity relationship study (SARs) revealed the necessity of the biflavonoid skeleton, the influence of number and position of methoxylations, and the importance of a free rotation of the linkage between the two apigenin monomers of the biflavonoids. To the best of our knowledge, podocarpusflavone A ( 2) is the strongest noncytotoxic non-nucleotide molecule exhibiting a specific inhibitory activity against the RNA polymerase domain of DV-NS5 and thus is promising for chemotherapy development against dengue fever.

As part of our search for new antimalarial drugs in South Pacific marine sponges, we have looked for inhibitors of Pfnek-1, a specific protein kinase of Plasmodium falciparum. On the basis of promising activity in a preliminary screening, the ethanolic crude extract of a new species of Pseudoceratina collected in Vanuatu was selected for further investigation. A bioassay-guided fractionation led to the isolation of a derivative of homogentisic acid [methyl (2,4-dibromo-3,6-dihydroxyphenyl)acetate, 4a] which inhibited Pfnek-1 with an IC(50) around 1.8 muM. This product was moderately active in vitro against a FcB1 P. falciparum strain (IC(50) = 12 muM). From the same sponge, we isolated three known compounds [11,19-dideoxyfistularin-3 (1), 11-deoxyfistularin-3 (2) and dibromo-verongiaquinol (3)] which were inactive against Pfnek-1. Synthesis and biological evaluation of some derivatives of 4a are reported.

As part of our search for new antimalarial drugs, we have screened for inhibitors of Pfnek-1, a protein kinase of Plasmodium falciparum, in south Pacific marine sponges. On the basis of a preliminary screening, the ethanolic crude extract of a new species of Xestospongia collected in Vanuatu was selected for its promising activity. A bioassay-guided fractionation led us to isolate xestoquinone which inhibits Pfnek-1 with an IC50 around 1 mu M. Among a small panel of plasmodial protein kinases, xestoquinone showed modest protein kinase inhibitory activity toward PfPK5 and no activity toward PfPK7 and PfGSK-3. Xestoquinone showed in vitro antiplasmodial activity against a FCB1 P. falciparum strain with an IC50 of 3 mu M and a weak selectivity index (SI 7). Xestoquinone exhibited a weak in vivo activity at 5 mg/kg in Plasmodium berghei NK65 infected mice and was toxic at higher doses. (c) 2006 Elsevier Ltd. All rights reserved.

Introduction Neriifolin is a cardenolide structurally closed to digoxin and is contained in the fruit kernel of the red-eye-sea mango tree ( Cerbera manghas ), on which the coconut crab feeds. We previously reported lethal neriifolin poisonings following the consumption of New Caledonian coconut crabs Birgus latro (Maillaud et al., Toxicon 2010). This led us to consider digoxin-specific Fab antibody fragments (Fab) as a specific treatment. This presentation focuses on two cases of successful Fab use. Methods Case #1 (Maillaud et al., Toxicon 2012): a 63-year-old female was admitted to the ER. She had eaten a coconut crab 19 hours previously. ECG showed first-degree atrio-ventricular block (AVB), specific repolarisation abnormalities and prolonged cardiac pauses. Fab (760 mg) were then administered intravenously 21 hours after the toxic meal. No more cardiac pause was reported and the patient was discharged one week later. Case #2: a 73-year-old man complained of vomiting after having eaten a coconut crab a few hours before. He was admitted to the ER. ECG monitoring showed bradycardia (32 to 45 beats/min), arrhythmia and cardiac pauses. Fab were administered (380 mg IV = 10 units). 10 other units were administered 3 hours later in the ICU. Cardiac pauses disappeared and cardiac frequency went close to normal. The patient was discharged at day 2. Different blood samples were analysed. Neriifolin was determined by LC-IT-MS/MS. Table Abstract O43. Case #1 (admission) Case #1 (ICU before Fab) Case #1 (12h after Fab) Case #2 (2h after 1 st Fab) Case #2 (5h after 2 nd Fab) Case #2 (8h after 2 nd Fab) Neriifolin Serum: 1.30 Serum: 0.59 Serum: 3.04 Serum: Plasma: Whole blood: 3.17 Serum: 5.01 Serum: 3.90 Plasma: 4.36 Results Neriifolin blood concentrations (ng/mL): In both cases, neriifolin concentrations increased after the Fab perfusions. As digoxin, neriifolin leaves cardiac receptors to be bound to Fab fragments, and is then eliminated. Surprisingly, as shown in case #2, neriifolin whole blood concentration is much higher than in serum and in plasma. Like digoxin, haemoglobin could be the neriifolin binding site in blood. This may implicates that in cardenolides poisoning, low serum and plasma concentrations should be considered with caution. Two other C. manghas cardenolides of interest: cerberigenin and cerberin, were not detected in all nine samples. Conclusion Digoxin-specific Fab antibody fragments have been effective in the treatment of two life-threatening coconut crab poisonings. Such therapy should be considered in patients showing heart conduction disturbances. As with digoxin, in each case we note a rise in total (free + bound) neriifolin blood concentrations after antidote administration. In Case #2 whole blood concentration was more than 30 times higher than serum and plasma concentrations. To avoid false negative results we suggest considering also whole blood analysis in case of suspected cardenolide intoxications. Reversibility of the RBC partitioning has been shown for digoxin and haemoglobin could be a storage compartment for neriifolin which would explain the need for the supplemental Fab dose in Case #2.

The volatile components obtained by hydrodistillation of leaves of C. neocaledonica Dummer, C. sulcata (Parlatore) Schlechter and N. pancheri (Carrière) de Laubenfels from New Caledonia were investigated for the first time by a combination of GC and GC–MS analysis, and compared with the heartwood oil compositions of the three species. The essential oils from C. sulcata and C. neocaledonica leaves contain a majority of monoterpenes while the leaf oil of N. pancheri is characterized by a high level of sesquiterpenoids. On the basis of the sesquiterpenoid composition of the wood- and leaf oils, N. pancheri is closely related to both New Caledonian Callitris spp. However, C. sulcata and C. neocaledonica oils remain distinct from N. pancheri and the Australian Callitris oils by the presence of compounds biosynthetically related to the bisabolyl cation, mainly barbatenes and thujopsene.

A series of fluconazole analogues 5 – 20 incorporating azaindole and indole moieties were prepared using oxirane intermediates synthesized under microwave irradiation. All of the compounds were evaluated in vitro against two clinically important fungi, Candida albicans and Aspergillus fumigatus . Four derivatives 6 , 13 , 14 and 18 exerted high antifungal activity against C. albicans with MIC 80 values 3- to 28-fold lower than that of fluconazole.

A biochemical and phytochemical study of Diospyros macrocarpa Hiern, an endemic plant of New Caledonia, was realized. Indeed, bark and leaf extracts were tested for their cytotoxic and antibiotic activities as well as for their radical scavenging properties. Methanol extracts showed promising radical scavenging activity with an IC50 value of 5.6 ± 0.9 μg/mL for the leaves and 8.1 ± 1.4 μg/mL for the barks. The ethyl acetate extract from the barks showed strong and selective activity against NCI-H727 cancer cell line with an IC50 value of 9.5 ± 0.6 μg/mL.. Two new cyclobutane dimers: macrocarpasin A (1) and B (2) (figure 1) together with six known compounds: yangonin (3), betulinic acid (4), α-amyrin (5), β–amyrin (6), loliolide (7) and oleanderolide (8) were isolated from leaf extracts. Their structures were established by 1D and 2D NMR along with HRMS analyses. Cytotoxic activities of isolated compounds were also evaluated. None of them showed interesting cytotoxicity against the seven tested cancer cell lines.