Vector control against infectious diseases: Towards the sustainable development of insect repellents in New Caledonia

More than 80% of the world’s population is threatened by vector-borne diseases with populations in tropical regions most at risk. The World Health Organization (WHO) thus promotes the use of mosquito repellents to prevent infectious diseases. In New Caledonia, the office of Social and Health Affairs Direction (DASS) approved 4 active substances of insect repellents for personal anti-vector protection, among these para-menthan-3,8-diol or PMD. This joint-project between James Cook University (JCU) and the University of New Caledonia (UNC) aimed to identify essential oil bearing plants within the flora of New Caledonia that can supply significant quantities of PMD or its precursor citronellal. The study subsequently identified the essential oil of Corymbia citriodora (Hook.) K.D.Hill & L.A.S.Johnson of the Myrtaceae family already produced in New Caledonia as an important candidate for the production of PMD. This oil provides a significant amount of citronellal, which after an acid-catalyzed thermal cyclisation hydration sequence leads to a mixture of cis and trans isomers of PMD. On the basis of a published method, a standard operating procedure for the conversion of citronellal to PMD has been provided to a distillery in New Caledonia. The distillery has since produced and marketed this renewable insect repellent

Antiplasmodial Activities of Homogentisic Acid Derivative Protein Kinase Inhibitors Isolated from a Vanuatu Marine Sponge Pseudoceratina sp.

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 IC50 around 1.8 μM. This product was moderately active in vitro against a FcB1 P. falciparum strain (IC50 = 12 μM). 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

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores.

Funder: Funder: Fundación bancaria ‘La Caixa’ Number: LCF/PR/PR16/51110003 Funder: Grifols SA Number: LCF/PR/PR16/51110003 Funder: European Union/EFPIA Innovative Medicines Initiative Joint Number: 115975 Funder: JPco-fuND FP-829-029 Number: 733051061Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer's disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer's disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer's disease

Synthèse et évaluation pharmacologique de composés indoliques ou apparentés à activité antifongique et antileishmanienne

Une série de dérivés indoliques, portant une chaîne 2-phényl-l-(1H-1,2,4-triazol-1-yl)propan-2-ol en position N-1 du noyau indolique, ont été synthétisés sous activation micro-ondes puis évalués pour leurs activités antifongique et antileishmanienne, par inhibition de la 14alpha-déméthylase. Au vu des résultats pharmacologiques de cette série, les travaux de pharmacomodulation ont consisté en la substitution de l'indole par des hétérocycles azotés et du H1-1,2,4-triazole par divers noyaux azolés. Le haut niveau d'activité antifongique de ces molécules sur Candida albicans, nous a conduits à séparer sur colonne chirale les énantiomères des mélanges racémiques et à synthétiser des pro-drogues afin d'observer l'activité in vivo sur des modèles systémique et topique de souris. La fixation en position C-3 du noyau indolique et l'allongement de la chaîne 2-phényl-l-(1H-1,2,4-triazol-1-yl)propan-2-ol ont été étudiés dans le but d'élargir le spectre d'activité de cette famille de composés. Toutes les activités in vitro sont comparées à l'amphotéricine B, au fluconazole, au kétoconazole, à l'itraconazole et à l'antimoniate de méglumine.A new series of azole derivatives of 2-aryl-3-indolyl-l-triazolyl-2-propanol were designed and prepared from the corresponding oxiranes by a newly developed ring-opening reaction carrying under micro-wave irradiations. All target compounds were evaluated for antifungal and antileishmanial activities. Test fangal strains (Candida albicans, C. krusei, C. parapsilosis, Aspergillus fumigatus, Microsporum cams, Trichophyton mentagrophytes) were obtained for the ATCC or were clinical isolates. Further pharmacomodulation works were accomplished by replacement of indole; heterocycles such as 7-azaindole, benzimidazole and benzotriazole were used. Fixation of propan-2-ol chain at C-3 on indole was also studied with the aim to get a broader antifungal spectrum. The high level activities on Candida albicans encouraged us to separate the enantiomers from racemic mixtures. Enantiomers were directly separated by HPLC using cellulose tris (3,5-dimethylphenylcarbamate) as a chiral stationary phase. The S-enantiomer of 2-(2,4-dichlorophenyl)-3-(1H-indol-l-yl)-l-(1H-l,2,4-triazol-lyl)propan-2-ol showed potent antifungal activity against Candida albicans in vivo. All target compounds are compared to amphotericin B, ketoconazole, fluconazole, itraconazole and meglumine antimoniate.NANTES-BU Médecine pharmacie (441092101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Editorial: Exploring the unique biodiversity of the Western Pacific to identify novel anti-infectious and anti-inflammatory compounds of natural origin

International audienceNo abstract availabl

Antioxidant Compounds from Microalgae: A Review

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

Antioxidant activities and volatile compounds analysis of coproducts from conifers of logging industry in New Caledonia

International audienc

OMICS Approaches to Assess Dinoflagellate Responses to Chemical Stressors

Dinoflagellates are important primary producers known to biosynthesize metabolites of interest and toxins and form Harmful Algae Blooms (HABs). Water conditions such as nutrient availability, anthropogenic contaminants or pH impact dinoflagellate toxin productions, and HABs' formation remains unclear. In this review, we present the recent contributions of OMICs approaches to the investigation of dinoflagellate responses to water chemical stressors. Transcriptomic and proteomic studies highlight whole-cell strategies to cope with nutrient deficiencies. Metabolomic studies offer a great view of toxin, lipid and sugar productions under stressors. However, the confrontation of different OMICs studies is tedious, as approaches are conducted in different species. As for other model organisms, it would be interesting to use multi-OMIC approaches to build a complete view of dinoflagellate responses to chemical stressors. Overcoming the complex genome of dinoflagellates and increasing their genomic resources is therefore essential to push further. The combination of OMICs studies will provide a much-needed global view of molecular processes, which is essential to optimize the production of dinoflagellate metabolites of interest and identify markers of HABs' formation and toxin production events