Marine Natural Meroterpenes: Synthesis and Antiproliferative Activity

Meroterpenes are compounds of mixed biogenesis, isolated from plants, microorganisms and marine invertebrates. We have previously isolated and determined the structure for a series of meroterpenes extracted from the ascidian Aplidium aff. densum. Here, we demonstrate the chemical synthesis of three of them and their derivatives, and evaluate their biological activity on two bacterial strains, on sea urchin eggs, and on cancerous and healthy human cells

CO-FREE Alternative Test Products for Copper Reduction in Agriculture

The project CO-FREE (2012-2016) aimed to develop strategies to replace/reduce copper use in organic, integrated and conventional farming. CO-FREE alternative test products (CTPs) were tested and integrated together with decision support systems, disease-tolerant varieties, and innovative breeding goals (ideotypes) into improved management strategies. CO-FREE focused on apple/apple scab (Venturia inaequalis), grape/downy mildew (Plasmopara viticola), and tomato and potato/late blight (Phytophthora infestans). Starting point of the project were ten CTPs with direct or indirect modes of action including Trichoderma atroviride SC1 and protein extract SCNB, Lysobacter spp., yeast-based derivatives, Cladosporium cladosporioides H39, the oligosaccharidic complex COS-OGA, Aneurinibacillus migulanus and Xenorhabdus bovienii, sage (Salvia officinalis) extract, liquorice (Glycyrrhiza glabra) extract, PLEX- and seaweed plant extracts. As the project progressed, further promising CTPs were included by the partners. Field trials were performed in different European countries in 2012-2015 following EPPO standards. In the first years, stand-alone applications of CTPs were tested. In the following years these were integrated into complete strategies. Effects on main and further diseases, on yield and on non-target organisms were assessed. Here, field trial results with CTPs are summarized

Impact of Marine Drugs on Animal Reproductive Processes

The discovery and description of bioactive substances from natural sources has been a research topic for the last 50 years. In this respect, marine animals have been used to extract many new compounds exerting different actions. Reproduction is a complex process whose main steps are the production and maturation of gametes, their activation, the fertilisation and the beginning of development. In the literature it has been shown that many substances extracted from marine organisms may have profound influence on the reproductive behaviour, function and reproductive strategies and survival of species. However, despite the central importance of reproduction and thus the maintenance of species, there are still few studies on how reproductive mechanisms are impacted by marine bioactive drugs. At present, studies in either marine and terrestrial animals have been particularly important in identifying what specific fine reproductive mechanisms are affected by marine-derived substances. In this review we describe the main steps of the biology of reproduction and the impact of substances from marine environment and organisms on the reproductive processes

Synthesis of the Bioactive Benzochromenes Pulchrol and Pulchral, Metabolites of Bourreria pulchra

The parasites Leshmania mexicana and Trypanosoma cruzi cause serious health problems, and few efficient treatments are available. Recently, the two benzochromenes pulchrol (1) and pulchral (2) were reported from the roots of Bourreria pulchra, and especially 1 but also 2 was found to be active towards the parasites. In this paper, we present a total synthesis of 1 and 2 to facilitate their biological evaluation. The synthesis is mild, short, and high yielding and suitable for a structure-activity relationship study

Antibacterial activity of carob (Ceratonia siliqua L.) extracts against phytopathogenic bacteria Pectobacterium atrosepticum

International audienc

Quinone and Hydroquinone Metabolites from the Ascidians of the Genus Aplidium

Ascidians of the genus Aplidium are recognized as an important source of chemical diversity and bioactive natural products. Among the compounds produced by this genus are non-nitrogenous metabolites, mainly prenylated quinones and hydroquinones. This review discusses the isolation, structural elucidation, and biological activities of quinones, hydroquinones, rossinones, longithorones, longithorols, floresolides, scabellones, conicaquinones, aplidinones, thiaplidiaquinones, and conithiaquinones. A compilation of the 13C-NMR spectral data of these compounds is also presented

Reagent-Controlled Cyclization-Deprotection Reaction to Yield either Fluorenes or Benzochromenes

Compounds with benzochromene and fluorene structures are common in nature and society, and they can have potentially useful biological activities. In this paper, conditions for the selective preparation of either a benzochromene or a fluorene from the same starting material are described. The procedure uses a reagent-controlled cyclization-demethylation to give the benzochromene, or an intramolecular Friedel-Crafts-type alkylation to give the fluorene

Deleterious mutations in the essential mRNA metabolism factor, hGle1, in amyotrophic lateral sclerosis

International audienceAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective death of motor neurons. Causative mutations in the global RNA-processing proteins TDP-43 and FUS among others, as well as their aggregation in ALS patients, have identified defects in RNA metabolism as an important feature in this disease. Lethal congenital contracture syndrome 1 and lethal arthrogryposis with anterior horn cell disease are autosomal recessive fetal motor neuron diseases that are caused by mutations in another global RNA-processing protein, hGle1. In this study, we carried out the first screening of GLE1 in ALS patients (173 familial and 760 sporadic) and identified 2 deleterious mutations (1 splice site and 1 nonsense mutation) and 1 missense mutation. Functional analysis of the deleterious mutants revealed them to be unable to rescue motor neuron pathology in zebrafish morphants lacking Gle1. Furthermore, in HeLa cells, both mutations caused a depletion of hGle1 at the nuclear pore where it carries out an essential role in nuclear export of mRNA. These results suggest a haploinsufficiency mechanism and point to a causative role for GLE1 mutations in ALS patients. This further supports the involvement of global defects in RNA metabolism in ALS

EU-project CO-FREE: innovative strategies for copper-free low input and organic farming systems

The EU-project CO-FREE was launched in January 2012 (grant agreement number 289497, duration 54 months). The aim of this project is the development of innovative strategies for replacement of copper in European organic and low input fruit, grapevine, potato, and tomato production systems. The focus is set on the most copper-relevant diseases, including Venturia inaequalis, Plasmopara viticola and Phytophthora infestans. A collaboration of 21 partners, including 11 academic and 10 industry (all small and medium enterprises) partners from 11 European countries, is working towards achievement of this goal. Thereby, the project follows a construction kit system consisting of different tools, including e.g. decision support systems, disease tolerant varieties, cropping systems (including agro-forestry) and alternative compounds/bicontrol agents. Starting points of the project were results of former projects (e.g. REPCO, BlightMop, ENDURE). Twelve of the most promising and advanced pipeline compounds of plant and microbial origin, derived from these EU and national research projects, and from R&D funded by SMEs have been selected for further investigation in CO-FREE. The chosen agents fulfill the following criteria: (i) proven efficacy against at least one of the major copper-controlled diseases, with specific, clearly identified aspects remaining to be improved in the frame of the project (e.g rainfast formulation, clarification of mode of action for optimization of the application parameters), (ii) novelty, and (iii) involvement of a leading/innovative SME company ensuring further development and marketing. The CO-FREE partners are further developing these control agents, and identify their impact on diseases in small scale greenhouse and field trials. Following the construction kit system, control agents are combined with other above mentioned tools, so that finally practice-relevant control strategies will be generated