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A numerical model was used to predict toxic microalgal transport and dispersion in Ria de Aveiro in Portugal. A previously developed Lagrangean particle tracking model coupled to a calibrated two-dimensional hydrodynamic model of Ria de Aveiro was used. Microalgae were regarded as passive particles and the methodology used allowed the determination of their trajectories, as induced by the tidal currents predicted by the hydrodynamic model. The model assumes Ria de Aveiro as vertically homogeneous and does not take into account the vertical distribution patterns of microalgae. Simulations were carried out during extreme spring and neap tides, with microalgal released at the mouth of the lagoon at the local flood. The maximum and minimum areas affected during the occurrence of toxic microalgal blooms were estimated to evaluate the suitability of the distribution of the sampling stations included in the local monitoring program. It was found that the tidal currents greatly determine the microalgal horizontal distribution and dispersal in the lagoon. The results confirmed that the locations of water and bivalve shellfish sampling stations, postulated by INIAP/IPIMAR, in the context of the local harmful algal bloom (HAB) program, were appropriate, although some possible refinements were identified.

Activation of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) underlies the course of several human pathological conditions and, to date, no efficacious therapeutic IDO inhibitors are available. We proposed to develop a robust screening system based on the use of yeast cells to identify new lead compounds for the pharmacological inhibition of IDO-the BLOCKADE platform. Yeast combines the advantages of a relevant surrogate model for eukaryotic cell processes with the amenity to miniaturization and automation. We brought added value to the system by increasing the stringency of our assay, as the BLOCKADE strain was not deleted for any efflux pump, thus creating additional challenges for test compounds to be identified as hits. Screening of a library of 50 080 small molecules led to the identification of 101 potential IDO inhibitors, a low hit rate of 0.2%, reflecting the stringent assay conditions imposed. Most important, secondary pharmacology assays in mammalian cells confirmed activity for 76% of the hits, whereas hepatotoxicity testing indicated that 87% of them displayed a safe profile. The high predictivity rates obtained using the BLOCKADE platform clearly validate our system as a powerful tool for drug discovery.

Among marine organisms, sponges are the richest sources of pharmacologically-active compounds. Stemming from a previous lead discovery program that gathered a comprehensive library of organic extracts of marine sponges from the off-shore region of Portugal, crude extracts of Erylus cf. deficiens collected in the Gorringe Bank (Atlantic Ocean) were tested in the innovative high throughput screening (HTS) assay for inhibitors of indoleamine 2,3-dioxygenase (IDO) and showed activity. Bioassay guided fractionation of the dichloromethane extract led to the isolation of four new glycolipids, named erylusamide A–D. The structures of the isolated compounds were established by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and chemical derivatization. The metabolites shared a pentasaccharide moiety constituted by unusual highly acetylated d-glucose moieties as well as d-xylose and d-galactose. The aglycones were unprecedented long chain dihydroxyketo amides. Erylusamides A, B and D differ in the length of the hydrocarbon chain, while erylusamide C is a structural isomer of erylusamide B.