Marine Drugs

In recent years, the pufferfish Lagocephalus lagocephalus has been recorded with unusual frequency in coastal areas of the Canary Islands. The most notable episodes occurred in March and November 2017, when numerous shoals were observed along the coasts of the Western Canary Islands. A toxicological study of these episodes was carried out, analyzing liver, kidney, gonads, skin, and muscle of a representative population. In all toxic samples (33.3% and 41.7% of specimens in March and November 2017, respectively), only the liver extract showed toxicities, using a mouse biological assay (MBA). The toxicological profile was determined by UHPLC-MS-MS, identifying saxitoxin (STX) and tetrodotoxin (TTX) congeners. This analytical methodology was optimized to determine 26 marine toxins. Thus, in the March 2017 episode, the toxicological profile was characterized by the co-occurrence of tetrodotoxins (TTX and 4-epiTTX) and paralytic shellfish toxin (PST) analogues (dcSTX, dcneoSTX, and doSTX); however, STX and neoSTX emerged as the dominant toxins in specimens collected during the November 2017 episode. The results show that L. lagocephalus in the Canary Islands presents a variable and dynamic toxicological profile, strongly influenced by environmental factors. These findings highlight the need for continued monitoring and for analytical approaches capable of capturing this complexity and assessing potential risks to public health.

An isolate of the diatom Staurosirella pinnata is a promising platform for drug discovery due to its ability to produce bioactive metabolites. As previously shown, S. pinnata extracts exhibit bioactivities, with hydrophilic fractions showing selective cytotoxicity against human melanoma cells and lipidic fractions promoting thermogenesis in murine white adipocytes. In this work, we focused on the interaction between S. pinnata metabolism and light irradiance exposure to evaluate bioactivity targeting medulloblastoma cells. Cultures under standard, control, irradiance (80 µmol photons m⁻² s⁻¹) were exposed in the stationary phase to increased light intensities (200 and 600 µmol photons m⁻² s⁻¹) for 126 h. Growth, photosynthetic performance and metabolic profile were monitored, while the bioactivity of small-molecule fractions was assessed at the end. Exposure to 200 µmol photons m⁻² s⁻¹ significantly enhanced growth (92.6% increase in absorbances compared to the control), whereas 600 µmol photons m⁻² s⁻¹ induced growth inhibition (41.3% decrease in absorbances with respect to the control culture) and impaired photosynthesis. Metabolomic analysis revealed a shift from carbohydrate to lipid metabolism. Bioactivity assays showed that extracts from the highest irradiance exhibited cytotoxic effects on medulloblastoma cells, similar to the 80 µmol photons m⁻² s⁻¹ cultures on DAOY (68% vs. 82% of cell death induction levels, respectively), while intermediate irradiance did not show a significant effect in any of the tested cell lines. The results showed that different light intensities impact S. pinnata metabolism, demonstrating effects exploitable for drug discovery and the importance of investigating the impact of cultivation parameters in modulating S. pinnata bioactivity potential.

Thirteen new decaline polyketides, namely, zosteropenillines T–W (1–4), 8-hydroxypallidopenilline A (5), 13-epi-zosteropenilline P (6), 11-epi-zosteropenilline N (7), 15-hydroxyzosteropenilline M (8), 8-hydroxyzosteropenilline M (9), 11-epi-zosteropenilline M (10), and zosteropenillines X–Z (11–13), along with 17 known related compounds (14–30) were isolated from the ethyl acetate extract of the marine-derived fungus Penicillium yezoense KMM 4679 cultivated on MgCl₂-containing nutrient medium. The structures of the isolated compounds were established based on spectroscopic methods. The absolute configurations of zosteropenillines T (1) and V (3) were determined using time-dependent density functional theory (TD-DFT) calculations of the ECD spectra. X-ray diffraction analysis data were obtained for the known zosteropenilline S (28). A biogenetic pathway for 1–13 was proposed. The effects of the compounds on Staphylococcus aureus and Candida albicans growth and biofilm formation were observed. Zosteropenillines U (2), Y (12) and Z (13) with higher activity against C. albicans biofilms were nontoxic for normal cardiomyocyte H9c2 cells, making them promising anti-candidal agents. Moreover, zosteropenillines U and Y demonstrated cardioprotective effects in acute ischemia/reperfusion and CoCl₂-mimicking hypoxia in vitro models.