Naegleria fowleri is the etiological agent of primary amoebic meningoencephalitis, a fulminant infection of the central nervous system that leads to death in most cases. Currently, no standardised therapy is available, and existing treatments are limited by inconsistent efficacy and significant toxicity. β-Hydroxy-γ-lactones previously described as trypanocidal and leishmanicidal agents share structural features, a reactive lactone carbonyl and a stereodefined hydroxyl group, that are commonly linked to disruption of redox and mitochondrial homeostasis in protozoan parasites. Based on this precedent, we hypothesised that the same scaffold could also be active against N. fowleri. Fourteen compounds, ten previously reported β-hydroxy-γ-lactones and four newly synthesised α, β-unsaturated-γ-lactones (butenolides, SAM-13 to SAM-16) obtained by β-elimination, were evaluated in vitro against the trophozoite and cyst stages of two N. fowleri strains (ATCC® 30808™ and ATCC® 30215™), together with cytotoxicity assays in murine macrophages (J774A.1) and human SH-SY5Y neuroblastoma cells. SAM-1 and SAM-5 emerged as the most active molecules, with low-micromolar IC₅₀ values against both trophozoites and cysts; their selectivity, however, differed markedly, with SAM-5 showing a substantially wider safety margin (selectivity index up to 12.9) than SAM-1 (selectivity index of 1.2 in neuroblastoma cells), underscoring selectivity as a key parameter for further optimisation. In contrast, three of the four newly synthesised butenolides were essentially inactive (IC₅₀ > 160 μM); the fourth, SAM-14 (derived from SAM-5), retained measurable but poorly selective activity (IC₅₀ = 56.9 μM, SI = 1.35), indicating that the requirement for the free β-hydroxyl group is substituent-dependent and providing an initial structure–activity relationship for this scaffold. Mechanistic assays showed that SAM-1 and SAM-5 induced hallmarks of programmed cell death in N. fowleri trophozoites, including phosphatidylserine externalisation, chromatin condensation, mitochondrial depolarisation, ROS overproduction, and F-actin disorganisation, together with complementary evidence of autophagic vacuole formation. In silico ADME profiling predicted favourable drug-likeness for SAM-1 and SAM-5, including compliance with Lipinski's rule of five, high gastrointestinal absorption and predicted blood–brain barrier permeability, with neither compound predicted to be a P-glycoprotein substrate. Taken together, these findings identify β-hydroxy-γ-lactones as promising, CNS-penetrant scaffolds for anti-Naegleria drug discovery and outline the structural determinants that should guide their future optimisation.

Improving crop performance under water scarcity requires fertilization strategies that not only supply nutrients but also strengthen soil–plant interactions. In this work, we evaluated a compost tea obtained from recycled organic by-products using the “Sistema de Elaboración de Fertilizante Ecológico Líquido” (SEFEL) system, as a multifunctional biofertilizer in tomato (Solanum lycopersicum) and lettuce (Lactuca sativa) grown under well-watered (WW) and deficit irrigation conditions (WD). We explored its capacity to modulate physiological responses, metabolic adjustments and soil microbiota under WW and WD. SEFEL compost tea application consistently promoted plant growth. Tomato plants showed a 63.9% increase in leaf dry weight under optimal irrigation and a 32.6% increase under WD, while root biomass rose by 30.3% and 53.3%, respectively. In lettuce, leaf dry weight increased by 34% under WW and by 23% under WD. Although drought reduced photosynthetic rates in both species, SEFEL compost tea-treated plants maintained higher carbon assimilation and stomatal conductance during prolonged stress, indicating improved physiological adjustment. These responses were accompanied by a greater accumulation of proline and soluble carbohydrates under water deficit. Interestingly, a different activation of the raffinose family oligosaccharides (RFOs) pathway was detected in tomato and lettuce, pointing to species-specific metabolic strategies. Additionally, SEFEL compost tea improved nutrient uptake under both irrigation regimes and promoted shifts in soil microbial communities, suggesting reinforced soil–plant connectivity. Our results indicate that SEFEL compost tea acts as an integrative soil–plant biostimulant, enhancing nutrient acquisition and drought tolerance while contributing to organic waste valorisation within sustainable production systems.

Diseases caused by Leishmania spp. and Trypanosoma spp. parasites provoke thousands of annual deaths. The current treatments exhibit noticeable disadvantages such as low effectiveness, high cost, side-effects, and the occurrence of resistance. Thus, the search for new drugs is mandatory, and diversity-oriented synthesis appears as a useful tool to access libraries of small, structurally diverse, and potentially bioactive compounds in few steps. In this work, a battery of 10 new and highly substituted β-hydroxy-γ-lactones was straightforwardly synthesized from β,γ-unsaturated N-acyl oxazolidin-2-ones and evaluated against Leishmania amazonensis and Trypanosoma cruzi. Six of the compounds were found to exhibit antiparasitic activity against T. cruzi epimastigotes and/or L. amazonensis promastigotes, as well as against the amastigote forms of both parasites; among these, two compounds stood out against L. amazonensis, with selectivity indices (SI) higher than that of the reference drug. Furthermore, these two compounds appear to induce apoptosis-like cell death in L. amazonensis, as suggested by mechanistic studies. It is worth noting that the compound SAM-2 exhibited an SI four times higher than miltefosine, due to its lower toxicity compared to this drug, highlighting its potential as a promising candidate for the development of new therapies.

In this work, we report the synthesis and structural characterization of a novel organometallic bipyridine-based atropisomer featuring two (S)-BINOL-derived units, each functionalized with a ferrocene moiety and linked by a 4,4′-disubstituted 2,2′-bipyridine bridge. Although the molecule appears symmetric, single-crystal X-ray diffraction establishes its axial chirality, as demonstrated by Flack x = −0.020(14) and Hooft x = 0.013(18) parameters. The bipyridine core, sterically hindered by the bulky ferrocenyl groups, imposes a rigid atropisomeric structure. To better understand this behavior, a new Cu(II) complex is presented to examine how peripheral substitution affects the accessibility and coordination capacity of the bipyridine core; these factors ultimately dictate the solid-state atropisomerism and rigidity of the resulting multinuclear architecture.

Acanthamoeba spp. are ubiquitous protozoa and the causative agents of severe human infections, including granulomatous amoebic encephalitis (GAE) and Acanthamoeba keratitis (AK). The lack of standardised and fully effective treatments highlights the urgent need for novel therapeutic agents. In this study, we evaluated the in vitro amoebicidal activity of 8 cyanoacrylamide derivatives (QOET) against three different strains of Acanthamoeba: A. castellanii Neff, A. griffini and A. polyphaga. Among the tested compounds, QOET-112 and 114 displayed the lowest IC50 values against both the trophozoite and cyst stages compared to the other derivatives. Furthermore, these compounds demonstrated low cytotoxicity against the murine macrophage cell line J774A.1. Analysis of the mode of action evidenced that both cyanoacrylamides triggered programmed cell death (PCD) and autophagy in A. griffini trophozoites. Additionally, these compounds induced severe cytoskeletal alterations, specifically characterised by the disorganisation and disruption of the actin and tubulin networks.

Laurinterol, a halogenated sesquiterpene produced by red algae of the genus Laurencia, is one of the most characteristic compounds within the laurane and cyclolaurane families. This review compiles and examines current knowledge on laurinterol, integrating evidence on its occurrence, biosynthesis, biological activities, and structural features. Within a functional and ecological framework, laurinterol is proposed as an archetypal Smart Secondary Metabolite (SSM), a concept that reflects the convergence of structural singularity, high abundance within its biosynthetic context, broad biological activity, multi-target interactions, and ecological or chemotaxonomic relevance. This perspective highlights its role in adaptive processes within producing organisms and associated trophic networks. Laurinterol exhibits a broad bioactivity profile, including antimicrobial, antimycobacterial, cytotoxic, antiparasitic, enzyme inhibitory, antifouling, and insecticidal or repellent effects. Structure–activity relationship (SAR) studies remain limited and are mainly developed in specific models, particularly against Naegleria fowleri. The current intellectual property landscape related to laurinterol, including patent applications, granted patents, and technological development trends, is also examined. Overall, this review positions laurinterol as a structurally distinctive and functionally relevant marine metabolite within chemical ecology and marine natural products research.

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.

Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a serious public health concern, particularly in Latin America, due to its high prevalence and the limited efficacy and safety of current treatments. To identify new potential therapeutic options, a library of 40 synthetic indole derivatives was screened for antiparasitic activity. The compounds were tested against both epimastigote and intracellular amastigote forms of T. cruzi using in vitro assays. While most of the molecules showed low or no activity, ten compounds exhibited promising effects with IC₅₀ values below 200 μM. The most active derivatives were further evaluated for cytotoxicity on mammalian cells. Among them, the compound I – 7b stood out with a selectivity index of 19.8 and was selected for further characterization. Subsequent assays revealed that this compound induced several cellular effects in the parasite, including ATP depletion, chromatin condensation, plasma membrane damage, reactive oxygen species (ROS) accumulation, and disruption of mitochondrial membrane potential (ΔΨm). These findings suggest that certain indole-based compounds may serve as promising scaffolds for the development of novel therapies against T. cruzi, contributing to the advancement of global health efforts targeting neglected tropical diseases.

The concept of “Smart Secondary Metabolites” is introduced here to describe a privileged class of natural products defined by structural originality, biosynthetic adaptability, and broad interaction potential with biological systems. Elatol, a halogenated sesquiterpene chiefly produced by Laurencia red seaweeds and occasionally accumulated by their consumers, exemplifies this concept with remarkable clarity. Its biosynthesis unfolds from farnesyl diphosphate via γ-bisabolane cations, bromochlorination, and stereoselective cyclization to chamigrene scaffolds, generating both (+)- and (–)-enantiomers, two metabolites with clearly distinct potential ecological roles and pharmacological profiles. This review synthesizes the current state of knowledge on elatol’s distribution, biosynthetic origins, ecological relevance, and therapeutic potential. Elatol serves as a multifunctional chemical mediator, fulfilling defensive, communicative, and regulatory roles whose intensity shifts in response to herbivory, biofouling, temperature, and salinity. In parallel, its potent activities against infectious, metabolic, and neoplastic diseases highlight its growing value as a drug lead, reflected in a rising number of patent claims. Altogether, elatol emerges as a model Smart Secondary Metabolite whose ecological sophistication and biochemical versatility position it as a promising scaffold for marine-derived drug discovery.

A practical and efficient regio- and stereoselective hydrophosphorylation of propiolates, as well as a multicomponent reaction incorporating an aldehyde component, is reported. Both processes proceed with atom economy in very straightforward experimental procedures. The reactions are catalyzed by DABCO (1,4-diazabicyclo[2.2.2]octane) and use readily available H-phosphonates as the phosphorylating agent.