Instituto de Productos Naturales y Agrobiología

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.

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.