To explore new compounds with antitumour activity, fifteen phenolic nor-tripterpenes isolated from Celastraceae species, Maytenus jelskii, Maytenus cuzcoina, and Celastrus vulcanicola, have been studied. Their chemical structures were elucidated through spectroscopic and spectrometric techniques, resulting in the identification of three novel chemical compounds. Evaluation on human tumour cell lines (A549 and SW1573, non-small cell lung; HBL-100 and T-47D, breast; HeLa, cervix, and WiDr, colon) revealed that three compounds, named 6-oxo-pristimerol, demethyl-zeylasteral, and zeylasteral, exhibited significant activity (GI50 ranging from 0.45 to 8.6 µM) on at least five of the cell lines tested. Continuous live cell imaging identified apoptosis as the mode of action of selective cell killing in HeLa cells. Furthermore, their effect on a drug-sensitive Saccharomyces cerevisiae strain has been investigated to deepen on their mechanism of action. In dose-response growth curves, zeylasteral and 7α-hydroxy-blepharodol were markedly active. Additionally, halo assays were conducted to assess the involvement of oxidative stress and/or mitochondrial function in the anticancer profile, ruling out these modes of action for the active compounds. Finally, we also delve into the structure-activity relationship, providing insights into how the molecular structure of these compounds influences their biological activity. This comprehensive analysis enhances our understanding of the therapeutic potential of this triterpene type and underscores its relevance for further research in this field.
The social amoeba Dictyostelium discoideum is a versatile biological model widely used in drug discovery and studying cellular stress responses. However, its application for cytotoxicity evaluation of natural products, particularly algal-derived compounds, remains underutilized. In this study, we developed a high-throughput developmental assay in D. discoideum to analyze the cytotoxicity of acetone and methanol extracts from the Peruvian seaweed Glossophora kunthii. Our results showed that the acetone extract caused a transient delay in the social development of the amoeba. In contrast, the methanol extract exhibited no significant effects, even at high extract concentrations. UHPLC/Orbitrap/ESI/MS/MS analysis tentatively identified ten major compounds, including pachydictyol A and dictyotriol A diacetate. The presence of diterpenes, such as dictyotadiol and pachydictyol A, previously reported to exhibit moderate cytotoxic activity, likely explains the developmental delay observed with the acetone extract. This study highlights the utility of D. discoideum as a scalable cytotoxicity screening platform within algal pharmacognosy, facilitating the early identification of non-toxic marine natural products suitable for further biomedical and biotechnological development.
The aim of this research was to identify the wealth of secondary metabolites in the Chilean lichen Sticta caulescens, applying green chemistry approaches and comparing the following two extraction methods: (a) conventional maceration with methanol, and (b) microwave-assisted extraction (MAE) using ethyl lactate as a solvent. In addition, chemoinformatic and chemotaxonomic studies were conducted on S. caulescens and other species of the genus Sticta, which have been reported in previous studies. A UHPLC/ESI-MS/MS analysis allowed for the identification of 32 metabolites obtained from maceration and 33 from MAE, considering carbohydrates, aromatic compounds, acids, depsides, depsidones, dibenzofurans, lipids, anthraquinones, and triterpenes. Maceration using methanol yielded a slightly higher extract percentage than with ethyl lactate (6.3% versus 5.0%), while MAE extracted an almost identical spectrum of metabolites using ethyl lactate,—though including one compound detected only under MAE conditions. This highlighted both the method efficiency and selectivity. This study also incorporates a comprehensive chemoinformatic and chemotaxonomic analysis of secondary metabolites across 12 Sticta species. A computational comparison (Morgan fingerprints, Jaccard similarity, hierarchical clustering, Murcko scaffolds) demonstrated that S. caulescens is one of the most chemically diverse species, closely related to S. cordillerana, and forming part of a major chemotaxonomic lineage, which is characterized by high scaffold richness and shared aromatic/depsidone biosynthetic pathways.