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Bioactive Natural Compounds in Triple-Negative Breast Cancer: Molecular Targets and Therapeutic Perspectives
(2026)
Emilia Jiménez-Flores
;
Reytor González, Claudia
;
Dolores Jima Gavilanes
;
Cesar Carrillo
;
Raquel Horowitz
Triple-negative breast cancer represents one of the most aggressive and therapeutically challenging subtypes of breast malignancies, characterized by marked biological heterogeneity, rapid progression, and limited targeted treatment options. Conventional therapies are frequently constrained by drug resistance, systemic toxicity, and high rates of recurrence. In this context, natural products have gained increasing attention as multifunctional agents capable of modulating several hallmarks of triple-negative breast cancer. Bioactive compounds, including polyphenols, terpenoids, alkaloids, and marine-derived molecules, exhibit pleiotropic antitumor effects by interfering with key oncogenic pathways. Importantly, these compounds have demonstrated the ability to counteract major mechanisms of therapeutic resistance, modulate the tumor immune microenvironment, and enhance the efficacy of standard chemotherapy and immunotherapy. Advances in drug delivery strategies, such as nanoparticle-based systems and tumor-targeted formulations, together with patient-specific molecular profiling, further expand the potential of these agents within personalized treatment approaches. This narrative review critically examines the role of natural compounds in targeting the hallmarks of triple-negative breast cancer and their potential synergistic use to improve therapeutic efficacy while reducing treatment-related toxicity. Overall, the integration of natural product-based strategies into precision oncology frameworks may offer more effective, less toxic, and individualized therapeutic options for this aggressive breast cancer subtype.
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Poison frog chemical defences are influenced by environmental availability and dietary selectivity for ants
(2025)
Nora A. Martin
;
Camilo Rodríguez
;
Aurora Alvarez‐Buylla
;
Katherine Fiocca
;
Colin R. Morrison
The ability to use small molecule alkaloids as defensive chemicals, often acquired via trophic interactions, has evolved in many organisms. Animals with diet-derived defences must balance food choices to maintain their defence reservoirs along with other physiological needs. Poison frogs accumulate skin alkaloids from their arthropod diet, but whether they show selectivity for specific prey remains unexplored. We investigated the role of leaf litter prey availability and dietary selectivity in shaping poison frog chemical defences along a geographic gradient. Specifically, we examined skin alkaloid composition, stomach contents and leaf litter ants in aposematic diablito frogs (Oophaga sylvatica) at five sites in north-western Ecuador and in sympatric, cryptic Chimbo rocket frogs (Hyloxalus infraguttatus) at one site. Our results show that differential availability of leaf litter ants influenced alkaloid profiles across diablito populations, and low levels of alkaloids were observed in the sympatric, ‘undefended’ Chimbo rocket frog. Ants were the primary dietary component of the defended species, while the ‘undefended’ species ate other prey categories including beetles and larvae in addition to ants. A prey selection analysis suggested that defended and ‘undefended' frogs both feed on a high proportion of specific small ant genera that naturally contain alkaloids, suggesting that selectivity for toxic prey is not restricted to classically aposematic and highly toxic species. These findings suggest that poison frogs’ use of feeding resources relative to availability may be an understudied and important selection factor in the evolution of acquired defences
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Alkaloid Profiling and Anti-Cholinesterase Potential of Three Different Genera of Amaryllidaceae Collected in Ecuador: Urceolina Rchb., Clinanthus Herb. and Stenomesson Herb.
(2024)
Luciana R. Tallini
;
Karen Acosta León
;
Raúl Chamorro
;
Edison H. Osorio
;
Jaume Bastida
Ecuador is an important center of biodiversity for the plant subfamily Amaryllidoideae, known for its important bioactive molecules. This study aimed to assess the chemical and biological potential of four different Amaryllidoideae species collected in Ecuador: Urceolina formosa, Urceolina ruthiana, Clinanthus incarnatus, and Stenomesson aurantiacum. Twenty-six alkaloids were identified in the bulb extracts of these species using GC-MS. The extract of S. aurantiacum exhibited the greatest structural diversity and contained the highest amounts of alkaloids, particularly lycorine and galanthamine. Only for this species, identification of all the alkaloids belonging to this chemical profile was not possible. Six of them remain unidentified. The potential of these three Amaryllidoideae genera against Alzheimer’s disease was then evaluated by measuring their AChE and BuChE inhibitory activity, revealing that C. incarnatus and U. formosa (from Sucumbíos province) showed the best results with IC50 values of 1.73 ± 0.25 and 30.56 ± 1.56 µg·mL−1, respectively. Molecular dynamic assays were conducted to characterize the possible interactions that occurs among 2-hydroxyanhydrolycorine and the AChE enzyme, concluded that it is stabilized in the pocket in a similar way to galanthamine. This study expands our understanding of the biodiversity of Amaryllidoideae species from Ecuador, highlighting their potential as source of chemical compounds with pharmaceutical applications.
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