The natural product zanthosimuline and its 18 analogues were easily prepared from simple starting materials and evaluated in vitro against postharvest fruit fungal pathogens. The panel included Penicillium digitatum, Botrytis cinerea, Monilinia fructicola, and Rhizopus stolonifer; all of them causing relevant economic losses worldwide. The minimum inhibitory concentrations and minimum fungicidal concentrations of each compound were determined, and the main structure–activity relationships were established. The biological activity observed was strongly increased by maintaining the prenyl side chain of zanthosimuline in an N-demethylated derivative. In addition, the compound that is the most active in the in vitro evaluation was tested in freshly harvested peaches exhibiting a promising brown rot control profile, comparable to the commercial agent carbendazim but demonstrating less toxicity against human liver cell lines.

Wnt/β-catenin/T cell factor (TCF) pathway is activated in several types of human cancers, promoting cell growth and proliferation. Forkhead box containing protein class O (FOXO) transcription factors compete with TCF for β-catenin binding, particularly under cellular oxidative stress conditions. Contrary to β-catenin/TCF, β-catenin/FOXO promotes the transcription of genes involved in cell cycle arrest and apoptosis. We have previously demonstrated that in vivo interferon-α2b (IFN-α2b) administration induces apoptosis in preneoplastic livers, a mechanism mediated by reactive oxygen species (ROS) and transforming growth factor-β₁ (TGF-β₁). This study was aimed to assess the status of the Wnt/β-catenin/TCF pathway in a very early stage of rat hepatocarcinogenesis and to further evaluate the effects of in vivo IFN-α2b treatment on it. We demonstrated that the Wnt/β-catenin/TCF pathway is activated in preneoplastic rat livers. More important, in vivo IFN-α2b treatment inhibits Wnt/β-catenin/TCF pathway and promotes programed cell death possibly providing a link with FOXO pathway.