Anticancer Activity of Benzomalvin Derivatives Isolated from <i>Penicillium spathulatum</i> SF7354, a Symbiotic Fungus from <i>Azorella monantha</i>

<i>Penicillium spathulatum</i> SF7354 was isolated from the extremophilic plant <i>Azorella monantha</i> collected in Chilean Patagonia and investigated for its anticancer potential. Crude extracts of SF7354 exhibited significant cytotoxic activity against multiple human cancer cell lines, with the most pronounced effect observed in HCT116 cells. Flow cytometry analysis revealed that treatment with the extract induced time-dependent apoptosis and sub-G1 accumulation, indicating activation of programmed cell death. Cell cycle analysis further showed early G0/G1 arrest, followed by a progressive increase in apoptotic populations. Western blot analysis demonstrated notable alterations in PARP and p53 protein levels, suggesting a p53-dependent mechanism of apoptosis. HPLC-based purification of the extract led to the isolation of five benzomalvin derivatives (A-E), all of which exhibited dose- and time-dependent cytotoxicity. These findings suggest that SF7354-derived benzomalvins act through apoptosis-associated mechanisms and represent promising candidates for the development of novel anticancer agents.