Discovery of new bianthrones and chlorinated bianthrones with cytotoxic activity against cancer cells from Penicillium hispanicum guided by HSQC-based DeepSAT

Three new racemic bianthrones, including two pairs of (±)-penithrones A (1) and B (2), and a chlorinated derivative (±)-penithrone C (3), along with their biogenetic precursors (4–6) were discovered from the culture extract of the mangrove-derived fungus Penicillium hispanicum LA032 using HSQC-based DeepSAT. The structural elucidation of these new compounds was achieved through comprehensive integration of NMR spectroscopy, high-resolution mass spectrometry (HRESIMS), and NMR calculations with CP3 analysis. Compounds 1 and 2 exhibited significant cytotoxic activity against HeLa, HCT116, and MCF-7 cancer cell lines, with IC₅₀ values ranging from 5.09 ± 0.65 to 9.47 ± 0.22 μmol/L. In addition, network pharmacology analysis and molecular docking studies revealed Mitogen-Activated Protein Kinase 10 (MAPK10) as a potential target of 1 for its anticancer effect.