Genearation of Halogenated Angucyclinones with Cytotoxicity Activities against Human Cancer Cell Lines Based on Biosynthesis and Chemical Conversion

The halogen substituents is critical to the structural diversity and biological activity of natural products, and the preparation of halogenated molecules has attracted much attention. In this study, we report the generation of 15 new halogenated angucyclinones by incorporating halogen-containing phenylamines into a biosynthetic C-ring-cleaved angucyclinone under mild condition. The 15 new compounds feature halogen substituents covering all four halogen atoms (F, Cl, Br, I), and some of them are hybridized halogenation products. Their structures are elucidated based on UV, IR, MS, and NMR spectroscopic analyses, expanding the structural diversity of angucyclinone-type polyketides. Cytotoxicity assays showed that 8 compounds possessed moderate cytotoxic activities against four human tumor cell lines with IC₅₀ values of 3.35 ± 0.37 to 16.02 ± 6.60 μM. These results highlight the powerful potential of combining biosynthetic and chemical methods in the generation of bioactive halogenated molecules.