In search of cytotoxic abietyl amides

Based on prior research findings with pentacyclic triterpenoids, it was hypothesized that (un)-substituted benzylamides would exhibit enhanced cytotoxic activity compared to parent abietic acid. Conversely, none of these compounds was cytotoxic, but (homo)-piperazinyl amides demonstrated significant cytotoxic activity across multiple cell lines, even at concentrations as low single-digit micromolar levels. Additional staining experiments revealed that the most potent compound (with an EC₅₀ value of 2.8 mM for HT29 colon carcinoma cells) primarily induced apoptosis rather than necrosis.