Simple structural modifications confer cytotoxicity to allobetulin

A variety of allobetulin derivatives was synthesized from allobetulin or allobetulone. These compounds were screened for their cytotoxic activity using a photometric SRB assay employing six different human tumor cell lines. In summary, opening of ring A of allobetulin in general lowers the cytotoxicity, but the 2,3-seco diethyl ester was highly cytotoxic and remarkable selective for A549 lung carcinoma cells while being significantly less cytotoxic for non-malignant mouse fibroblasts. The introduction of an amino group at position C-3 in the allobetulin skeleton enhances cytotoxicity and furnishes highly cytotoxic compounds. Their selectivity to distinguish between cancer cell and non-malignant cell depends on the configuration at position C-3.