Synthesis of bufalin derivatives with inhibitory activity against prostate cancer cells.

Bufalin possesses a strong anti-cancer effect, but the cardiac toxicity targeting the Na(+), K(+)-ATPase limits its application. Here, two bufalin derivatives, bufadienolactam (1) and secobufalinamide (2), were synthesised by treating bufalin with ammonium acetate in dimethylformamide solution. Their structures were elucidated by extensive spectroscopic methods. The structure of compound 2 was further confirmed by single-crystal X-ray diffraction analysis. Compounds 1 and 2 expressed strong inhibitory activities against androgen-dependent prostate cancer cells (IC₅₀ values about 10 μM), but only weak inhibition on Na(+), K(+)-ATPase (Ki about 70 μM), indicating that they might be potential anti-prostate cancer agents without severe cardiac toxicity.