Synthesis of bufalin derivatives with inhibitory activity against prostate cancer cells

<div><p>Bufalin possesses a strong anti-cancer effect, but the cardiac toxicity targeting the Na<sup>+</sup>, K<sup>+</sup>-ATPase limits its application. Here, two bufalin derivatives, bufadienolactam (<b>1</b>) and secobufalinamide (<b>2</b>), were synthesised by treating bufalin with ammonium acetate in dimethylformamide solution. Their structures were elucidated by extensive spectroscopic methods. The structure of compound <b>2</b> was further confirmed by single-crystal X-ray diffraction analysis. Compounds <b>1</b> and <b>2</b> expressed strong inhibitory activities against androgen-dependent prostate cancer cells (IC<sub>50</sub> values about 10 μM), but only weak inhibition on Na<sup>+</sup>, K<sup>+</sup>-ATPase (<i>K</i><sub><i>i</i></sub> about 70 μM), indicating that they might be potential anti-prostate cancer agents without severe cardiac toxicity.</p></div>