Cardiac Glycosides from the Seeds of <i>Thevetia peruviana</i>

Investigation of the seeds of <i>Thevetia peruviana</i> resulted in the isolation of 15 new (<b>2</b>–<b>16</b>) and 18 known (<b>1</b> and <b>17</b>–<b>33</b>) cardiac glycosides. Eight 19-nor-cardenolides (<b>1</b>–<b>8</b>), including two rare 19-nor-10-hydroperoxycardenolides, were obtained from <i>T. peruviana</i> for the first time. All the structures were characterized by NMR spectroscopy and chemical derivatization. The inhibitory effects of cardiac glycosides <b>1</b>–<b>33</b> against three cancer cell lines (human lung cancer cells, P15; human gastric cancer cells, MGC-803; and human pancreatic cancer cells, SW1990) and one normal hepatocyte cell line, LO2, were evaluated, and a preliminary structure–activity relationship is discussed. In addition, cardiac glycosides <b>1</b>, <b>22</b>, <b>26</b>, and <b>28</b> were evaluated for their apoptosis-inducing activities in MGC-803 cells, showing IC₅₀ values in the range 0.02–0.53 μM