Cytotoxic Alkaloids from the Whole Plants of <i>Zephyranthes candida</i>

Seven new alkaloids, <i>N</i>-methylhemeanthidine chloride (<b>1</b>), <i>N</i>-methyl-5,6-dihydroplicane (<b>5</b>), <i>O</i>-methylnerinine (<b>6</b>), <i>N-</i>ethoxycarbonylethylcrinasiadine (<b>7</b>), <i>N-</i>ethoxycarbonylpropylcrinasiadine (<b>8</b>), <i>N</i>-phenethylcrinasiadine (<b>9</b>), and <i>N</i>-isopentylcrinasiadine (<b>10</b>), together with eight known alkaloids, hemeanthamin (<b>2</b>), 3-epimacronine (<b>3</b>), (+)-tazettine (<b>4</b>), <i>N</i>-methylcrinasiadine (<b>11</b>), trisphaeridine (<b>12</b>), 5,6-dihydrobicolorine (<b>13</b>), lycorine (<b>14</b>), and nigragillin (<b>15</b>), were isolated from the whole plants of <i>Zephyranthes candida</i>. The structures of the new compounds were established by spectroscopic data interpretation, with single-crystal X-ray diffraction analysis performed on <b>1</b>. The absolute configuration of 3-epimacronine (<b>3</b>) was determined by single-crystal X-ray diffraction analysis with Cu Kα irradiation. Compounds <b>1</b>–<b>15</b> were evaluated for their in vitro cytotoxicity against five human cancer cell lines and the Beas-2B immortalized (noncancerous) human bronchial epithelial cell line. Compounds <b>1</b>, <b>2</b>, <b>9</b>, and <b>14</b> exhibited cytotoxicity with IC₅₀ values ranging from 0.81 to 13 μM with selectivity indices as high as 10 when compared to the Beas-2B cell line