Extracellular Signal-Regulated Kinases (ERK) Inhibitors from <i>Aristolochia yunnanensis</i>

Six new sesquiterpenoids, aristoyunnolins A–F (<b>1</b>–<b>6</b>), an artifact of isolation [7-<i>O</i>-ethyl madolin W (<b>7</b>)], and 12 known analogues were isolated from stems of <i>Aristolochia yunnanensis</i>. The structures were determined by combined chemical and spectral methods, and the absolute configurations of compounds <b>2</b>, <b>3</b>, <b>5</b>–<b>7</b>, <b>9</b>, <b>14</b>, and <b>17</b> were determined by the modified Mosher’s method and CD analysis. Compounds <b>1</b>–<b>19</b> were screened using a bioassay system designed to evaluate the effect on mitogen-activated protein kinases (MAPKs) signaling pathways. Among three MAPKs (ERK1/2, JNK, and p38), compounds <b>1</b>, <b>4</b>, <b>10</b>–<b>13</b>, <b>16</b>, <b>18</b>, and <b>19</b> exhibited selective inhibition of the phosphorylation of ERK1/2. Compounds <b>16</b> and <b>19</b> were more active than the positive control PD98059, a known inhibitor of the ERK1/2 signaling pathway