Artemyrianolides A–S, Cytotoxic Sesquiterpenoids from <i>Artemisia myriantha</i>

Abstract

Random screening suggested that the EtOH extract of <i>Artemisia myriantha</i> (Asteraceae) and its EtOAc fraction had cytotoxicity against HepG2 cells with inhibitory ratios of 30.6% and 53.5% at 50.0 μg/mL. Bioassay-guided isolation of the most active fractions (Fr. C and Fr. D) afforded 19 new sesquiterpenolides, artemyrianolides A-S (<b>1</b>-<b>19</b>), involving 13 germacranolides (<b>1</b>-<b>13</b>), four guaianolides (<b>14</b>-<b>17</b>), and two eudesmanolides (<b>18</b> and <b>19</b>), together with 16 known sesquiterpenoids (<b>20</b>-<b>35</b>). The new compounds were characterized by physical data analyses (HRESIMS, IR, 1D and 2D NMR, ECD), and the absolute configurations of compounds <b>1</b>, <b>2</b>, and <b>11</b> were determined by X-ray crystallography. Structurally, compounds <b>2</b> and <b>11</b>-<b>13</b> maintain an uncommon <i>cis</i>-fused 10/5 bicyclic system and compound <b>12</b> possesses an unusual (7<i>S</i>) configuration. Twenty of the compounds exhibited cytotoxicity against HepG2, Huh7, and SMMC-7721 cell lines. Compound <b>9</b> showed cytotoxic activity on both HepG2 and Huh7 cells with IC₅₀ values of 8.6 and 8.8 μM, and compounds <b>8</b> and <b>33</b> showed cytotoxicity to the three human hepatoma cell lines with IC₅₀ values of 4.9 and 7.4 μM (HepG2), 4.3 and 7.8 μM (Huh7), and 3.1 and 9.8 μM (SMMC-7721), respectively.