Study on antitumor activity of parthenolide C‐14 derivatives

Abstract In this study, two series of C ‐14 derivatives of parthenolide were designed, and synthesized 13 ester derivatives were obtained by oxidation and further esterification of their C ‐14 methyl groups. Similarly, the C ‐14‐oxidative product suffered from iodination and reacted with amino compounds to afford 3 amine derivatives. Antiproliferative test in vitro exhibited that most of the newly synthesized compounds were more potent than parthenolide toward both human non‐small cell lung cancer A549 cell line and breast cancer MDA‐MB‐231 cell line. Among them, ZA‐5 displayed a significant antiproliferative effect against A549 with an IC 50 value of 1.03 μmol L −1 and ZB‐1 had a potency almost equal to that of the positive drug Adriamycin toward MDA‐MB‐231 cells. Finally, a mechanism study showed that ZA‐5 could significantly trigger off apoptosis of A549 cells at the test concentration.