Identification of Melampomagnolide B Derivatives as Triggers of Cuproptosis, Ferroptosis, and Apoptosis for Treatment of Lung Cancer

Herein, we described the design and synthesis of a series of melampomagnolide B-dithiocarbamate hybrids and the evaluation of their anti-lung cancer activities. The most active compound 86 (IC₅₀ = 0.46 μM) exhibited a highly potent inhibitory effect on NCI-H820 cells, with a 44-fold increase compared to the natural product melampomagnolide B (IC₅₀ = 20.43 μM). Compound 86 mediated mitochondrial dysfunction, promoted ROS generation to disrupt redox homeostasis,