WHN-11, an amino-Artemisinin derivative, exhibits anticancer activity against various cancer cell lines. It depletes cellular ATP, activates autophagy, and triggers apoptosis. WHN-11 disrupts cellular protein homeostasis pathways, inducing mitochondrial fission and dysfunction. Its anticancer effects are not associated with the generation of reactive oxygen species. WHN-11 is applicable for studies on triple-negative breast cancer (TNBC).

WHN-11 demonstrates significant cytotoxicity toward several cancer cell lines, including HCC1937 (IC 50 = 0.74 μM), HCC70 (0.19 μM), MDA-MB-231 (0.5 μM) triple-negative breast cancer cells, HeLa cervical cancer cells (0.84 μM), U87 glioblastoma cells (6.57 μM), 501mel melanoma cells (0.2 μM), and HCT116 colon cancer cells (0.44 μM). It inhibits tumor sphere formation in HCC1937 triple-negative breast cancer cells. WHN-11 (5-80 μM, 9 days) significantly reduces colony formation of HCC1937 cells in a dose-dependent manner. Additionally, WHN-11 (1-50 μM, 24 h) promotes caspase-3 cleavage without affecting RARP-1 in a dose-dependent fashion. WHN-11 does not alter the levels of ROS and NQO1 mRNA within HCC1937 cells but disrupts protein homeostasis, including ubiquitination and proteasome degradation. Moreover, WHN-11 (0.1-40 μM, 1-16 h) activates apoptotic and autophagy signaling pathways in HCC1937 cells and induces mitochondrial stress and dysfunction with concentrations between 1-50 μM.