Growth inhibition and anticancer activity of phenoxyartemisinin derivatives in various cancer cell lines

Cancer remains a significant global health challenge, underscoring the need for novel antineoplastic agents with improved efficacy and reduced toxicity. Artemisinin, a naturally occurring sesquiterpene lactone, and its derivatives have demonstrated promising anticancer potential. In this study, we synthesized and evaluated the anticancer activity of C-10-substituted artemisinin derivatives using the MTT assay across six cancer cell lines: DLD-1, SNU-16, MCF7, HepG2, A549, and U87. Growth inhibition 50% (GI₅₀) values were determined via nonlinear regression analysis. Among the tested compounds, 4b, 5d, 4e, and 4f exhibited potent anticancer activity, with GI₅₀ values below 0.1 μM in DLD-1 cells and below 0.18 μM in SNU-16 cells. Notably, 5d and 4e demonstrated potent inhibitory effects in U87 glioblastoma cells at concentrations as low as 0.2 μM. These compounds demonstrated broad-spectrum anticancer effects across all tested cell lines, highlighting their potential as promising candidates for further development. Furthermore, the structure-activity relationship analysis suggests that specific substitutions at the 10-position of artemisinin may significantly enhance its anticancer efficacy.