Search

To develop novel agents with anticancer activities, thirty-four new dihydroartemisinin-coumarin hybrids were designed and synthesized in this study. Those compounds were identified that had great anticancer activity against two cancer cell lines (MDA-MB-231 and HT-29). The structure-activity relationships of the derivatives were also discussed, and the results of docking analysis had shown that carbonic anhydrases IX (CA IX) was very likely to be one of the drug targets of the hybrids. Meanwhile, to clarify the mechanism of the anticancer activity of the hybrids molecule, we did further exploration in the bioactivity of the hybrids. The results had shown that these derivatives obviously inhibited proliferation of HT-29 cell lines, arrested G 0 /G 1 phase of HT-29 cells, suppressed the migration of tumor cells, and induced a great decrease in mitochondrial membrane potential leading to apoptosis of cancer cells. Interestingly, the hybrids also induced the other cell death pathway - ferroptosis. [ABSTRACT FROM AUTHOR]

Highlights: [•] Three derivatives of 25-hydroxyprotopanaxadiol are specific to inhibite the growth of human colorectal cancer cells. [•] They have lesser effect on the growth of normal primary muscle cells and spleno-lymphocytes compared with cancer cells. [•] They could induce apoptosis via activating the components of caspase-signaling pathways in HCT116 cells. [Copyright &y& Elsevier]