Journal
BIOORGANIC CHEMISTRY
Volume 94, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2019.103346
Keywords
Thieno[2,3-d]pyrimidin-4(3H)-one; Chalcone analogue; Cytotoxicity; Apoptosis; Mitochondrial death pathway
Funding
- 973 Project [2013CB911002]
- National Natural Science Foundation of China [31761133012, 31530016]
- Shenzhen Science and Technology Innovation Commission [JCYJ20170412113009742, JCYJ20180307182213033]
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Many natural or synthetic chalcones have potential anti-tumor activity. Here, we synthesized two series of chalcone analogues containing a thieno [2,3-cflpyrimidin-2-y] group and evaluated for their cytotoxic activity towards cultured human lung cancer A549 and colorectal HCT-116 cells. Among them, compound 8d was the most cytotoxic against HCT-116 cells, with an IC50 value of 2.65 mu M. Analyses of the phenotypic changes induced by this compound found a dose-dependent accumulation of HCT-116 cells in sub-G1 phase, indicating that compound 8d might induce apoptosis. Furthermore, we found that 8d triggered mitochondrial membrane potential depolarization, promoted reactive oxygen species formation in HCT-116 cells, and increased the percentage of early and late apoptotic cells. Finally, immunoblotting indicated that 8d increased PARP-1 and caspases 3, 7 and 9 cleavage. These data suggest that compound 8d induces apoptosis via the mitochondrial death pathway.
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