Specific tetradentate copper chelators as anticancer agents
Résumé
The tetradentate monoquinoline series copper chelating agent (represented by TDMQ in abbreviation) has an efficient inhibition effect on several cancer cell lines. Wherein the compound TDMQ20 is used as one of the selective copper chelating agents and has strong cytotoxicity to non-small cell lung cancer (A549), cervical cancer HeLa and liver cancer HepG2 cells, and the in-vitro IC50 value range is 14-16 [mu] M and is lower than the IC50 value of a positive control drug 5-fluorouracil (5-FU). The TDMQ20 also shows remarkable anti-proliferative activity on HeLa cells in vitro. The mechanisms of cytotoxicity and anti-proliferative activity relate to generation of active oxygen in cells, serious damage of mitochondria and induction of apoptosis. The selectivity of the TDMQ20 on cancer cells and non-cancer human cells is higher than that of a positive control drug 5-FU. These data strongly support the selection of TDMQ20 as a candidate drug for the treatment of several human cancers.