Synthesis, crystal structure and antiproliferative mechanisms of gallium(iii) complexes with benzoylpyridine thiosemicarbazones

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Abstract

We have prepared six thiosemicarbazone ligands and synthesized the corresponding Ga(iii) complexes. The antitumor activity of the ligand increases with its lipophilicity, and the antitumor activity of the Ga(iii) complexes is affected by the ligands. SinceC6has the highest anticancer proliferative activity (0.14 ± 0.01 μM) against HepG-2 (Human hepatocarcinoma cell line), we characterized its structure by X-ray single crystal diffraction and explored its antiproliferation mechanism. Anti-tumor mechanism results show that Ga(iii) complex (C6) promoted HepG-2 cell cycle arrest in the G1 phase by regulating the expression of cell cycle-associated proteins (Cdk 2, cyclin A and cyclin E). Ga(iii) complex (C6) promotes apoptosis by consuming intracellular iron, enhancing intracellular reactive oxygen species (ROS), activating caspase-3/9, releasing cytochromes and apoptotic protease activating factor-1 (apaf-1).

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Qi, J., Liu, T., Zhao, W., Zheng, X., & Wang, Y. (2020). Synthesis, crystal structure and antiproliferative mechanisms of gallium(iii) complexes with benzoylpyridine thiosemicarbazones. RSC Advances, 10(32), 18553–18559. https://doi.org/10.1039/d0ra02913k

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