Triphenylamine-appended tri-organotin complexes: Synthesis, anticancer activities, and targeted research

Mitochondria play a crucial role in mediating apoptosis and have emerged as a promising therapeutic target for the treatment of cancer. Nevertheless, exploration of mitochondrial apoptosis as a mechanism for anticancer activity in vitro remains notably sparse. Herein, the ligands 4 ',4 '''-(phenylazanediyl)bis(([1,1 '-biphenyl]-4-carboxylic acid)) (H2L1) and 4 ',4 '''-(phenylazanediyl)bis(3-fluoro-[1,1 '-biphenyl]-4-carboxylic acid) (H2L2) were synthesized and further combined with organotin precursors and auxiliary ligands (4,4 '-bipy = 4,4 '-bipyridine, 4,4 '-bpe = 4,4 '-vinylenedipyridine) to give eight organotin complexes [(Ph3Sn)2L] (1a and 2a), [(Et3Sn)2L]n (1b and 2b), [(n-Bu3Sn)2L(4,4 '-bipy)]n (1c and 2c), [(n-Bu3Sn)2L(4,4 '-bpec)]n (1d and 2d). The complexes were characterized by X-ray single crystal diffraction, NMR (1H, 13C, and 119Sn), IR, and UV-Vis spectroscopy. The complexes exhibited strong anticancer activity against the four cancer cells and a certain degree of broad-spectrum with the IC50 ranging from 0.25 to 22.43 mu M. Furthermore, complexes 2a and 2b were selected as representatives to further investigate their anticancer mechanisms. The results suggested that these complexes could target mitochondria after cellular uptake, thereby inducing intracellular ROS production, leading to MMP collapse and activation of caspase-3, that is, these complexes potentially exert their anticancer effects through the mitochondria-mediated apoptotic pathway. Organotin(IV) complexes showed higher anti-proliferative activity towards HCT116, HeLa, HepG-2, and A549 cell lines. Anticancer studies show that complexes 2a and 2b accumulated in large amounts in the mitochondria after entering the cells, inducing mitochondrial damage, generating excessive ROS, causing a decrease in the MMP, and further releasing apoptotic factors to cause the caspase cascade reactions, which ultimately induced apoptotic cell death. image