Antilung cancer activity and apoptosis mechanisms of imidazolyl acylhydrazone zinc and europium complexes with chain structures.

In this study, a novel bidentate imidazolyl acylhydrazone ligand containing an imidazolyl group was designed, and two novel complexes [ZnL(CHOH)]·NO (1) and [EuL(NO)DMF] (2) with a 1D chain structure were synthesized as expected, which shows significantly stronger anti-lung cancer activity than cisplatin. Complexes 1 and 2 effectively inhibit A549 cell proliferation by up-regulating the expression of cytochrome C, cleaved-caspase 3, and Bax, while down-regulating Pro-caspase 3 and Bcl-2 expression, thereby suppressing cell cycle progression and inducing the classical apoptotic pathway. Additionally, these complexes significantly inhibit A549 cell migration. Furthermore, they further elevate intracellular reactive oxygen species (ROS) levels and reduce mitochondrial membrane potential in A549 cells. In vivo anti-tumor evaluations show that complexes 1 and 2 significantly outperform cisplatin in inhibiting the growth of A549 subcutaneous tumors in nude mice, with no apparent damage to major organs. The results of histological examination show that complexes 1 and 2 do not cause obviously pathological damage to the main organs, which further verify their good biosafety in vivo. This study provides a research basis for the research and development of new metal-based drugs with chain structures which show high efficiency and low toxicity.