Half‐sandwich Ruthenium (II) complexes with triphenylamine modified dipyridine skeleton and application in biology/luminescence imaging

Abstract

Four half-sandwich ruthenium II (Ru II ) complexes with triphenylaminemodifed dipyridine frameworks were synthesized and characterized. The cytotoxicity of target complexes toward A549 (lung cancer cells), HeLa (cervical cancer cells) and HepG2 (hepatoma cells) were obtained by the MTT assay, which were superior to cisplatin with the IC 50 values changed from 2.4 ± 0.1 μM to 9.2 ± 2.7 μM. Meanwhile, complexes possess the ability of antimetastasis to cancer cells. Ru II complexes could be transported by serum albumin, catalyze the conversion of NADH (the reduced state of nicotinamide-adenine dinucleotide) to NAD + and induce the accumulation of reactive oxygen species, which confirmed the antineoplastic mechanism of oxidation. Ru II complexes could enter A549 cells followed by a non-energy dependent cellular uptake mechanism, target lysosomes with the Pearson's colocalization coefficient of 0.75, lead to lysosomal damage, disturb the cell cycle (S phase), and eventually induce apoptosis. The results demonstrate that these Ru II complexes are potential anticancer agents with dual functions, including metastasis inhibition and lysosomal damage.

In vitro and in vivo antitumor activity of novel half-sandwich ruthenium complexes containing quinoline derivative ligands

“…[19][20][21] For example, Liu et al synthesized a series of ruthenium complexes containing different chelating ligands showing remarkable antitumor potential and organelle targeting ability, which can induce apoptosis through a mechanism different from cisplatin. 22,23 However, Ana Isabel Tomaz and workers synthesized a series of bisphosphone-containing cymene semisandwich ruthenium complexes and determined their 72 h killing activity against ovarian cancer cells (A2780) and breast cancer cells (MCF-7 and MDA-MB-231). 24 The complex exhibited excellent cytotoxicity in the submicromolar concentration range and led to cell death through apoptosis and autophagy.…”

Imidazole and Benzimidazole Modified Half-Sandwich IridiumIIIN-Heterocyclic Carbene Complexes: Synthesis, Anticancer Application, and Organelle Targeting

“…Cis-platin exerts good and broad-spectrum anticancer effects (Deubel and Lau, 2006;Romero-Canelón and Sadler, 2013;Muhammad and Guo, 2014), but, when used extensively, platinum-based drugs may promote drug resistance and instability; become insoluble in biological media; and become toxic to blood and gastrointestinal tract (Ma et al, 2014;Liu et al, 2015). Thus, various organometallic anticancer drugs, such as tin, iridium, ruthenium, and osmium anticancer complexes, have been developed (Sun and Che, 2009;Lu et al, 2015;Zeng et al, 2017;Ge et al, 2019;Li et al, 2019).…”