Cell nucleus localization and high anticancer activity of quinoline-benzopyran rhodium(III) metal complexes as therapeutic and fluorescence imaging agents.

Four novel rhodium(III) complexes, [RhIII(QB1)Cl3(DMSO)] (RhN1), [RhIII(QB2)Cl3(CH3OH)]·CH3OH (RhN2), [RhIII(QB3)Cl3(CH3OH)]·CH3OH (RhS), and [RhIII(QB4)Cl3(DMSO)] (RhQ), bearing quinoline-benzopyran ligands (QB1-QB4) were synthesized and used to develop highly anticancer therapeutic and fluorescence imaging agents. Compared with the QB1-QB4 ligands (IC50 > 89.2 ± 1.7 μM for A549/DDP), RhN1, RhN2, RhS and RhQ exhibit selective cytotoxicity against lung carcinoma cisplatin-resistant A549/DDP (A549CDDP) cancer cells, with IC50 values in the range of 0.08-2.7 μM. The fluorescent imaging agent RhQ with the more extended planar QB4 ligand exhibited high anticancer activity in A549CDDP cells and was found in the cell nucleus fraction, whereas RhS had no fluorescence properties. RhQ and RhS may trigger cell apoptosis by causing DNA damage and initiating the mitochondrial dysfunction pathway. Furthermore, RhQ has a higher antitumor efficacy (ca. 55.3%) than RhS (46.4%) and cisplatin (CDDP, 33.1%), and RhQ demonstrated significantly lower toxicity in vivo than CDDP, making it a promising Rh(III)-based anticancer therapeutic and fluorescence imaging agent.