Pyrazole appended quinoline-BODIPY based arene ruthenium complexes: their anticancer activity and potential applications in cellular imaging

Abstract

Synthesis of an entirely new series of arene ruthenium complexes [Ru(η6-C6H6)(L1)Cl]PF6, (1), [Ru(η6-C10H14)(L1)Cl]PF6 (2), [Ru(η6-C6H6)(L2)Cl]PF6 (3) and [Ru(η6-C10H14)(L2)Cl]PF6 (4) involving 5-[2-(1H-pyrazol-1-yl)quinoline]-BODIPY (L1) and 5-[6-methoxy-2-(1H-pyrazol-1-yl)quinoline]-BODIPY (L2) was described. The ligands and complexes were thoroughly characterized by various physicochemical techniques and the structures of L1, 1 and 4 were determined by X-ray single crystal analyses. Photo-/ and electrochemical property, DNA binding, cytotoxicity, cellular uptake and apoptotic studies on 1-4 were performed by various methods, while singlet oxygen-mediated cytotoxicity via photo-irradiation by visible light was supported by 1,3-diphenylisobenzofuran titration studies. Binding of the complexes in the minor groove of CT-DNA via van der Waals forces and electrostatic interactions was affirmed by molecular docking studies. In vitro antiproliferative activity and photocytotoxicity of 1-4 were examined against the human cervical cancer cell line (HeLa) which clearly showed that these are extremely photocytotoxic under visible light (400-700 nm, 10 J cm−2; IC50 49.15, 1; 25.18, 2; 15.85, 3; 12.87, 4), less toxic in the dark (IC50 > 100 μM) and preferentially accumulate in the lysosome of the HeLa cells. Further, these complexes behave as a potential theranostic agent and their ability to kill cancer cells under visible light lies in the order 4 > 3 > 2 > 1. © The Royal Society of Chemistry.