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.