Flavonoid-based Co(II) complexes exhibit significant photocytotoxicity in visible light with minimal dark toxicity in HeLa and A549 cancer cells by generating reactive oxygen species; inducing apoptosis and accumulating in the mitochondria.

Abstract

The global concern regarding the widespread impact of cancer has prompted extensive research into the development of metal complexes as effective agents for combating this dreadful disease. Inspired by this, we have successfully synthesized and characterized six Co(II) complexes with fluorinated flavonoid ligands viz. [Co(L₁)(L₂)₂]ClO₄ (1–6) where, L₁ is monoanionic form of 3-hydroxy flavone (HF₁ in 1 and 4), 4-fluoro-3-hydroxy flavone (HF₂ in 2 and 5), 2,6-difluoro-3-hydroxy flavone (HF₃ in 3 and 6); L₂ is 1,10-phenanthroline (phen, 1–3), 2-(anthracen-1-yl)-1H-imidazo[4,5-f][1,10]phenanthroline (aip, 4–6), studied the in vitro phototriggered cytotoxicity in cancer cells (HeLa and A549) along with human immortalized lung epithelial HPL1D as normal cells. The complexes displayed substantial binding affinity (K _b = ∼10⁵ M⁻¹) for both calf-thymus DNA and human serum albumin. Complexes 1–6 showed significant photocytotoxicity in HeLa (IC₅₀ ∼3.2-23.1 µM) and A549 (IC₅₀ ∼1.1-19.0 µM) cancer cells upon visible light irradiation with low dark toxicity (IC₅₀ >100 µM). The complexes generate reactive oxygen species (ROS) viz. hydroxyl radical and singlet oxygen on exposure to visible light, which are believed to be responsible for triggering apoptosis in cancer cells in presence of visible light. Notably, complex 6 exhibits a preference for accumulating in the mitochondria of A549 cells.