Targeted photocytotoxicity by copper(II) complexes having vitamin B6 and photoactive acridine moieties

•The copper(II) acridine conjugates are remarkably PDT active in visible light.•The complexes are efficient photo-cleavers of plasmid DNA in UV-A and red light.•Flow cytometry of the active complex shows ROS generation upon light exposure.•Confocal microscopy shows cytosolic localization of complex 1 in HeLa cells.•The complex having vitamin-B6 moiety shows selectivity towards cancer cells.

Copper(II) pyridoxal Schiff base complexes [Cu(L1/L2)(B)]ClO4 (1–4), where HL1 is 4-(((2-(1H-imidazol-4-yl)ethyl)imino)methyl)-5-(hydroxymethyl)-2-methylpyridin-3-ol (in 1 and 2), HL2 is 2-(((2-(1H-imidazol-4-yl)ethyl)imino)methyl)phenol (in 3, 4), B is 11-(9-acridinyl)dipyrido[3,2-a:2′,3′-c]phenazine (acdppz in 1 and 3), dipyrido[3,2-a:2′,3′-c]phenazine (in 2) and 1,10-phenanthroline (in 4), were synthesized, characterized and their photocytotoxicity in visible light, intracellular localization, cellular uptake and DNA photocleavage activity were studied. Complex 4 was characterized by X-ray crystallography. Complexes 1 and 3 having acdppz as photosensitizer showed significant photocytotoxicity in visible light in HeLa and MCF7 cells giving IC50 value of <0.6 μM, while being relatively non-toxic in dark. The complexes were non-toxic to non-tumorigenic HPL1D cells both in light and dark conditions. Complex 1 showed significant localization in the cytoplasm of HeLa cells within 4 h of treatment, as evidenced from confocal microscopy. DCFDA assay on 1 suggested generation of intracellular reactive oxygen species in HeLa cells upon photo-exposure. Importantly, Annexin-V-FITC/PI assay indicated photo-induced apoptotic cell death.

Graphical abstractTernary copper(II) complex of acridinyldipyridophenazine and vitamin B6-derived Schiff base showed significant PDT effect in HeLa and MCF-7 cancer cells with cytosolic localization, apoptotic cell death by photo-generated ROS and less toxicity in non-tumorous HPL1D cells.Figure optionsDownload full-size imageDownload as PowerPoint slide