Photodynamic antitumor activity of Ru() complexes of imidazo-phenanthroline conjugated hydroxybenzoic acid as tumor targeting photosensitizers

Two novel Ru( ii ) polypyridyl complexes bearing imidazo-phenanthroline conjugated hydroxybenzoic acid groups were designed to enhance the tumor targeting ability as photosensitizers for photodynamic therapy. [Ru(bpy) 2 (phcpip)] (ClO 4 ) 2 ( Ru-1 ) and [Ru(bpy) 2 (ohcpip)] (ClO 4 ) 2 ( Ru-2 ) (bpy = 2,2′-bipyridine; phcpip = 2-(3-carboxyl-4-hydroxyphenyl) imidazo [4,5- f ]phenanthroline; ohcpip = 2-(2-hydroxyl-3-carboxyphenyl) imidazo [4,5- f ] [1,10] phenanthroline) were synthesized and their photodynamic antitumor activities were investigated. Both complexes displayed high photocytotoxicity toward cancerous cell lines HepG2, A549, MCF-7, and MDA-MB-231, but low photocytotoxicity toward normal cell lines GES-1 and Huvec. They were mainly localized at the nucleus of HepG2 cells after 24 h incubation, arrested the cell cycle at the G2/M phase and induced cancer cell apoptosis through reactive oxygen species (ROS) mediated pathways. Tumor targeting of the complexes is attributed to stronger molecular binding to DNA. Two Ru( ii ) polypyridyl complexes bearing hydroxybenzoic acid groups exhibited high phototoxicity toward tumor cells.