Photodynamic antitumor activity of Ru(II) complexes of imidazo-phenanthroline conjugated hydroxybenzoic acid as the tumour targeting photosensitizers
Two novel Ru(II) polypyridyl complexes bearing imidazo-phenanthroline conjugated hydroxybenzoic acid were designed to enhance tumor targeting as the photosenistizers for photodynamic therapy. [Ru(bpy)2(phcpip)] (ClO4)2 (Ru-1) and [Ru(bpy)2(ohcpip)] (ClO4)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 activity 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.