Phenanthroline Derivatives with Improved Selectivity as DNA‐Targeting Anticancer or Antimicrobial Drugs

Abstract Phenanthroline derivatives are of interest due to their potential activity against cancer, and viral, bacterial, and fungal infections. In a search for highly specific antitumor and antibacterial compounds, we report the activities of 1,10‐phenanthroline‐5,6‐dione (phendione or L 1 ), dipyrido[3,2‐ a :2′,3′‐ c ]phenazine (dppz or L 2 ), and their corresponding platinum complexes ([PtL 1 Cl 2 ] and [PtL 2 Cl 2 ]), and provide the solid‐state 3D structure for [PtL 1 Cl 2 ]. It is generally known that a toxic metal ion coordinated to an active organic moiety leads to a synergistic effect; however, we report herein that the platinum complexes [PtL 1 Cl 2 ] and [PtL 2 Cl 2 ] have weaker activities relative to those of the free ligands, especially against bacteria. Testing these agents against a variety of human cancer cell lines revealed that L 1 and [PtL 1 Cl 2 ] were at least as active as cisplatin against several of the cell lines (including a cisplatin‐resistant cell line). The absence of antibacterial activity of [PtL 1 Cl 2 ] removes the detrimental effect of phenanthrolines toward intestinal flora, suggesting a highly promising new strategy for the development of anticancer drugs with reduced side effects.