Abstract
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)] (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 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology*
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Apoptosis / drug effects
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Cell Cycle / drug effects
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Cell Line
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Cell Proliferation / drug effects
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Coordination Complexes / chemical synthesis
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Coordination Complexes / chemistry
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Coordination Complexes / pharmacology*
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Drug Screening Assays, Antitumor
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Humans
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Hydroxybenzoates / chemistry
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Hydroxybenzoates / pharmacology
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Imidazoles / chemistry
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Imidazoles / pharmacology
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Materials Testing
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Molecular Conformation
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Molecular Docking Simulation
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Phenanthrolines / chemistry
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Phenanthrolines / pharmacology
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Photochemotherapy*
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Photosensitizing Agents / chemical synthesis
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Photosensitizing Agents / chemistry
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Photosensitizing Agents / pharmacology*
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Reactive Oxygen Species / analysis
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Reactive Oxygen Species / metabolism
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Ruthenium / chemistry
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Ruthenium / pharmacology
Substances
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Antineoplastic Agents
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Coordination Complexes
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Hydroxybenzoates
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Imidazoles
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Phenanthrolines
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Photosensitizing Agents
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Reactive Oxygen Species
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Ruthenium
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phenolic acid