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DNA interaction and photodynamic antitumor activity of transition metal mono-hydroxyl corrole
Affiliation:1. Department of Chemistry and QOPNA, University of Aveiro, 3810-193 Aveiro, Portugal;2. Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal;3. Centre of Ophthalmology and Vision Sciences, IBILI, Faculty of Medicine, University of Coimbra, Portugal;4. Center of Investigation in Environment, Genetics and Oncobiology, 3001-301 Coimbra, Portugal;5. Department of Organic and Macromolecular Chemistry, Ghent University, B-9000 Gent, Belgium;6. Departament of Chemistry, Universidade Federal de Santa Catarina, UFSC, 88040-970 Florianópolis, SC, Brazil;7. Departamento de Química, Universidade Federal de Santa Maria, UFSM, 97115-900 Santa Maria, RS, Brazil;8. CICECO Aveiro Institute of Materials, University of Aveiro, 3810–193 Aveiro, Portugal
Abstract:A series of iron(III), manganese(III) and copper(III) mono-hydroxyl corrole complexes had been prepared and well characterized by UV–vis, 1H NMR, 19F NMR and HR-MS. These metallocorroles may bind to CT-DNA through external binding mode. Metallocorrole Fe-2c exhibited significant phototoxicity and low toxicity toward A549 tumor cells. While manganese (III) and copper (III) corroles showed hypotoxicity to A549, MCF-7 and HepG-2 tumor cells, whether under dark or illumination conditions. All tested metallocorroles exhibited non-toxicity to human normal cells (GES-1) with or without irradiation at 625 nm. Cell cycle analysis indicated that metallocorrole Fe-2c arrested the cell cycle at G2/M phase and increased the Sub-G1 phase in A549 cell lines. It was mainly localized at mitochondria and could significantly reduce mitochondrial membrane potential after photodynamic treatment, which would further induce tumor cell apoptosis.
Keywords:Corrole  Transition metal complex  Photodynamic therapy  DNA-binding  Apoptosis
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