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Design, DNA Interaction and Biological Function of Cell Selective Cytotoxic Rh(iii)Compounds
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A systematic study of transition metal polypyridyl RhIII complexes of the type fac-[RhCl(pp)(L3)]2+ with facial coligands (L3 = [9]aneS3, tpm and pp = bpy, bpm, phen, tap, dpq, dppz) was performed. Structure-activity relationships related to DNA interactions and cytotoxicity have been established. Interactions of the cytotoxic polypyridyl complexes with DNA were investigated by viscosity, NMR, CD and UV/Vis spectroscopy. Photoinduced plasmid cleavage demonstrate the light induced or enhanced activity potential of the drugs. Covalent peptide interactions were determined by ESI-MS/MS. IC50 values toward the cancer cells MCF-7 and HT-29 as well as toward the human embryonic kidney cells HEK-293 were determined using the crystal violet assay. An analogous IC50 test towards HEK-293 cells was established. Apoptosis measurements were performed for non-adherent BJAB lymphoma cells and healthy leukocyte cells which established a high degree of cell selectivity for specific complexes.
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