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Build It Solibri Model Checker. 4.1.Potent tumour cytotoxicity of novel amphiphilic porphyrins.
We report herein the syntheses and studies of tumour cytotoxic properties of some novel amphiphilic porphyrins. Three porphyrins, D1, P1 and P2 were synthesised. D1 is water-soluble and has an amphiphilic character, while P1 and P2 have amphiphilic character. All porphyrins showed an excellent level of cytotoxicity against human nasopharyngeal tumour KB and breast tumour MCF-7 cells. The cytotoxic mechanisms of these porphyrins in both cell lines were investigated. Our results suggest that all porphyrins are able to bind to DNA, with P1 and P2 binding preferentially to the minor groove. Porphyrin-DNA binding with P1 and P2 gave rise to higher levels of damage to DNA, reflected by the formation of large amount of free radical generation. Furthermore, all these porphyrins caused significant cell cycle arrest in the S-phase at sub-IC(50) concentrations, as measured by flow cytometry, and this was associated with massive apoptotic cell death. DNA fragmentation assay revealed that KB cells were significantly more sensitive to these novel porphyrins than MCF-7 cells. In addition, these porphyrins have a very low level of toxicity on normal human embryonic lung fibroblast (MRC5) cells.Europe: Sea of Marmara
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