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  • Title: Ruthenium-porphyrin conjugates with cytotoxic and phototoxic antitumor activity.
    Author: Gianferrara T, Bergamo A, Bratsos I, Milani B, Spagnul C, Sava G, Alessio E.
    Journal: J Med Chem; 2010 Jun 24; 53(12):4678-90. PubMed ID: 20491441.
    Abstract:
    We report here two novel "extended-arms" porphyrins, TetbpyPP and TedabpyPP, in which four peripheral bpy fragments are connected to the meso positions of the macrocycle through flexible linkers of different length and hydrophilicity. We describe also the new, water-soluble, tetracationic conjugate [TedabpyPP{Ru([9]aneS3)Cl}(4)][Cl](4) (6). Compound 6 belongs to the series of cationic Ru-porphyrin conjugates 1-5, each bearing four peripheral Ru(II) half-sandwich coordination compounds, that we recently prepared as potential photosensitizing chemotherapeutic agents. The in vitro cell growth inhibition of conjugates 1-6 toward MDA-MB-231 human breast cancer cells and HBL-100 human nontumorigenic epithelial cells are reported, together with the phototoxic effects of 1, 4, and 6 on MDA-MB-231 cells. All conjugates have IC(50) values in the low micromolar range that decrease by 1 order of magnitude upon irradiation of cell cultures with visible light. The most promising compounds 1 and 6 are phototoxic at low light and drug doses.
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