title: Ruthenium-porphyrin conjugates with cytotoxic and phototoxic antitumor activity.
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.
authors.affiliation: Department of Pharmaceutical Sciences, P.le Europa 1, University of Trieste, 34127 Trieste, Italy.gianfer@units.it
authors.forename: Teresa
authors.initials: T
authors.lastname: Gianferrara
authors.forename: Alberta
authors.initials: A
authors.lastname: Bergamo
authors.forename: Ioannis
authors.initials: I
authors.lastname: Bratsos
authors.forename: Barbara
authors.initials: B
authors.lastname: Milani
authors.forename: Cinzia
authors.initials: C
authors.lastname: Spagnul
authors.forename: Gianni
authors.initials: G
authors.lastname: Sava
authors.forename: Enzo
authors.initials: E
authors.lastname: Alessio
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008027:Light; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012428:Ruthenium; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D017319:Photosensitizing Agents; D011166:Porphyrins; D012428:Ruthenium