Phototoxic Activity and DNA Interactions of Water-Soluble Porphyrins and Their Rhenium(I) Conjugates.
In the search for alternative photosensitizers for use in photodynamic therapy (PDT), herein we describe two new water-soluble porphyrins, a neutral fourfold-symmetric compound and a +3-charged tris-methylpyridinium derivative, in which either four or one [1,4,7]-triazacyclononane (TACN) units are connected to the porphyrin macrocycle through a hydrophilic linker; we also report their corresponding tetracationic Re(I) conjugates. The in vitro (photo)toxic effects of the compounds toward the human cell lines HeLa (cervical cancer), H460M2 (non-small-cell lung carcinoma), and HBL-100 (non-tumorigenic epithelial cells) are reported. Three of the compounds are not cytotoxic in the dark up to 100 μm, and the fourfold-symmetric couple revealed very good phototoxic indexes (PIs). The intracellular localization of all derivatives was studied in HeLa cells by confocal fluorescence microscopy. Although low nuclear localization was observed for some of them, it still prompted us to investigate their capacity to bind both quadruplex and duplex DNA; we observed significant selectivity in the tris-methylpyridinium derivatives for G-quadruplex interactions.
Department of Chemical & Pharmaceutical Sciences, Università degli Studi di Trieste, P.le Europa 1, 34127, Trieste, Italy.
Giuliana
G
Mion
Department of Chemical & Pharmaceutical Sciences, Università degli Studi di Trieste, P.le Europa 1, 34127, Trieste, Italy. gianfer@units.it.
Teresa
T
Gianferrara
Callerio Foundation Onlus, Via A. Fleming 22-31, 34127, Trieste, Italy.
Alberta
A
Bergamo
Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. gilles.gasser@chem.uzh.ch.
Gilles
G
Gasser
Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
Vanessa
V
Pierroz
Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
Riccardo
R
Rubbiani
Department of Chemistry, Imperial College London, London, SW7 2AZ, UK. r.vilar@imperial.ac.uk.
Ramon
R
Vilar
Department of Chemistry, Imperial College London, London, SW7 2AZ, UK.
Anna
A
Leczkowska
Department of Chemical & Pharmaceutical Sciences, Università degli Studi di Trieste, P.le Europa 1, 34127, Trieste, Italy.
Enzo
E
Alessio
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry* / Q000187:drug effects*; D053837:DNA Cleavage; D004305:Dose-Response Relationship, Drug; D054856:G-Quadruplexes / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008027:Light; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity*; D011166:Porphyrins / Q000737:chemistry*; D012211:Rhenium / Q000737:chemistry*; D012995:Solubility; D013329:Structure-Activity Relationship; D014867:Water / Q000737:chemistry*
D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D011166:Porphyrins; D014867:Water; D012211:Rhenium; D004247:DNA
antitumor agents; photodynamic therapy (PDT); phototoxicity; porphyrins; rhenium