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Phototoxic Activity and DNA Interactions of Water‐Soluble Porphyrins and Their Rhenium(I) Conjugates
Author(s) -
Mion Giuliana,
Gianferrara Teresa,
Bergamo Alberta,
Gasser Gilles,
Pierroz Vanessa,
Rubbiani Riccardo,
Vilar Ramon,
Leczkowska Anna,
Alessio Enzo
Publication year - 2015
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201500288
Subject(s) - hela , phototoxicity , porphyrin , photodynamic therapy , chemistry , linker , photosensitizer , fluorescence , dna , cytotoxicity , selectivity , tris , intracellular , in vitro , combinatorial chemistry , stereochemistry , nucleic acid , biophysics , biochemistry , photochemistry , biology , organic chemistry , physics , quantum mechanics , computer science , catalysis , operating system
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 μ m , 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.