Synthesis and biological evaluation of new pentaphyrin macrocycles for photodynamic therapy.
This paper describes the synthesis and in-depth characterization of two new porphyrogenic macrocycles 1 and 2, and provides an evaluation of these molecules as photosensitizer agents. By tuning the reaction conditions and starting from readily available 1,9-diformyl-5-phenyldipyrromethane (4) and tripyrrane dicarboxylic acid (3), both the nonaromatic isopentaphyrin 1, composed of a 24 pi-electron macrocycle, and the aromatic pentaphyrin 2, composed of a 22 pi-electron macrocycle, were obtained in good yield and purity. Confocal laser microscopy and cytofluorimetry studies showed that the newly synthesized pentaphyrins penetrate the cell membranes and localize mainly in the cytoplasm. In the absence of light, 1 and 2 exhibit a nonsignificant cytotoxic effect at concentrations up to 3 mug/mL. In contrast, the synthesized pentaphyrins, when delivered to cells at 1.5 or 3 microg/mL and irradiated with white light (8 mW/cm(2)), promoted a strong and dose-dependent phototoxic effect in four different cell lines. FACS and caspase-3/7 activation assays demonstrated that the pentaphyrins cause cell death by apoptosis.
Comuzzi
Clara
C
Department of Chemical Science and Technology, University of Udine, Via del Cotonificio 108, 33100 Udine, Italy.
Cogoi
Susanna
S
Overhand
Mark
M
Van der Marel
Gijs A
GA
Overkleeft
Herman S
HS
Xodo
Luigi E
LE
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008027:Light; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
C507818:20-phenyl-2,13-dimethyl-3,7,8,12-tetraethyl-(22)pentaphyrin; C507817:20-phenyl-2,13-dimethyl-3,7,8,12-tetraethyl-(24)isopentaphyrin; D000970:Antineoplastic Agents; D047028:Macrocyclic Compounds; D017319:Photosensitizing Agents; D011166:Porphyrins