Glycol porphyrin derivatives as potent photodynamic inducers of apoptosis in tumor cells.

Abstract

The design and synthesis of glycol-functionalized porphyrins that contain one to four low molecular weight glycol chains that are linked via ether bonds to the meta-phenyl positions of meso-tetraphenylporphyrin and the comparison of fluorinated and nonfluorinated para derivatives are reported. The cellular uptake and photodynamic activity significantly depend on terminal groups of the glycol substituent. Hydroxy glycol porphyrins, in contrast with methoxy glycol porphyrins, show efficient intracellular transport and a high induction of apoptosis in tumor cell lines in vitro . Furthermore, the ethylene glycol chain at the meta position exhibits a superior efficacy that leads to the permanent ablation of human breast carcinoma (MDA-MB-231) in nude mice. In addition, fluorination enhanced the photosensitizing potential of para-phenyl derivatives. The analysis of the cell-death mechanism revealed that glycol-functionalized porphyrins represent novel nonmitochondrially localized photosensitizers that have a profound ability to induce apoptosis in tumor cells that act upstream of caspase activation. The strong interaction with a tumor marker (sialic acid) indicates the preferential association of these compounds with tumor cells.

• Authors: Jarmila Králová, Tomás Bríza, Irena Moserová, Bohumil Dolenský, Petr Vasek, Pavla Poucková, Zdenek Kejík, Robert Kaplánek, Pavel Martásek, Michal Dvorák, Vladimír Král
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 51 Issue 19 Pg. 5964-73 (Oct 09 2008) ISSN: 1520-4804 [Electronic] United States
• PMID: 18788727 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Glycols
• Porphyrins

Topics

• Animals
• Antineoplastic Agents (administration & dosage, chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Drug Design
• Drug Screening Assays, Antitumor
• Flow Cytometry
• Glycols (administration & dosage, chemistry, pharmacology)
• Humans
• Injections, Intravenous
• Mice
• Mice, Nude
• Molecular Structure
• Molecular Weight
• Neoplasms, Experimental (drug therapy)
• Photochemotherapy (methods)
• Porphyrins (administration & dosage, chemistry, pharmacology)
• Stereoisomerism
• Time Factors
• Xenograft Model Antitumor Assays