Lead structures for applications in photodynamic therapy. 5. Synthesis and biological evaluation of water soluble phosphorus(V) 5,10,15,20-tetraalkylporphyrins for PDT

Aoife A Ryan; Mothi M Ebrahim; Rosine Petitdemange; Gisela M Vaz; Edyta Paszko; Natalia N Sergeeva; Mathias O Senge

doi:10.1016/j.pdpdt.2014.07.003

Lead structures for applications in photodynamic therapy. 5. Synthesis and biological evaluation of water soluble phosphorus(V) 5,10,15,20-tetraalkylporphyrins for PDT

Photodiagnosis Photodyn Ther. 2014 Dec;11(4):510-5. doi: 10.1016/j.pdpdt.2014.07.003. Epub 2014 Aug 5.

Authors

Aoife A Ryan¹, Mothi M Ebrahim¹, Rosine Petitdemange¹, Gisela M Vaz², Edyta Paszko², Natalia N Sergeeva², Mathias O Senge³

Affiliations

¹ School of Chemistry, SFI Tetrapyrrole Laboratory, Trinity Biomedical Sciences Institute, 152-160 Pearse Street, Trinity College Dublin, The University of Dublin, Dublin 2, Ireland.
² Medicinal Chemistry, Institute of Molecular Medicine, Trinity Centre for Health Sciences, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
³ School of Chemistry, SFI Tetrapyrrole Laboratory, Trinity Biomedical Sciences Institute, 152-160 Pearse Street, Trinity College Dublin, The University of Dublin, Dublin 2, Ireland; Medicinal Chemistry, Institute of Molecular Medicine, Trinity Centre for Health Sciences, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland. Electronic address: sengem@tcd.ie.

PMID: 25102162
DOI: 10.1016/j.pdpdt.2014.07.003

Abstract

Improved photosensitizers for use in photomedicine must possess good water-solubility and optimal photophysical properties. Phosphorus(V) porphyrins fulfill these criteria and are a class of porphyrins with significant potential applications in phototherapy. Five phosphorus(V) porphyrins bearing alkyl substituents have been synthesized. Reasonable to good yields were obtained for all P(V) insertions and all compounds underwent biological evaluation for their PDT activity on two esophageal cancer cell lines, OE33 and SKGT-4. Their cellular uptake was investigated using a high content screening method. Notably, three compounds displayed good uptake and using the MTS cell proliferation assay, two were shown to have photocytotoxicity comparable to mTHPC (Temoporfin(®)) with IC50 values of 6.5 and 5.5 μM.

Keywords: Cancer; Esophageal cancer; Phosphorus; Photodynamic therapy; Photosensitizers; Porphyrins.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects
Apoptosis / radiation effects
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Proliferation / radiation effects
Cell Survival / drug effects
Cell Survival / radiation effects
Esophageal Neoplasms / drug therapy*
Esophageal Neoplasms / metabolism*
Esophageal Neoplasms / pathology
Humans
Light
Photochemotherapy
Photosensitizing Agents / chemical synthesis
Photosensitizing Agents / pharmacokinetics
Photosensitizing Agents / therapeutic use
Porphyrins / chemical synthesis
Porphyrins / pharmacokinetics*
Porphyrins / therapeutic use*
Solubility
Treatment Outcome
Water / chemistry

Substances

Photosensitizing Agents
Porphyrins
Water