title: Lead structures for applications in photodynamic therapy. 5. Synthesis and biological evaluation of water soluble phosphorus(V) 5,10,15,20-tetraalkylporphyrins for PDT.
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.
authors.affiliation: School of Chemistry, SFI Tetrapyrrole Laboratory, Trinity Biomedical Sciences Institute, 152-160 Pearse Street, Trinity College Dublin, The University of Dublin, Dublin 2, Ireland.
authors.forename: Aoife A
authors.initials: AA
authors.lastname: Ryan
authors.affiliation: School of Chemistry, SFI Tetrapyrrole Laboratory, Trinity Biomedical Sciences Institute, 152-160 Pearse Street, Trinity College Dublin, The University of Dublin, Dublin 2, Ireland.
authors.forename: Mothi M
authors.initials: MM
authors.lastname: Ebrahim
authors.affiliation: School of Chemistry, SFI Tetrapyrrole Laboratory, Trinity Biomedical Sciences Institute, 152-160 Pearse Street, Trinity College Dublin, The University of Dublin, Dublin 2, Ireland.
authors.forename: Rosine
authors.initials: R
authors.lastname: Petitdemange
authors.affiliation: Medicinal Chemistry, Institute of Molecular Medicine, Trinity Centre for Health Sciences, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Gisela M
authors.initials: GM
authors.lastname: Vaz
authors.affiliation: Medicinal Chemistry, Institute of Molecular Medicine, Trinity Centre for Health Sciences, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Paszko
authors.affiliation: Medicinal Chemistry, Institute of Molecular Medicine, Trinity Centre for Health Sciences, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Natalia N
authors.initials: NN
authors.lastname: Sergeeva
authors.affiliation: 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.
authors.forename: Mathias O
authors.initials: MO
authors.lastname: Senge
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008027:Light; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use; D011166:Porphyrins / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D012995:Solubility; D016896:Treatment Outcome; D014867:Water / Q000737:chemistry
chemical_list: D017319:Photosensitizing Agents; D011166:Porphyrins; D014867:Water
keywords: Cancer; Esophageal cancer; Phosphorus; Photodynamic therapy; Photosensitizers; Porphyrins