title: Lead Structures for Applications in Photodynamic Therapy. 6. Temoporfin Anti-Inflammatory Conjugates to Target the Tumor Microenvironment for In Vitro PDT.
abstract: Due to the ongoing development of clinical photodynamic therapy (PDT), the search continues for optimized photosensitizers that can overcome some of the side effects associated with this type of treatment modality. The main protagonists being: post-treatment photosensitivity, due to only limited cellular selectivity and post-treatment tumor regrowth, due to the up-regulation of pro-inflammatory agents within the tumor microenvironment. A photosensitizer that could overcome one or both of these drawbacks would be highly attractive to those engaged in clinical PDT. Certain non-steroidal anti-inflammatory drugs (NSAIDs) when used in combination with PDT have shown to increase the cytotoxicity of the treatment modality by targeting the tumor microenvironment. Temoporfin (m-THPC), the gold standard chlorin-based photosensitizer (PS) since its discovery in the 1980's, has successfully been conjugated to non-steroidal anti-inflammatory compounds, in an attempt to address the issue of post-treatment tumor regrowth. Using a modified Steglich esterification reaction, a library of "iPorphyrins" was successfully synthesized and evaluated for their PDT efficacy.
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: Luke
authors.initials: L
authors.lastname: Rogers
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: 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: Gisela M F
authors.initials: GM
authors.lastname: Vaz
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.
authors.forename: Mathias O
authors.initials: MO
authors.lastname: Senge
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D008652:Mesoporphyrins / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D059016:Tumor Microenvironment
chemical_list: D000893:Anti-Inflammatory Agents; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin