title: Synthesis and biological evaluation of Foscan® bile acid conjugates to target esophageal cancer cells.
abstract: Porphyrins and chlorins such as Foscan® have a natural proclivity to accumulate in cancer cells. This trait has made them good candidates for photosensitizers and as imaging agents in phototherapy. In order to improve on cellular selectivity to lower post-treatment photosensitivity bile acid porphyrin bioconjugates have been prepared and investigated in esophageal cancer cells. Bile acids which are known to selectively bind to, or be readily taken up by cancer cells were chosen as targeting moieties. Synthesis of the conjugates was achieved via selective nucleophilic monofunctionalization of 5,10,15,20-tetrahydroxyphenylporphyrins with propargyl bromide followed by Cu(I) mediated cycloaddition with bile acid azides in good yields. The compounds were readily taken up by esophageal cancer cells but showed no PDT activity.
authors.affiliation: School of Chemistry, SFI Tetrapyrrole Laboratory Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse Street, Dublin 2, Ireland.
authors.forename: Luke
authors.initials: L
authors.lastname: Rogers
authors.forename: Ferenc
authors.initials: F
authors.lastname: Majer
authors.forename: Natalia N
authors.initials: NN
authors.lastname: Sergeeva
authors.forename: Edyta
authors.initials: E
authors.lastname: Paszko
authors.forename: John F
authors.initials: JF
authors.lastname: Gilmer
authors.forename: Mathias O
authors.initials: MO
authors.lastname: Senge
mesh_terms: D001647:Bile Acids and Salts / Q000737:chemistry*; D002384:Catalysis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003287:Contrast Media / Q000138:chemical synthesis / Q000633:toxicity; D003300:Copper / Q000737:chemistry; D061565:Cycloaddition Reaction; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D010293:Pargyline / Q000031:analogs & derivatives / Q000737:chemistry; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D011166:Porphyrins / Q000737:chemistry
chemical_list: D001647:Bile Acids and Salts; D003287:Contrast Media; D017319:Photosensitizing Agents; D011166:Porphyrins; D003300:Copper; D010293:Pargyline; C458239:propargyl bromide