title: Convergent synthesis of a steroidal antiestrogen-mitomycin C hybrid using "click" chemistry.
abstract: A convergent synthesis of a novel estrogen receptor-targeted drug hybrid was developed based on structures of the potent anti-proliferative mitomycin C and the steroidal anti-estrogen RU 39411. The steroidal antiestrogen was prepared with an azido-triethylene glycoloxy linker while the mitomycin C derivative (porfirimycin) incorporated a complementary 7-N-terminal alkyne. The two components were ligated using the Huisgen [3 + 2] cycloaddition ("click") reaction. Preliminary biological assays demonstrated that the final hybrid compound retained both potent anti-estrogenic and anti-proliferative activities.
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA, USA. r.hanson@neu.edu
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hanson
authors.forename: Edward
authors.initials: E
authors.lastname: Hua
authors.forename: David
authors.initials: D
authors.lastname: Labaree
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hochberg
authors.forename: Kyle
authors.initials: K
authors.lastname: Proffitt
authors.forename: John M
authors.initials: JM
authors.lastname: Essigmann
authors.forename: Robert G
authors.initials: RG
authors.lastname: Croy
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D057930:Click Chemistry; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D005260:Female; D006801:Humans; D016685:Mitomycin / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000903:Antibiotics, Antineoplastic; D004965:Estrogen Antagonists; C060411:RU 39411; D004958:Estradiol; D016685:Mitomycin