title: Synthesis and characterisation of estrogenic carriers for cytotoxic Pt(II) fragments: biological activity of the resulting complexes.
abstract: This paper describes the synthesis and the spectroscopic characterisation of cis-dichloro[N-(4-(17alpha-ethynylestradiolyl)-benzyl)-ethylenediamine]platinum(II) and cis-diamino[2-(4-(17alpha-ethynylestradiolyl)-benzoylamino)-malonato]platinum(II). These complexes were synthesised in good yield according to multi-step procedures based on the classical and non-classical Sonogashira coupling reaction, respectively. These compounds retain an acceptable degree of relative binding affinity (RBA) for the alpha form of estrogen receptor. Combined treatment of breast cancer cell lines, namely hormone-sensitive MCF-7 and hormone-insensitive MDA-MB-231 cell lines, indicates that these compounds maintain agonistic activity so that the potential advantage in vehiculation of the cytotoxic moiety by means of the receptor system is counteracted by the proliferative effect of the estrogenic component of the entire molecule, especially at low concentrations.
authors.affiliation: Dipartimento di Scienze dell'Ambiente e della Vita, Università del Piemonte Orientale A. Avogadro, Spalto Marengo 33, 15100 Alessandria, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gabano
authors.forename: Claudio
authors.initials: C
authors.lastname: Cassino
authors.forename: Samuele
authors.initials: S
authors.lastname: Bonetti
authors.forename: Cristina
authors.initials: C
authors.lastname: Prandi
authors.forename: Donato
authors.initials: D
authors.lastname: Colangelo
authors.forename: Annalisa
authors.initials: A
authors.lastname: Ghiglia
authors.forename: Domenico
authors.initials: D
authors.lastname: Osella
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000138:chemical synthesis* / Q000494:pharmacology; D001665:Binding Sites; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004967:Estrogens / Q000737:chemistry*; D006801:Humans; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D009944:Organoplatinum Compounds; C506793:cis-diamino(2-(4-(17alpha-ethynylestradiolyl)-benzoylamino)-malonato)platinum; C506792:cis-dichloro(N-(4-(17alpha-ethynylestradiolyl)-benzyl)-ethylenediamine)platinum; D004958:Estradiol