title: Cytotoxicity and antitumor activity of some tetrahedral bis(diphosphino)gold(I) chelates.
abstract: We report the cytotoxicity toward B16 cells and antitumor activity in three transplantable tumor models of a series of ionic, tetrahedral, bischelated gold diphosphine complexes of the type [Au1(R2PYPR2')2]X, where Y = (CH2)2, (CH2)3, or cis-CH = CH. The anion (X = Cl, Br, I, CH3SO3, NO3, PF6) had little effect upon activity. The R = R' = phenyl complexes 1, 7, and 8 [Y = (CH2)2, (CH2)3, cis-CH = CH, X = Cl] were the most active against P388 leukemia, with an increase in lifespan ranging from 83 to 92% and were also active against M5076 sarcoma and B16 melanoma. Complexes with pyridyl or fluorophenyl substituents had reduced activities. For the latter, 19F and 31P NMR were used to verify the formation of bischelated gold(I) complexes in solution. The reduced activity of the complex with R = Et and R' = Ph and inactivity with R = R' = Et are discussed in terms of their increased reactivity as reducing agents. 31P NMR studies show that [AuI(Et2P(CH2)2PPh2)2]Cl readily reacts with serum, albumin, and Cu2+ ions to give oxidized ligand.
authors.affiliation: Department of Chemistry, Birkbeck College, University of London, Gordon Square, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Berners-Price
authors.forename: G R
authors.initials: GR
authors.lastname: Girard
authors.forename: D T
authors.initials: DT
authors.lastname: Hill
authors.forename: B M
authors.initials: BM
authors.lastname: Sutton
authors.forename: P S
authors.initials: PS
authors.lastname: Jarrett
authors.forename: L F
authors.initials: LF
authors.lastname: Faucette
authors.forename: R K
authors.initials: RK
authors.lastname: Johnson
authors.forename: C K
authors.initials: CK
authors.lastname: Mirabelli
authors.forename: P J
authors.initials: PJ
authors.lastname: Sadler
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002614:Chelating Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D006046:Gold; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy; D050607:Organogold Compounds; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use; D009943:Organophosphorus Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002614:Chelating Agents; D050607:Organogold Compounds; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; C063786:bis(1,2-bis(diphenylphosphino)ethene)gold (I); C063785:bis(1,2-bis(diphenylphosphino)propane)gold (I); C050185:bis(1,2-bis(diphenylphosphino)ethane)gold(I); D006046:Gold