Berners-Price S J, Girard G R, Hill D T, Sutton B M, Jarrett P S, Faucette L F, Johnson R K, Mirabelli C K, Sadler P J
Department of Chemistry, Birkbeck College, University of London, Gordon Square, UK.
J Med Chem. 1990 May;33(5):1386-92. doi: 10.1021/jm00167a017.
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.
我们报道了一系列[Au1(R2PYPR2')2]X型离子型、四面体、双螯合二膦金配合物对B16细胞的细胞毒性以及在三种可移植肿瘤模型中的抗肿瘤活性，其中Y = (CH2)2、(CH2)3或顺式-CH = CH。阴离子（X = Cl、Br、I、CH3SO3、NO3、PF6）对活性影响很小。R = R' = 苯基的配合物1、7和8 [Y = (CH2)2、(CH2)3、顺式-CH = CH，X = Cl]对P388白血病最具活性，寿命延长范围为83%至92%，对M5076肉瘤和B16黑色素瘤也有活性。带有吡啶基或氟苯基取代基的配合物活性降低。对于后者，利用19F和31P NMR来验证溶液中双螯合金(I)配合物的形成。讨论了R = Et且R' = Ph的配合物活性降低以及R = R' = Et的配合物无活性的原因，是由于它们作为还原剂的反应性增加。31P NMR研究表明，[AuI(Et2P(CH2)2PPh2)2]Cl很容易与血清、白蛋白和Cu2+离子反应生成氧化配体。
