Bakalova A, Buyukliev R, Ivanova Z, Momekov G, Ivanov D
Department of Chemistry, Faculty of Pharmacy, Medical University of Sofia, Sofia, Bulgaria.
Drug Res (Stuttg). 2013 Aug;63(8):420-3. doi: 10.1055/s-0033-1345109. Epub 2013 May 15.
3 Pt(IV) complexes with 3-ethyl-5-methyl-5-(4-pyridyl)hydantoin (4), 3-propyl-5-methyl-5-(4-pyridyl)hydantoin (5) and 3-benzyl-5-methyl-5-(4-pyridyl)hydantoin (6) with general formulae cis-[Pt(L)2Cl4] were synthesized. The novel compounds were characterized by elemental analysis, IR, 1H, 13C, NMR spectra in solid state and in solution. The studies showed that the ligands coordinate to the platinum ions in a monodentate manner through the nitrogen atom from the pyridine ring. The cytotoxic activity in vitro of newly synthesized complexes as well as their previously prepared analogous of Pt(IV) with other derivatives like 3-amino-5-methyl-5-(4-pyridyl)hydantoin (1), 5-methyl-5-(4-pyridyl)hydantoin (2), 3,5-dimethyl-5-(4-pyridyl)hydantoin (3) was screened against a panel of human tumor cell lines. The tested compounds displayed cytotoxic activity which was invariably superior with the Pt(IV) complex with 3-benzyl-5-methyl-5-(4-pyridyl)hydantoin (6) causing 50% inhibition of cellular viability at micromolar concentration, though the activity of the other studied Pt(IV) complexes proved to greatly decrease in the order 5-4-3-2-1.
合成了3种通式为顺式-[Pt(L)₂Cl₄]的铂(IV)配合物,其配体分别为3-乙基-5-甲基-5-(4-吡啶基)乙内酰脲(4)、3-丙基-5-甲基-5-(4-吡啶基)乙内酰脲(5)和3-苄基-5-甲基-5-(4-吡啶基)乙内酰脲(6)。通过元素分析、红外光谱、固态和溶液状态下的¹H、¹³C核磁共振光谱对这些新型化合物进行了表征。研究表明,配体通过吡啶环上的氮原子以单齿方式与铂离子配位。针对一组人类肿瘤细胞系,筛选了新合成配合物以及它们之前制备的与其他衍生物如3-氨基-5-甲基-5-(4-吡啶基)乙内酰脲(1)、5-甲基-5-(4-吡啶基)乙内酰脲(2)、3,5-二甲基-5-(4-吡啶基)乙内酰脲(3)类似的铂(IV)配合物的体外细胞毒性活性。测试的化合物显示出细胞毒性活性,其中与3-苄基-5-甲基-5-(4-吡啶基)乙内酰脲(6)形成的铂(IV)配合物在微摩尔浓度下能导致50%的细胞活力抑制,其活性始终优于其他化合物,不过其他研究的铂(IV)配合物的活性按5-4-3-2-1的顺序大幅降低。