Jolley J N, Yanovsky A I, Kelland L R, Nolan K B
Department of Chemistry, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin.
J Inorg Biochem. 2001 Jan 15;83(2-3):91-100. doi: 10.1016/s0162-0134(00)00190-2.
Several cisplatin analogues of ethylenediamine-derived ligands containing alcohol, carboxylic acid and acetate substituents have been prepared and characterised. Oxidation of some of these square planar platinum(II) complexes using aqueous hydrogen peroxide gave octahedral platinum(IV) complexes, containing trans hydroxo ligands. Acetylation of the hydroxo ligands was achieved by reaction with acetic anhydride, giving complexes which are analogues of the antitumour drug, JM-216. Oxidation of the complex [Pt(H2L4)Cl2], where H2L4 is ethylenediamine-N,N'-diacetic acid, with H2O2 gave the platinum(IV) complex [PtL4Cl2].H2O in which L4 is tetradentate as shown by a crystal and molecular structure. This complex was previously reported to be [Pt(HL4)(OH)Cl2] in which HL4 is tridentate. Several of the complexes were tested for antitumour activity against five human ovarian carcinoma cell lines. IC50 values range from 4.0 microM for cis,trans-PtCl2(OH)2(NH2CH2CH2NHCH2CH2OH) against the CH1 cell line to >25 microM indicating moderate to low activity relative to other platinum complexes.
已经制备并表征了几种含有醇、羧酸和乙酸酯取代基的乙二胺衍生配体的顺铂类似物。使用过氧化氢水溶液氧化其中一些平面正方形铂（II）配合物，得到了含有反式羟基配体的八面体铂（IV）配合物。通过与乙酸酐反应实现羟基配体的乙酰化，得到了与抗肿瘤药物JM-216类似的配合物。用H2O2氧化配合物[Pt(H2L4)Cl2]（其中H2L4是乙二胺-N,N'-二乙酸），得到铂（IV）配合物[PtL4Cl2].H2O，晶体和分子结构表明L4是四齿的。该配合物先前报道为[Pt(HL4)(OH)Cl2]，其中HL4是三齿的。测试了几种配合物对五种人卵巢癌细胞系的抗肿瘤活性。IC50值范围从顺式、反式-PtCl2(OH)2(NH2CH2CH2NHCH2CH2OH)对CH1细胞系的4.0 microM到>25 microM，表明相对于其他铂配合物活性为中度至低度。
