Faculty of Agriculture, University of Belgrade, Nemanjina 6, 11080 Belgrade-Zemun, Serbia.
Institute of Oncology and Radiology, 11000 Belgrade, Serbia.
Eur J Med Chem. 2015 Jan 27;90:766-74. doi: 10.1016/j.ejmech.2014.12.019. Epub 2014 Dec 12.
Five novel gold(III) complexes of general formulas [AuCl2{(S,S)-R2eddip}]PF6, ((S,S)-eddip = (S,S)-ethylenediamine-N,N'-di-2-propanoate, R = n-Bu, n-Pe, i-Bu, i-Am, cPe; 1-5, respectively) were synthesized and characterized by UV/Vis, IR and NMR spectroscopy and mass spectrometry. DFT calculations indicated that (R,R)-N,N'-configuration diastereoisomers were the most stable for 1-5. 3 is stable in DMSO for at least 24 h, but immediate hydrolysis in PBS occurs. 3 is readily reduced with ascorbic acid and forms adducts with bovine serum albumin (BSA). In vitro anticancer activity of the gold(III) complexes against human cervix adenocarcinoma HeLa, human myelogenous leukemia K562, human melanoma Fem-x tumor cell lines, as well as against non-cancerous human embryonic lung fibroblast cell line MRC-5 was determined using MTT assay. Complex 4 showed highest activity and selectivity (IC50(Fem-x) = 1.3 ± 0.2; IC50(MRC-5)/IC50(Fem-x) = 72.5 ± 12.4), 4 times more active and 28 times more selective than cisplatin. Complexes induced apoptotic mode of death in a time-dependent manner in HeLa cells.
五种新型金(III)配合物的通式为[AuCl2{(S,S)-R2eddip}]PF6，其中 (S,S)-eddip = (S,S)-乙二胺-N,N'-二(2-丙酸盐)，R = n-Bu，n-Pe，i-Bu，i-Am，cPe；分别为 1-5。它们通过 UV/Vis、IR 和 NMR 光谱以及质谱法进行了合成和表征。DFT 计算表明，1-5 的最稳定构象为 (R,R)-N,N'-构型非对映异构体。3 在 DMSO 中至少稳定 24 小时，但在 PBS 中立即发生水解。3 可与抗坏血酸迅速还原，并与牛血清白蛋白 (BSA) 形成加合物。采用 MTT 法测定了金(III)配合物对人宫颈腺癌 HeLa、人髓性白血病 K562、人黑色素瘤 Fem-x 肿瘤细胞系以及非癌细胞人胚肺成纤维细胞系 MRC-5 的体外抗癌活性。结果表明，4 号配合物具有最高的活性和选择性（IC50(Fem-x) = 1.3 ± 0.2；IC50(MRC-5)/IC50(Fem-x) = 72.5 ± 12.4），比顺铂活性高 4 倍，选择性高 28 倍。配合物在 HeLa 细胞中以时间依赖性方式诱导细胞凋亡。
