Departamento de Química Inorgánica, Universidad de Murcia, Campus de Espinardo, Murcia, Spain.
J Inorg Biochem. 2011 Apr;105(4):525-31. doi: 10.1016/j.jinorgbio.2010.12.005. Epub 2010 Dec 29.
The novel steroidal carrier ligand 17-α-[4'-ethynyl-dimethylbenzylamine]-17-β-testosterone (ET-dmba 1) and the steroid--C,N-chelate platinum(II) derivatives [Pt(ET-dmba)Cl(L)] (L = DMSO (2) and PTA (3; PTA =1,3,5-triaza-7-phosphaadamantane)) have been prepared. Values of IC(50) were calculated for the new platinum complexes 2 and 3 against a panel of human tumor cell lines representative of ovarian (A2780 and A2780cisR) and breast cancers (T47D). At 48h incubation time complexes 2 and 3 show very low resistance factors (RF of <2) against an A2780 cell line which has acquired resistant to cisplatin and were more active than cisplatin (about 4-fold for 3) in T47D (AR+, AR=androgen receptor). Compound 1 retains a moderate degree of relative binding affinity (RBA=0.94%) for androgen receptors. The cytotoxicity of the non steroidal platinum analogues [Pt(dmba)Cl(L)] (dmba=dimethylbenzylamine; L=DMSO (4) and PTA (5)) has also been studied for comparison purposes. Theoretical calculations at the BP86/def2-TZVP level of theory on complex 3 have been undertaken.
新型甾体载体配体 17-α-[4'-乙炔基-二甲基苄基胺]-17-β-睾酮（ET-dmba1）和甾体-C，N-螯合铂（II）衍生物 [Pt(ET-dmba)Cl(L)]（L = DMSO（2）和 PTA（3；PTA =1,3,5-三氮杂-7-磷杂金刚烷））已被制备。针对代表卵巢癌（A2780 和 A2780cisR）和乳腺癌（T47D）的人肿瘤细胞系，计算了新铂配合物 2 和 3 的 IC50 值。在 48 小时孵育时间内，配合物 2 和 3 对获得顺铂耐药性的 A2780 细胞系的耐药因子（RF <2）非常低，并且在 T47D（AR+，AR=雄激素受体）中比顺铂更具活性（约为 3 的 4 倍）。化合物 1 对雄激素受体仍具有中等程度的相对结合亲和力（RBA=0.94%）。为了比较，还研究了非甾体铂类似物 [Pt(dmba)Cl(L)]（dmba=二甲基苄基胺；L=DMSO（4）和 PTA（5））的细胞毒性。在 BP86/def2-TZVP 理论水平上对配合物 3 进行了理论计算。
