In vitro evaluation of rhodium and osmium RAPTA analogues: The case for organometallic anticancer drugs not based on ruthenium
In vitro evaluation of rhodium and osmium RAPTA analogues: The case for organometallic anticancer drugs not based on ruthenium
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DOI：
10.1021/om060394o
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发表时间：
2006-08-14
期刊：
影响因子：
2.8
通讯作者：
Dyson, Paul J.
中科院分区：
文献类型：
--
作者：
Dorcier, Antoine;Ang, Wee Han;Dyson, Paul J.
二聚体[（eta（5）-C5 Me 5）RhCl（mu（2）-Cl）]（2）与2或4当量的水溶性膦1，3，5-三氮杂-7-磷杂三环[3.3.1.1]癸烷（pta）反应，分别得到[Rh（eta（5）-C5 Me 5）（pta）Cl-2]和[Rh（eta（5）-C5 Me 5）（pta）（2）Cl] Cl。这两种配合物已被其特征在于在溶液中通过NMR光谱和在固体状态下通过单晶X-射线衍射，后者作为氯化物和BPh 4-盐。此外，还分别以[Rh（eta（5）-C5 Me 5）（CO）（2）]和[Rh（eta（5）-C5 H5）（PPh 3）（2）]为原料，与pta反应，制备了铑（I）配合物[Rh（eta（5）-C5 Me 5）（CO）（pta）]和[Rh（eta（5）-C5 H5）（pta）（2）]。使用HT 29结肠癌、A549肺癌和T47 D乳腺癌细胞对这些化合物以及[Os（eta（6）-C10 H14）（pta）Cl-2]和充分表征的抗转移药物[Ru（eta（6）-C10 H14）（pta）Cl-2] RAPTA-C进行体外评价。在HT 29细胞系中，与[Ru（eta（6）-C10 H14）（pta）Cl-2]最接近的两种同源物，即，[Rh（eta（5）-C5 Me 5）（pta）Cl-2]和[Os（eta（6）-C10 H14）（pta）Cl-2]表现出非常相似的细胞毒性特征。证明[Rh（eta（5）-C5 Me 5）（pta）Cl-2]在A549细胞中的细胞毒性显著更高，[Rh（eta（5）-C5 Me 5）（pta）（2）Cl] Cl在T47 D细胞中的细胞毒性高3倍，两者均相对于RAPTA-C。这些数据表明，开发基于钌的邻近元素的有机金属抗癌药物不应被忽视。
Reaction of the dimer [(eta(5)-C5Me5)RhCl(mu(2)-Cl)](2) with 2 or 4 equiv of the water-soluble phosphine 1,3,5-triaza-7-phosphatricyclo[3.3.1.1] decane (pta) affords [Rh(eta(5)-C5Me5)(pta)Cl-2] and [Rh(eta(5)-C5Me5)(pta)(2)Cl] Cl, respectively. Both complexes have been characterized in solution by NMR spectroscopy and in the solid state by single-crystal X-ray diffraction, the latter as the chloride and BPh4- salts. In addition, the rhodium(I) complexes [Rh(eta(5)-C5Me5)(CO)(pta)] and [Rh(eta(5)-C5H5)(pta)(2)] have been prepared lfrom [Rh(eta(5)-C5Me5)(CO)(2)] and [Rh(eta(5)-C5H5)(PPh3)(2)], respectively, by reaction with pta. An in vitro evaluation of these compounds, together with [Os(eta(6)-C10H14)(pta)Cl-2] and the well-characterized antimetastasis drug [Ru(eta(6)-C10H14)(pta)Cl-2], RAPTA-C, was undertaken using HT29 colon carcinoma, A549 lung carcinoma, and T47D breast carcinoma cells. In the HT29 cell line, the two nearest congeners to [Ru(eta(6)-C10H14)(pta)Cl-2], viz., [Rh(eta(5)-C5Me5)(pta)Cl-2] and [Os(eta(6)-C10H14)(pta)Cl-2], demonstrated very similar cytotoxicity profiles. [Rh(eta(5)-C5Me5)(pta)Cl-2] proved significantly more cytotoxic in A549 cells and [Rh(eta(5)-C5Me5)(pta)(2)Cl] Cl 3-fold more cytotoxic in T47D cells, both relative to RAPTA-C. These data suggest that the development of organometallic anticancer drugs based on the neighboring elements to ruthenium should not be overlooked.