Institute of Inorganic Chemistry, University of Zürich, Winterthurerstrasse 190, CH-8057 Zürich.
Chem Biodivers. 2012 Sep;9(9):1849-66. doi: 10.1002/cbdv.201200076.
Starting from asymmetric Thiele's acid derivatives, two different imaging probes [(99m)Tc(CO)(3)(CpR)] (R=potential targeting vector) are generated simultaneously in one-pot and from one substrate. This extends the previously introduced labeling strategy of metal-mediated retro-Diels-Alder reaction with HCp-R dimers. We demonstrate that chemically active functionalities such as hydroxamic acids are not following this labeling strategy. Adopting the principle of replacing phenyl rings by [Re(CO)(3)(Cp)] entities, potent histone deacetylase (HDAC)-inhibiting Re analogs of suberoylanlilide hydroxamic acid (SAHA; N-hydroxy-N'-phenyloctanediamide) were synthesized and characterized. Cytotoxic evaluation on different tumor cell lines revealed low IC(50) values [μM] for these compounds, comparable to their purely organic congeners.
从不对称 Thiele 酸衍生物出发，我们在一锅反应中同时生成了两种不同的成像探针 [(99m)Tc(CO)(3)(CpR)]（R=潜在的靶向配体），这种方法扩展了之前报道的利用金属介导的反-Diels-Alder 反应对 HCp-R 二聚体进行标记的策略。我们证明了具有化学活性的官能团，如羟肟酸，并不遵循这种标记策略。我们采用用 [Re(CO)(3)(Cp)] 取代芳环的原理，合成并表征了具有强组蛋白去乙酰化酶（HDAC）抑制活性的 Re 类似物，即琥珀酰亚胺基戊二酰胺（SAHA；N-羟基-N'-苯基辛二酰胺）。对不同肿瘤细胞系的细胞毒性评估显示，这些化合物的 IC50 值 [μM] 较低，与它们的纯有机同系物相当。
