The [(Cp)M(CO)3] (M=Re, 99mTc) Building Block for Imaging Agents and Bioinorganic Probes: Perspectives and Limitations

• Published in: Chemistry & biodiversity Vol. 9; no. 9; pp. 1849 - 1866
• Main Authors: Can, Daniel, Peindy N'Dongo, Harmel W., Spingler, Bernhard, Schmutz, Paul, Raposinho, Paula, Santos, Isabel, Alberto, Roger
• Format: Journal Article
• Language: English
• Published: Zürich WILEY-VCH Verlag 01.09.2012; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Carbon monoxide; Congeners; Cytotoxicity; DielsAlder reaction; Histone deacetylase; Histone deacetylase (HDAC); Hydroxamic acid; Inhibitors; Labeling; Probes; Rhenium complexes; Substrates; Technetium complexes; Tumor cell lines; Tumors; X-Ray crystallography
• ISSN: 1612-1872; 1612-1880
• DOI: 10.1002/cbdv.201200076

Starting from asymmetric Thiele's acid derivatives, two different imaging probes [99mTc(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 IC50 values [μM] for these compounds, comparable to their purely organic congeners.