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Issue 18, 2015
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Isostructural Re(i)/99mTc(i) tricarbonyl complexes for cancer theranostics

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Merging classical organic anticancer drugs with metal-based compounds in one single molecule offers the possibility of exploring new approaches for cancer theranostics, i.e. the combination of diagnostic and therapeutic modalities. For this purpose, we have synthesized and biologically evaluated a series of Re(I)/99mTc(I) tricarbonyl complexes (Re1–Re4 and Tc1–Tc4, respectively) stabilized by a cysteamine-based (N,S,O) chelator and containing 2-(4′-aminophenyl)benzothiazole pharmacophores. With the exception of Re1, all the Re complexes have shown a moderate cytotoxicity in MCF7 and PC3 cancer cells (IC50 values in the 15.9–32.1 μM range after 72 h of incubation). The cytotoxic activity of the Re complexes is well correlated with cellular uptake that was quantified using the isostructural 99mTc congeners. There is an augmented cytotoxic effect for Re3 and Re4 (versusRe1 and Re2), and the highest cellular uptake for Tc3 and Tc4, which display a long ether-containing linker to couple the pharmacophore to the (N,S,O)-chelator framework. Moreover, fluorescence microscopy clearly confirmed the cytosolic accumulation of the most cytotoxic compound (Re3). Biodistribution studies of Tc1–Tc4 in mice confirmed that these moderately lipophilic complexes (log Do/w = 1.95–2.32) have a favorable bioavailability. Tc3 and Tc4 presented a faster excretion, as they undergo metabolic transformations, in contrast to complexes Tc1 and Tc2. In summary, our results show that benzothiazole-containing Re(I)/99mTc(I) tricarbonyl complexes stabilized by cysteamine-based (N,S,O)-chelators have potential to be further applied in the design of new tools for cancer theranostics.

Graphical abstract: Isostructural Re(i)/99mTc(i) tricarbonyl complexes for cancer theranostics

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Supplementary files

Article information

21 Jan 2015
26 Mar 2015
First published
26 Mar 2015

Org. Biomol. Chem., 2015,13, 5182-5194
Article type
Author version available

Isostructural Re(I)/99mTc(I) tricarbonyl complexes for cancer theranostics

P. Nunes, G. R. Morais, E. Palma, F. Silva, M. C. Oliveira, V. F. C. Ferreira, F. Mendes, L. Gano, H. V. Miranda, T. F. Outeiro, I. Santos and A. Paulo, Org. Biomol. Chem., 2015, 13, 5182
DOI: 10.1039/C5OB00124B

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