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

Lookup NU author(s): Professor Tiago OuteiroORCiD


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© The Royal Society of Chemistry 2015. 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 (logDo/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.

Publication metadata

Author(s): Nunes P, Morais GR, Palma E, Silva F, Oliveira MC, Ferreira VFC, Mendes F, Gano L, Miranda HV, Outeiro TF, Santos I, Paulo A

Publication type: Article

Publication status: Published

Journal: Organic and Biomolecular Chemistry

Year: 2015

Volume: 13

Issue: 18

Pages: 5182-5194

Online publication date: 26/03/2015

Acceptance date: 26/03/2015

ISSN (print): 1477-0520

Publisher: Royal Society of Chemistry


DOI: 10.1039/c5ob00124b

PubMed id: 25849043


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