Discrete Palladium-Triggered Deprotection Chemistry for Prodrug Activation in Cancer Cells

Y.H. Tan1, R. Frédérick2, O. Riant1

1 Institute of Condensed Matter and Nanosciences (IMCN), Université catholique de Louvain

2 Louvain Drug Research Institute (LDRI), Université catholique de Louvain

email: yonghua.tan@uclouvain.be
 

Prodrugs are molecules with little or no pharmacological activity that are converted to the active parent drug in vivo by enzymatic or chemical reactions or by a combination of the two1. Prodrug strategy can be used to overcome barriers for toxicity. For example, caged doxorubicin is released into doxorubicin by metal complexes2,3.
 

In our research, using the Tsuji-Trost reaction as the chemical activation to release prodrug. As we knew, palladium complexes play an important role in this reaction. Although there were a lot of reports involved the use of palladium complexes in cellulo, most applications have been described as nanostructures4. We found few discrete palladium complexes had been used in the context of living cells. Therefore, we used the 7-amino-4-methylcoumarin (Ncoum) as probe to screen the ligands and optimize the conditions in this deprotection reaction. We found tri(2-furyl) phosphine (TFP) was the best ligand coordinating to acetanilide palladium complexes. Then, we used PdCl2(TFP)2 as reference.4 we explored that the acetanilide palladium complexes could be used in deprotection of ally carbamate in SiHa cancer cells and better than the reference. Our next step will focus on using those palladium complexes to release caged doxorubicin in cancer cells. It can become the key for minimizing overall systemic exposure and undesirable side effects.


References

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2.  Völker, T., Meggers, E. ChemBioChem. 2017, 18, 1083-1086.

3.  Stenton, B. J., Oliveira, B. L., Matos, M. J., Sinatra, L., Goncalo, J. and Bernardes, L. Chem.Sci. 2018, 9, 4185-4189.

4.  Miller, M. A., Askevold, B., Mikula, H., Kohler, R. H., Pirovich, D. and Weissleder, R. Nat. Commun. 2017, 8, 15906-15918.