Anticancer Research

Development of novel metal-based anticancer drug candidates

Cisplatin and its derivatives are used in more than 50% of the treatments for patients suffering from cancer.1 Despite their high potency and tremendous success, however, these platinum compounds have three main disadvantages: they are inefficient against platinum-resistant tumours, they are non-specific and they often have severe side effects such as nephrotoxicity. As such, alternative metal-based drugs are still desperately sought. Among the potential metal complex candidates, ruthenium complexes have emerged as one of the leading players in this field.1-4

Two complexes (i.e. NAMI-A and KP1039) are currently in clinical trial and another one (i.e. RAPTA-C) in clinical evaluation.

In this research project, novel Ru(II) complexes are synthesized, characterized and their biological activity investigated. Furthermore, the mechanism of action of these compounds is studied in depth using biochemical/molecular biological techniques as can be seen in Figure 1 with fluorescence co-localization studies of one of our Ru(II) complexes.

figure 2

Figure 1. Fluorescence co-localisation studies of a cytotoxic Ruthenium complex.

More specifically, we could recently unveil a lead compound (Figure 2).1,6 In collaboration with Dr. Stefano Ferrari from the Institute of Molecular Cancer Research and Prof. Caroline Maake from the Institute of Anatomy of the University of Zurich, we are currently investigating in-depth its mechanism of action.

cytotoxicruii complex

Figure 2. Structure of a cytotoxic Ru(II) complex developed in our labs.1


References

  1. Pierroz, V.; Joshi, T.; Leonidova, A.; Mari, C.; Schur, J.; Ott, I.; Spiccia, L.; Ferrari, S.; Gasser, G. J. Am. Chem. Soc. 2012, 134, 20376.
  2. Gasser, G.; Ott, I.; Metzler-Nolte, N. J. Med. Chem. 2011, 54, 3.
  3. Süss-Fink, G. Dalton Trans. 2010, 39, 1673.
  4. Hartinger, C. G.; Zorbas-Seifried, S.; Jakupec, M. A.; Kynast, B.; Zorbas, H.; Keppler, B. K. J. Inorg. Biochem. 2006, 100, 891.
  5. Bratsos, I.; Jedner, S.; Gianferrara, T.; Alessio, E. Chimia 2007, 61, 692.
  6. Joshi, T.; Pierroz, V.; Ferrari, S.; Gasser , G. ChemMedChem 2014, 9, 1419.