ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
KL4. Ruthenium Anticancer Compounds: Challenges and Expectations
E. Alessio a , I. Bratsos a , T. Gianferrara b
a
Chemical Sciences, University of Trieste, Via L. Giorgieri 1, 34127, Trieste, Italy
e-mail: alessi@units.it
b
Pharmaceutical Sciences, University of Trieste, Piazzale Europa 1, 34127, Trieste, Italy
e-mail: gianfer@units.it
Since several years the authors have been involved in the development of anticancer Ru-dmso complexes [1, 2].
The most advanced representative in this series is the Ru(III) compound NAMI-A which is selectively active
against metastases of solid tumors and has successfully accomplished a phase I clinical study on humans.
In general, ruthenium anticancer compounds can be divided in two main classes: one in which ruthenium has a
structural role, i.e. it is instrumental in determining the shape of the compound, and another in which ruthenium
has a functional role. Functional ruthenium compounds must have at least one coordination position available for
binding to the biological target. Most commonly, they are prodrugs and are activated by hydrolysis. NAMI-A is
believed to belong to this class. Conversely, structural ruthenium compounds must be stable and inert: ruthenium
itself will not make any coordination bond with the biological target, but the compound as a whole is expected to
give supramolecular interactions with the target (e.g. Coulombic, hydrogen bonding, p-p stacking, ...). Some
compounds may belong to both classes, i.e. ruthenium can make coordination bonds (functional role) and it can
give additional supramolecular interactions with the target (e.g. through its appropriately positioned ancillary
ligands, structural role). There are also other, less likely, possibilities in which ruthenium acts as a catalyst or as
a carrier for biologically active ligands that are delivered in vivo.
After a general introduction, the lecture will give an update of the clinical status of NAMI-A and then will focus
on new classes of Ru compounds that were developed more recently in the attempt to find new active species
and establish some general structure-activity relationships [3, 4].
References:
[1] E. Alessio, G. Mestroni, A. Bergamo, G. Sava In Metal Ions in Biological Systems, Volume 42: Metal Ions
and Their Complexes in Medication and in Cancer Diagnosis and Therapy; Sigel, A., Sigel, H., Eds.; M. Dekker:
New York, 2004; pp. 323-351.
[2] E. Alessio, G. Mestroni, A. Bergamo, G. Sava, G. Curr. Topics Med. Chem. 2004, 4, 1525-1535.
[3] I. Bratsos, A. Bergamo, G. Sava, T. Gianferrara, E. Zangrando, E. Alessio J. Inorg. Biochem. 2008, 102, 606-
617.
[4] I. Bratsos, S. Jedner, A. Bergamo, G. Sava, T. Gianferrara, E. Zangrando, E. Alessio J. Inorg. Biochem.
2008, 102, 1120-1133.
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