Book of Abstracts - Ruhr-Universität Bochum

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ISBOMC `10 5.7 – 9.7. 2010 Ruhr-Universität Bochum
Asborin Meets Titanium
Matthias Scholz a and Evamarie Hey-Hawkins* a
a Universität Leipzig, Institute of Inorganic Chemistry, Johannisallee 29, D-04103 Leipzig, Germany,
E-mail: mscholz@chemie.uni-leipzig.de
Asborin, the carbaborane analogue of aspirin ® , is one of the few examples in which carbaboranes are
used as phenyl-mimetic pharmacophores. Asborin was synthesised in a high-yield procedure starting
from ortho-carbaborane. The compound proved to inhibit both cyclooxygenase (COX) isozymes, the
target enzymes of aspirin. 1 The COX inhibition potential, however, was lower compared to aspirin and
the general pharmacological profile was also different to that of aspirin. Integration of the cluster in
place of the phenyl ring turned aspirin into a more toxic compound, which triggers apoptosis
pathways. Asborin was cytotoxic toward several cancer cell lines and exhibited the lowest potency
toward healthy fibroblasts. This behaviour made the carbaborane compound interesting for anticancer
drug development. As the IC50 values obtained from the cytotoxicity assays were higher than those of
commercial chemotherapeutic agents, the compound requires further fine-tuning of its cytotoxic
profile.
A promising approach to increase the antitumour activity of asborin is combination with another
cytotoxic moiety. Therefore, we decided to modify asborin with titanium complexes, as some
derivatives were found to be active toward several tumour cells. The most prominent anticancer
titanium derivatives are the organometallic compound titanocene dichloride and the bioinorganic
complex budotitane. 2 The carboxyl group and carbaborane moiety of asborin allow it to form both
bioinorganic and organometallic titanium compounds. Coordination of asborin as carboxylate could
displace the chloride ions in titanocene dichloride. Alternatively, instead of a cyclopentadienyl ring the
nido carbaborane cluster can act as ligand for titanium. Thus, carbaboranes can easily be deboronated
to give anionic nido clusters, which feature an open pentagonal plane. These anions can then form
different metallocene analogues.
References
1. M. Scholz, K. Bensdorf, R. Gust, E. Hey-Hawkins, ChemMedChem. 2009, 4, 746-748.
2. J. C. Dabrowiak: Titanium compounds for treating cancer in Metals in Medicine; 1. Ed.; Wiley:
New York, USA, 2009; pp. 167-177.
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