Polyoxometalates as versatile enzyme inhibitors

Polynuclear metal compounds may have considerable potential as metallic drugs. The most prominent representatives are polyoxometalates (POMs) which have been investigated since the last third of the 19th century. In addition to applications in catalysis, separation, analysis, and as electron-dense imaging agents, some of these substances have been shown to exhibit biological activity in vitro as well as in vivo ranging from anti-cancer, antibiotic, and antiviral to anti-diabetic effects.
Polyoxometalates represent a diverse ensemble of nanostructures with an almost infinite variability of chemical, physical and biological properties. The size of typical covalent bridged cluster compounds is in the range from 1 to 3 nm. The attachment of special surface groups on the periphery of cluster compounds may result in self-assembled non-covalent organized structures larger than 5 nm which are characteristic for bio-molecules, such as enzymes. Cells of mammalian organisms are typically 10 to 30 µm. However, sub-cellular organelle dimensions are smaller and range in sub-µm sizes. This comparison of size dimension illustrates that polymetalates are small enough to allow the cell membrane to be penetrated without too much interference. Evidently, some types of polyoxometalates are able to be transported into cells, particularly into mitochondria. However, many of such polyanions are only slightly taken up by cells, obviously caused by negatively charged membranes.
On the way to explore the biological activity of polynuclear cluster compounds, we recently recognised POMs as a new class of potent enzyme inhibitors. Certain polyanionic complexes are able to inhibit extracellular E-NTPDases (ecto-nucleoside triphosphate diphosphohydrolases) that are surface-located nucleotide-hydrolyzing enzymes involved in the regulation of signaling cascades by activating P2 (nucleotide) receptors.
We want to present a brief overview about the potential of POMs as E-NTPDase inhibitors and P2 receptor antagonists.