Organometallic compounds as new drugs? Cobalt-containing aspirin complex with potential anti-tumor properties

Jan 13, 2009

Despite considerable progress in modern chemotherapy, there remains a large demand for innovative anti-tumor agents. A new approach involves modeling the pharmacological properties of established drugs with organometallic fragments. As a team of scientists from Berlin and Bochum (Germany), Innsbruck (Austria), and Leiden (The Netherlands) report in the journal Angewandte Chemie, cobalt-aspirin complexes have potential as cytostatics.

Most drugs used today are purely organic compounds. Stimulated by the enormous success of the inorganic complex cisplatin in tumor treatment, interest in metal complexes has grown. Within cells, metal complexes can participate in reactions that are not possible with conventional organic substances.

Aspirin (acetylsalicylic acid) belongs to the family of nonsteroidal antirheumatics (NSAR), which have anti-inflammatory and pain-relieving effects. The pharmacological effects of NSARs stem from the inhibition of enzymes in the cyclooxygenase family (COX). These enzymes not only play a central role in inflammatory processes, they also seem to be involved in tumor growth. NSARs have thus come into focus as potential cytostatics. It may be possible to improve anti-tumor activity in the case of aspirin by binding it to an organometallic fragment.

Within the scope of the “Biological Function of Organometallic Compounds” research group funded by the Deutsche Forschungsgemeinshaft (German Research Foundation, DFG), the team determined that “Co-Aspirin”, a hexacarbonyldicoboalt-aspirin complex, inhibits COX activity differently to aspirin. Whereas the effect of aspirin stems from the acetylation of a serine residue in the active center of COX, Co-Asprin does not attack this side chain, instead acetylating several other sites. This may block access to the active center of the enzyme, resulting in a different activity spectrum for the drug.

Experiments with zebra fish embryos showed that in contrast to aspirin, Co-Aspirin inhibits both cell growth and the formation of small blood vessels (angiogenesis). Tumors are dependent on newly formed blood vessels for their nutrients and can be starved out by the inhibition of angiogenesis. In addition, Co-Aspirin modulates other tumor-relevant metabolic pathways. For example, it activates the enzyme caspase, which is involved in processes that lead to apoptosis (programmed cell death).

Paper: Ingo Ott, Modulation of the Biological Properties of Aspirin by Formation of Bioorganometallic Derivative, Angewandte Chemie International Edition 2009, 48, No. 6, 1160-1163, doi: 10.1002/anie.200803347

Provided by Wiley

Explore further: Active, biodegradable packaging for oily products

add to favorites email to friend print save as pdf

Related Stories

A new century of Alzheimer's disease research

Jul 25, 2007

Imagine the day when a routine visit to the family doctor includes a simple blood test to predict the risk for developing Alzheimer’s disease (AD). If the test returns a worrisome result -- too many sticky brain proteins ...

Recommended for you

Developing the battery of the future

6 hours ago

The search for the next generation of batteries has led researchers at the Canadian Light Source synchrotron to try new methods and materials that could lead to the development of safer, cheaper, more powerful, ...

Water purification at the molecular level

16 hours ago

(Phys.org) —Fracking for oil and gas is a dirty business. The process uses millions of gallons of water laced with chemicals and sand. Most of the contaminated water is trucked to treatment plants to be ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.