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).
Author: Ingo Ott, Freie Universität Berlin (Germany), http://userpage.fu-berlin.de/~ottingo/
Title: 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
Bolstering fat cells offers potential new leukemia treatment
17.10.2017 | McMaster University
Ocean atmosphere rife with microbes
17.10.2017 | King Abdullah University of Science & Technology (KAUST)
University of Maryland researchers contribute to historic detection of gravitational waves and light created by event
On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...
Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.
Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....
Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).
When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...
Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.
How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...
Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.
It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...
17.10.2017 | Event News
10.10.2017 | Event News
10.10.2017 | Event News
17.10.2017 | Life Sciences
17.10.2017 | Life Sciences
17.10.2017 | Earth Sciences