Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Inflammation: Attack is not always the best defense

27.05.2014

Pharmacists at Jena University develop three new drug candidates against inflammation

It is something like the police force of our body: the immune system. It disables intruding pathogens, it dismantles injured tissue and boosts wound healing. In this form of 'self-defense' inflammatory reactions play a decisive role.


Pharmacists at Jena University search for new drugs against inflammation.

photo: Jan-Peter Kasper/FSU

But sometimes the body’s defense mechanism gets out of control and cells or tissues are affected: “Then excessive reactions can occur and illnesses along with them,” Prof. Dr. Oliver Werz of the Friedrich Schiller University Jena says. He gives asthma, rheumatism, arteriosclerosis and cancer as examples: “For many of these diseases there are only few effective therapies without severe side effects.”

But the team of researchers working together with the Jena pharmacist has now developed three active agents which may be able to improve the healing of inflammatory illnesses better in future. The scientists present the potential therapeutic agents in renowned scientific journals. The agents are able to suppress a key enzyme in the body’s own cascade of inflammation.

“The enzyme called 5-LOX plays a pivotal role in the synthesis of so-called leukotrienes, which are part of numerous immunological and inflammatory processes,” Prof. Werz explains. Hence, the effort to prevent the synthesis of leukotrienes has been the focus of international research for inflammatory therapy for a long time. “Thousands of publications on the subject have emerged in the last 30 years,” says Werz. But apart from one exception none of these efforts have made it to the stage of an approved medication. Either the efficacy of the substances was poor or they were accompanied by unwanted side effects.

As a reason behind this, the Jena pharmacist sees the insufficient understanding of cellular regulation of the leukotriene biosynthesis and the lack of knowledge of the molecular mechanisms of agent and target molecule. “Instead of testing a number of substances to see if one of them might show any activity, we took a close look at 5-LOX and tried to find where exactly this enzyme is vulnerable and what the agents, which can interact with our target molecule, should look like," Werz describes the basis-orientated approach.

In this way the scientists of the Jena University together with partners from Austria, Italy, Turkey and Greece, were able to identify three possible agents. So for instance, a so-called benzoquinone proved to be an effective inhibitor of the 5-LOX. This is a substance which is derived from the natural product embelin from the "False Black Pepper“-plant (Embelia ribes). The pharmacists were able to show that this substance fits exactly into the active center of the enzyme and thus blocks its function. “This specifically only happens with 5-LOX," Werz says and stresses that benzoquinone may practically show no side effects.

A related substance of the red-violet natural dye indirubin, called 6-BIO, proved to be similarly promising. For this substance, the Jena researchers were able to clarify the mechanism of action as well: the 6-BIO inhibits the enzyme 5-LOX by blocking receptor sites for other molecules which are necessary for it to work properly. “In addition, 6-BIO also intervenes with the synthesis of additional inflammatory factors – the cytokines implying additional synergistic effects." This is why 6-BIO could for instance be of interest for the therapy of Alzheimer’s disease, in which cytokines are also playing a role.

The third possible active agent from the Jena University’s laboratory does not inhibit the 5-LOX itself, but it deactivates a helper-protein, which the enzyme needs for its effectiveness within the cell. The researchers identified this active agent, a benzimidazole with the short term BRP-7, by a virtual screening in a library consisting of nearly three million substances. "From our point of view all three of the drug candidates are very well suited to a further development as medications,” Prof. Werz summarizes. However, for this, the support of the pharmceutical industry is needed.

Original Publications:
Schaible AM et al. Elucidation of the molecular mechanism and the efficacy in vivo of a novel 1,4-benzoquinone that inhibits 5-lipoxygenase. British Journal of Pharmacology 2014 (DOI:10.1111/bph.12592)
Pergola C et al. Indirubin core structure of glycogen synthase kinase-3 inhibitors as novel chemotype for intervention with 5-lipoxygenase. Journal of Medical Chemistry 2014 (DOI:10.1021/jm401740w)
Pergola C et al. The novel benzimidazole derivative BRP-7 inhibits leukotriene biosynthesis in vitro and in vivo by targeting 5-lipoxygenase-activating protein (FLAP). British Journal of Pharmacology 2014 (DOI:10.1111/bph.12625)

Contact:
Prof. Dr. Oliver Werz
Institute of Pharmacy
Friedrich Schiller University Jena
Philosophenweg 14, 07743 Jena
Germany
Phone: ++49 3641 / 949801
Email: oliver.werz[at]uni-jena.de

Weitere Informationen:

http://www.uni-jena.de

Dr. Ute Schönfelder | idw - Informationsdienst Wissenschaft

Further reports about: DOI Pergola cytokines effective efficacy enzyme inflammatory natural reactions substances synthesis

More articles from Health and Medicine:

nachricht The genes are not to blame
20.07.2018 | Technische Universität München

nachricht Targeting headaches and tumors with nano-submarines
20.07.2018 | Universitätsmedizin der Johannes Gutenberg-Universität Mainz

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>