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New drugs in the pipeline for public health diseases

17.11.2005


Swedish chemists synthesizing substances for blood clots, malaria, and hepatitis C.



Chemists at Linköping University in Sweden have developed three types of molecules, protease inhibitors, that can be further developed into drugs for cardiovascular diseases, malaria, and hepatitis C.

Proteases are a group of enzymes that play a major role in the course of certain diseases. If there is a molecule present that prevents the protease from working, the disease can be cured. Such substances are called inhibitors and are already in use in many drugs today.


Per-Ola Johansson, a doctoral candidate in organic chemistry, describes in his dissertation the synthesis of such protease inhibitors, designed for potential use in combating three different diseases: cardiovascular diseases (to prevent the formation of blood clots), malaria, and chronic jaundice of the type hepatitis C.

Thrombin is a protease that plays a key role when blood coagulates. In some individuals this process is hyperactive, which can lead to the formation of blood clots. The research team at Linköping University has synthesized a series of molecules that inhibit the activity of thrombin in varying degrees. The most active of these molecules give an indication of how to go about creating the optimal thrombin inhibitor to develop a functioning drug.

Malaria, which affects some 500 million people annually, killing nearly 2 million of them, is caused by a single-cell parasite that breaks down the hemoglobin in red blood corpuscles. For tools, the parasite makes use of a number of different protease enzymes. The research team has developed a large number of molecules that inhibit the activity of two of these, plasmepsin I and II. Some of these inhibitors have proven to be extremely effective and could be optimized to become a powerful new malaria drug.

Hepatitis C is caused by the virus HCV. When it proliferates, HCV forms a chain-shaped molecule that is cut in smaller pieces by various protease enzymes, and these pieces then build up new virus particles. The team has synthesized a series of inhibitors of NS3, one of the most important of these enzymes.

This work has been carried out under the supervision of Professor Ingemar Kvarnström, Professor Bertil Samuelsson, and Åsa Rosenquist, Ph.D., and in collaboration with the pharmaceutical companies Medivir and Astra Zeneca.

The dissertation is titled Design and synthesis of inhibitors that target the serine protease thrombin, the malarial aspartyl proteases plasmepsin I and II, and the hepatitis C virus NS3 serine protease.

Åke Hjelm | alfa
Further information:
http://www.liu.se

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