UAntwerp scientists create promising method for the development of new drugs

Molecules are at the foundation of every effective medicine. Scientists regularly predict promising new building blocks for these molecules, but converting them for practical use is a major challenge and that is where things often go wrong. Researchers at UAntwerp came up with a new method using catalysis, which can boost the development of new medicines.

Medicines are essential to live a long, high-quality life. They mostly consist of organic molecules made of carbon, hydrogen, nitrogen and oxygen atoms. Scientists regularly track down promising molecules using computer models, but in practice conversion to an effective drug is unfortunately very difficult and sometimes impossible. There is a big limit to what is accessible in so-called 'chemical space', consisting of all possible organic molecules.

The third dimension

‘It is comparable to space research: space is infinitely large and we only know about a small part of it. However, we strongly suspect that a planet with Earth-like life does exist somewhere in space. We just have not discovered it yet’, says Professor Bert Maes, Collen-Francqui research professor at UAntwerp’s Department of Chemistry and spokesperson for the CASCH consortium of research excellence.

The medicines we know so far are mostly 'flat’, like a pancake. The realisation that the third dimension is essential to improve efficacy and efficiency (selectivity, solubility in water and lipids, stability) has only come about recently, posing additional synthesis challenges. Drug development using 3D techniques is severely hampered by what is chemically possible.

Synthesis chemistry

Maes: ‘It must be done in a limited number of steps in order to synthesise large numbers of organic molecules based on the same building block, the so-called libraries. This can be compared to a key (= the building block) where the teeth (= decoration) determine which lock you can open. You need a very large number of keys with different decorations to find just the right one to open your lock (= what you are working on for treatment of the disease). If the key-making is inefficient, you will never find the right one, because you just cannot make enough.’

Innovations from organic synthesis chemistry are therefore crucial and a cornerstone in modern drug development. Synthesis chemistry involves the development of advanced methods that can selectively create and break new chemical bonds. At the University of Antwerp’s Organic Synthesis Department, research is being done to develop efficient ways of creating complex molecules, in which different bonds are very selectively formed one after the other in just one step: 'cooking' for the advanced.

Specific bindings

The Antwerp researchers discovered a new method based on catalysis in the laboratory. Catalysts are not consumed and can therefore be added in very small quantities to make and break specific bonds. Catalysis is crucial for the chemical industry today, where 90% of commercially produced chemicals are prepared using a catalyst. Maes: ‘By combining two metal catalysts (palladium and copper), complex nitrogenous molecules (= decorated building blocks) can be obtained in one step from simple and readily available raw materials.’

The industry has shown interest in this method. Maes: ‘We have already been contacted by companies with specific questions.’

The research project was made possible thanks to the Research Foundation Flanders (FWO) and its Walloon counterpart FNRS, and is part of a collaboration with ULB. A paper with the research results will appear in Angewandte Chemie International Edition, one of the most prestigious journals in the field of chemistry.