Dr Mauro Adamo and his research group in the RCSI Department of Pharmaceutical and Medicinal Chemistry are charting 'chemical space' in an effort to discover small molecule drug candidates.

This approach has generated compounds with demonstrated antimicrobial, anti-viral, anti-bacterial and anti-tumour activity.

"There are 1,063 drug-like molecules waiting to be discovered but choosing a starting point has always been difficult," explained Dr Mauro Adamo, a Centre for Synthesis and Chemical Biology researcher from RCSI.

The time frame for developing a new medicine can take up to 15 years and chemists have devised novel approaches before embarking on drug discovery programmes. To imagine all the chemical possibilities they use the analogy of planets in space. Chemists refer to it as chemical space and it provides a way to group molecules with similar characteristics or properties, for example, products of similar structures could all occupy similar regions in space.

"Our job as chemists is to design crafts to reach all regions of chemical space and explore the potential activity there," continued Dr Adamo. "To do this we design molecules which are versatile and could be 'moulded' to obtain different shapes. This allows us to obtain several diverse molecules through a limited number of operations."

Dr Adamo's group synthesise small molecules because they have a higher potential to become good drugs compared to many large molecules. Small molecules travel significantly better than large ones through the human body and therefore they have a higher chance of reaching their site of action. This approach has generated important classes of compounds which have demonstrated antimicrobial activity and β-lactams which were found to be useful as anti-viral, anti-bacterial and anti-tumour compounds.

"We focus on making molecules using one-pot reactions where all the reagents are added together in one reaction flask. This streamlines procedures making them practical and easy to carry out," said Dr Adamo. "In addition the starting reagents are all commercially available and inexpensive and the products we synthesise could be valuable intermediates for the generation of other diverse classes of compounds."

Synthetic procedures with long-term commercial potential must be robust and capable of being scaled up for a manufacturing environment. This innovative chemistry has many advantages in that the reagents are readily available, the yields obtained are high and the procedures straightforward to carry out.

Dr Adamo concluded: "Our overall aim is to secure funding to expand the libraries and to create a spin-off company. We hope to sell our libraries of compounds to pharmacologists so they can begin testing them for potential therapeutic value."