Antibacterial compounds, active against the life-threatening superbug MRSA, have been made by UK scientists.

As MRSA (methicillin resistant Staphylococcus aureus) becomes increasingly resistant to commonly used antibiotics, the search for new types of antibiotics to combat the infection is ever more urgent.

David Spring and colleagues at the University of Cambridge, in collaboration with researchers the pharmaceutical companies AstraZeneca, Alderley Park, and Pfizer, Sandwich, used a technique called diversity-oriented synthesis to make a wide range of structurally diverse compounds, some of which have antibacterial activity against MRSA.

'Structurally diverse compound collections are essential for discovering novel pharmacologically active small molecules. Historically, natural product extracts were the source of small molecules,' said Spring. However, he added, there are significant disadvantages with this approach, such as limited availability of the natural product and difficulty in making synthetic analogues.

Spring and colleagues started their synthesis with a series of simple two-carbon molecules (based on diazoacetate). Three different reactions were carried out on each starting material, with further divergent reaction pathways being followed after that, to generate complexity.  The team ended up with 223 molecules with unique structural features.  About two percent of these molecules were found to be active against MRSA.

Mark Ladlow at the GlaxoSmithKline Cambridge Technology Centre, UK, recognised the importance of the findings.  'The number of Staphylococcus aureus infections that are resistant to the antibiotic methicillin and are contracted in hospitals is increasing,' said Ladlow. The result, he said, is an increased risk of mortality, particularly for people undergoing surgical procedures. This underlines the need for new antibiotics to treat such life-threatening infections more effectively.

The active compounds discovered by Spring and colleages are being followed up by co-workers at Addenbrooke's Hospital, Cambridge, UK, and the University of Cambridge to investigate the scope of their activity and to understand their mode of action. 

Elinor Richards