UK chemists have found a small molecule with the potential to overcome one of the most serious problems facing the healthcare profession today - the spread of the deadly infection MRSA. 

Methicillin-resistant Staphylococcus aureus (MRSA) is a multi-drug resistant strain of the common S. aureus bacterium that causes difficult-to-treat infections in humans. The development of new antibacterial agents to overcome this and other 'superbugs' are key targets in human medicine. With this in mind David Spring and colleagues at the University of Cambridge, UK, have used diversity-orientated synthesis to indentify a small molecule which can inhibit the enzyme that controls cell division in an epidemic strain of MRSA.

The diversity-oriented synthesis used by Spring involved making a library of 200+ structurally-diverse compounds and screening them for the required antibacterial activity against two epidemic strains of MRSA. The successful compounds were narrowed down to those with key frameworks and functional groups and were then subjected to further screening. The most potent of these was a substituted dihydropyrimidine named emmacin.

In further tests Spring showed that emmacin can selectively inhibit the key dihydrofolate reductase (DHFR) enzyme in an epidemic strain of MRSA - known as EMRSA-16. He also found that it exhibits no cytotoxic properties in mammalian systems. 

Spring suggests that emmacin may be representative of a whole new class of bacteria selective DHFR inhibitors which could be exploited in the development of critically needed new antibacterial agents. 'Bacteria are becoming resistant to DHFR inhibitors, so the more classes of compound which we can discover, the better we can tackle this problem,' he adds.

Richard Kelly