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Mangosteen antibiotics against resistant bugs

23 Sep 2013

The group led by Prof Beuerman has designed new antibiotics based on natural compounds from the mangosteen

Team members in the breakthrough work (from left): Prof Beuerman, Ms Eunice Goh (graduate student from NUS’ Department of Chemistry), Mr Koh, Dr Li, Dr Liu and Dr Lakshminarayanan
The overuse of antibiotics is giving rise to resistant bugs, such that previously treatable infections have become more difficult and costly to tackle. A group of scientists from Singapore and China have synthesised a compound derived from the common mangosteen which can lead to the development of an antibiotic that kills such resistant pathogens.

Led by Professor Roger Beuerman who is with the Singapore Eye Research Institute (SERI) and Duke-NUS Graduate Medical School in Singapore, researchers from SERI, NUS, Bioinformatics Institute, Singapore General Hospital (SGH), South China University of Technology and the Chinese Academy of Sciences designed antimicrobials based on alpha-mangostin extracted from mangosteen pericarp (peel).

By conducting experiments on rabbits’ eyes which are biologically similar to humans’, the team found that the derivatives are able to destroy bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and a very special group of vancomycin-resistant bacteria. These pathogens cause some of the most deadly forms of infections.

Prof Beuerman, the Senior Scientific Director at SERI and Professor at NUS’ Departments of Ophthalmology and Biochemistry, said that existing antibiotics take eight to 20 hours to completely kill such microbes. In contrast, the most potent compound the team created is able to produce the same effect within 40 minutes.  

The results, recently published in the Journal of Medicinal Chemistry, also show that the new approach for modifying natural compounds to produce desirable properties such as improved selectivity, rapid time-kill, avoidance of antibiotic resistance and low toxicity, could be used to improve the development of new antibiotics for drug-resistant pathogens.

The study was supported by the Translational Clinical Research Program “TRIOS”, funded by Singapore’s National Research Foundation and Exploit Technologies.  Senior chemists Dr Liu Shouping and Dr Rajamani Lakshminarayanan from the NUS Department of Chemistry and SERI, together with chemical engineering post-doctoral fellow Dr Li Jianguo and chemistry graduate student Mr Koh Jun Jie, also contributed to the work.

The team has filed patents for the discovery. “We are currently talking to a number of companies and are also in the process of setting up a spinoff,” disclosed Prof Beuerman.

He said that a clinical trial is planned for this year involving some 20 patients at SGH. A second trial will recruit patients with an infection from several hospitals in Singapore, including National University Hospital and the Singapore National Eye Centre.