A compound from the South African tree Euclea natalensis has been found to inactivate a drug target for tuberculosis in a previously unseen way.
A team from the Department of Biological Chemistry at the John Innes Centre in Norwich, UK; the Department of Chemistry, University College London, London; and the Department of Plant Science, University of Pretoria, South Africa, investigated the compound, diospyrin, which binds to a novel site on the enzyme DNA gyrase, and inactivates it. DNA gyrase is essential for bacteria and plants but is not present in animals or humans. It is established as an effective and safe drug target for antibiotics.
‘The way that diospyrin works helps to explain why it is effective against drug-sensitive and drug-resistant strains of tuberculosis,’ said Professor Tony Maxwell from the John Innes Centre.
In traditional medicine, the antibacterial properties of Euclea natalensis, also known as the ‘toothbrush tree’ because native South Africans use twigs from the tree as toothbrushes, are used for oral health and to treat medical complaints such bronchitis, pleurisy and venereal disease.
Most antibiotics originate from natural sources, such as the soil bacteria Streptomyces. Antibiotics derived from plants are less common, but they are potentially rich sources of new medicines.
‘Extracts from plants used in traditional medicine provide a source for novel compounds that may have antibacterial properties, which may then be developed as antibiotics,’ said Professor Maxwell.
Professor Maxwell is continuing the work on diospyrin and related naphthoquinone compounds as part of the efforts of a consortium of European researchers, More Medicines For Tuberculosis (MM4TB). The collaboration between 25 labs across Europe is dedicated to the development of new drugs for TB.
The work was carried out by postdoctoral researcher Fred Collin and will be continued by South African research assistant Natassja Bush. It is published in the Journal of Biological Chemistry.