A study by researchers from the National University of Singapore’s Yong Loo Lin School of Medicine (NUS Medicine) has uncovered that xanthones in mangosteens could provide a suitable new drug in the fight against tuberculosis. The study published in the European Journal of Medicinal Chemistry found that xanthones were very effective at inhibiting and killing Mycobacterium tuberculosis (Mtb), the bacterium responsible for causing TB.
Carried out under the Singapore Programme of Research Investigating New Approaches to Treatment of Tuberculosis (SPRINT-TB), a multi-party programme based in Singapore, the study also demonstrated that xanthones had a low propensity for developing drug resistance, making it a promising candidate in developing anti-TB drugs. In this study, the xanthones exhibited potent MIC, rapid time-kill and no cross-resistance with the current anti-TB drugs.
TB is an infectious disease affecting an estimated 8.6 million people globally and is responsible for some 1.3 million deaths annually. Developed nations in Europe and North America have reduced TB rates of between 5 and 10 per 100,000 people each year compared to Singapore, which sees over 40 cases per 100,000 people. Asia accounts for 59% of the world’s TB cases. A rapidly ageing population and the prevalence of diseases such as diabetes also contribute to the high incidence of TB cases, as compromised immune systems make the aged more susceptible to infections. Many elderly TB patients could also have been latently infected when the disease was far more prevalent in the past, with the infection reactivating as they age.
Earlier studies in Singapore using mangosteen fruit extracts found that xanthones were effective against bacterial infections such as Staphylococcus. This prompted the researchers to investigate the potential for this class of compounds in tackling multi-drug resistant TB bacteria.
“We discovered that xanthones are effective in killing off persistent strains of bacteria, a property that could result in treatment shortening therapies,” said head of SPRINT-TB Professor Nicholas Paton, Division of Infectious Diseases, NUS Medicine, a member of the National University Health System (NUHS). “The discovery of this new potential TB drug candidate is significant; aside from two new drugs approved in recent years for multidrug-resistant TB, the disease had not seen new drug developments in over 40 years. Using a proven antibacterial compound like xanthones means we do not have to re-invent the wheel by searching for and testing totally new compounds.”
The fight against TB is an uphill struggle. Common strains of TB have developed multi-drug resistance, rendering existing drugs ineffective against the disease. There is also a worryingly low number of potential new chemical entities in the TB drug pipeline at present. With patients facing a daunting treatment regimen lasting six months or more, xanthones could prove an attractive option in tackling multi-drug resistant TB.
“The average TB patient currently expects to undergo six to 24 months of tedious treatment. Xanthones offer a realistic avenue towards developing new and more effective drugs for TB with potentially shortened treatment times as well. All these factors can help in reducing the disease burden faced by Singapore’s ageing population, as well as treatment costs incurred by patients and their families” said Associate Professor Thomas Dick, the study’s principal investigator and head of the Antibacterial Drug Discovery Laboratory and Director of the Biosafety-level 3 (BSL-3) Core Facility at NUS Medicine.