The team reported that xanthones proved to be very effective at inhibiting and killing Mycobacterium tuberculosis (Mtb), the bacterium responsible for TB infection. Xanthones were also found to have a low propensity for developing drug resistance, making it a promising candidate as an anti-TB drug.
Xanthones were previously proven to be effective aginast other bacterial infections such as Staphylococcus , therefore this prompted the team to investigate its potential in tackling multi-drug resistant TB bacteria.
No need to search for new compounds"We discovered that xanthones are effective in killing off persistent strains of bacteria, a property that could result in treatment shortening therapies," says Nicholas Paton, professor in the Division of Infectious Diseases at NUS Medicine, a member of the National University Health System (NUHS).
Paton, who is also head of the Singapore Programme of Research Investigating New Approaches to Treatment of Tuberculosis (SPRINT-TB), said that the discovery of the potential of xanthones is significant as there have been no drug developments for TB in over four decades.
The usage of a proven antibacterial compound meant that there would be no need to rigorously search and test for new compounds, he adds.
TB affects an estimated 8.6 million people globally and causes approximately 1.3 million deaths annually. Asia accounts for 59% of the world's TB cases, with Singapore itself, seeing over 40 cases per 100,000 people.
Singapore's ageing population and the prevalence of diseases such as diabetes also contribute to the high incidence of TB cases. Many elderly TB patients could have also been latently infected when TB was more prevalent in the past, with the infection activating when their immune systems are more compromised.
Xanthones could potentially shorten treatment timeRecently, a staff member at a PAP Community Foundation (PCF) Sparkletots pre-school in Clementi was found with active tuberculosis and triggered a mass screening of staff and children who was in close contact with infected staff. All have been screened, with 45 testing negative and 21 pending doctor's evaluation. All 66 do not suffer from active TB.
The fight against TB has been a global struggle, with WHO focusing as much research and prevention programmes on the disease. Common strains of TB have begun to develop multi-drug resistance, and with a small pool of drugs that are effective against the disease, this raises concern. In addition, there is a low number of potential new chemical entities in the TB drug pipeline currently.
"The average TB patient currently expects to undergo six to 24 months of tedious treatment," says 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.
While laboratory and preclinical testing on xanthones will take at least several more years but Dick says that this offers a realistic avenue towards developing new and more effective drugs for TB with potentially shortened treatment tiems as well.
SPRINT-TB is also working with BSL-3 to quicken the investigation into xanthones and other potential TB treatment methods. MIMS
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