Researchers at the University of Georgia (Athens, Ga.; www.uga.edu) have developed a new small-molecule drug that may serve as a treatment against multidrug-resistant tuberculosis, a form of the disease that cannot be cured with conventional therapies. They describe their findings in a paper published recently in Bioorganic and Medicinal Chemistry Letters.
“There is a tremendous need for new therapies, and we think our laboratory has developed a strong candidate that disrupts fundamental steps in the bacterium's reproduction process,” said Vasu Nair, Georgia Research Alliance Eminent Scholar in Drug Discovery in the UGA College of Pharmacy and lead author of the paper.
The compound developed by Nair and his colleagues works by binding to magnesium and specific amino acids found within the bacterium, interrupting the production of RNA. “The compound...strongly inhibits the growth of the bacterium and renders it incapable of reproducing and spreading infection,” Nair explained. “More importantly, the compound shows very low levels of cytotoxicity, which means that it is not harmful to the body.”
The team also performed extensive studies to determine if the newly developed compound had an appropriately long half-life and could be cleared from the body through normal biochemical mechanisms. According to Nair, “The half-life is a little over 14 hours, and all traces of the drug are expected to be cleared through normal bodily functions.”
While Nair and his colleagues were pleased with their new compound, they were surprised to discover through preliminary experiments that it also exhibited strong anti-HIV properties, opening the door for dual therapeutic applications.
A dual-purpose drug would be a windfall for clinicians, because the risk for developing TB is between 26 and 31 times greater in people living with HIV than those without HIV infection, according to the WHO.
Journal reference
Nair, V.; Okello, M.O. et al. A novel molecule with notable activity against multi-drug resistant tuberculosis. Bioorganic & Medicinal Chemistry Letters 2015; www.sciencedirect.com/science/article/pii/S0960894X15000621