Study identifies potential new drug to treat tuberculosis

A new study published in Microbiology spectrum demonstrates that a novel semi-synthetic compound can be derived from natural compounds to produce potent activity against Mycobacterium tuberculosis, including multidrug-resistant strains. The new compound provides a promising chemical scaffold for developing powerful new anti-tuberculosis drugs.

M. tuberculosis, the pathogen responsible for tuberculosis (TB), is the leading cause of bacterial disease-related deaths worldwide. Current antibiotic regimens for the treatment of tuberculosis are outdated, require longer courses, and are at risk of developing drug resistance.

In the new study, researchers looked for new antibiotics targeting M. tuberculosis that might also be effective against drug-resistant strains. In the field of drug discovery, the world of natural compounds produced by organisms such as plants, fungi and bacteria provides a valuable starting point to begin the search for new antibiotics.

Sanguinarine, a natural compound with known antimicrobial properties, is extracted from a flowering herbaceous plant native to North America. Sanguinarine has been used in traditional and alternative medicine for animals, but its toxicity makes it unsuitable for use as a medicine in humans.

Researchers have redesigned Sanguinarine using principles of medicinal chemistry to produce a more potent antibacterial compound with reduced toxicity. In test-tube and mouse studies, the improved version of Sanguinarine, called BPD-9, was able to kill strains of M. tuberculosis resistant to all first-line antibiotics used clinically to treat tuberculosis.

Additionally, BPD-9 has been shown to be effective against non-replicating (dormant) and intracellular M. tuberculosis, two key aspects that limit the effectiveness of current anti-TB drugs. The researchers also found that BPD-9 was only active against pathogenic bacteria of the same genus as M. tuberculosis, which could spare the microbiome and other beneficial bacteria that most antibiotics harm.

“Our results show a new chemical entity that has unique properties in combating Mycobacterium tuberculosis, which could be further exploited for clinical purposes,” said the study’s corresponding author, Jim Sun, Ph.D., assistant professor in the university’s department of microbiology and immunology. University of British Columbia.

“Our finding that the new compound is effective against other members of the Mycobacterium genus could also prove useful in combating deadly lung infections caused by non-tuberculous mycobacteria, which are notoriously resistant to most antibiotics. It is also incentive to speculate that BPD-9 might kill Mycobacterium tuberculosis in a different way than existing anti-tuberculosis drugs.

The study was carried out in collaboration with the medicinal chemistry team of Weibo Yang, Ph.D. at the Shanghai Institute of Materia Medica (Chinese Academy of Sciences) and the bacterial genetics team of Marcel Behr, MD, and Andréanne Lupien, Ph.D. at McGill University.