Two compounds exhibit antibacterial properties against tuberculosis

Researchers who tested compounds for their potential as antibiotics report they demonstrated promising activity against tuberculosis.

A team from the John Innes Centre, UK, evaluated two compounds with antibacterial properties named Redx03863 and Redx04739, which had been produced by the company Redx Pharma as antibiotic candidates, particularly against tuberculosis, which is caused by the bacterium Mycobacterium tuberculosis. The two compounds were tested in antibacterial assays. 

According to the researchers, one strategy in the search for new treatments for tuberculosis is to find compounds that exploit well-known existing targets for drugs such as the bacterial enzyme DNA gyrase. This member of the DNA topoisomerase family of enzymes is required for bacterial DNA functionality, so compounds that inhibit its activity are much sought after as antibiotic candidates.

Redx03863 and Redx04739 were also against their target, DNA gyrase, using DNA supercoiling and ATPase assays.

Using X-ray crystallography, the team elucidated the molecular details of the action of the compounds against their tuberculosis target.

They found that a very common mutation in DNA gyrase that causes bacteria to be resistant to a related group of antibiotics, the aminocoumarins, did not lead to resistance to the compounds under scrutiny here.

“We hope that companies and academic groups working to develop new antibiotics will find this study useful. It opens the way for further synthesis and investigation of compounds that interact with this target,” said Professor Tony Maxwell, one of the authors of the study. 

The results were published in the Journal of Antimicrobial Chemotherapy.