TB Drug May Fight Other Diseases Yet Avoid Resistance
Chemists from the University of Illinois are studying a new multi-targeted tuberculosis drug that could treat other diseases and yet avoid resistance.
SQ109 is a drug made by pharmaceutical company Sequella for the treatment of tuberculosis. Together with their collaborators, the researchers studied how the drug SQ109 attacked tuberculosis bacterium and how it can be modified to target other pathogens from yeast to malaria. The drug could become the basis for the class of a broad-spectrum of drugs that act against different fungal infections, parasites, and bacteria.
University of Illinois chemistry professor Eric Oldfield, leader of the team, said, “Drug resistance is a major public health threat. We have to make new antibiotics, and we have to find ways to get around the resistance problem. And one way to do that is with multi-target drugs. Resistance in many cases arises because there’s a specific mutation in the target protein so the drug will no longer bind. Thus, one possible route to attacking the drug resistance problem will be to devise drugs that don’t have just one target, but two or three targets.”
The team found that SQ109 blocked other proteins which play a part in critical functions in bacteria, parasites, and fungi, but not humans. The drug inhibited enzymes and possessed uncoupling action which makes the cell membrane permeable. Professor Oldfield and his team then made a dozen chemical analogs of SQ109 and tested it against certain classes of pathogens. “Given its chemical structure, we thought that some of the enzymes that we study as cancer and anti-parasitic drug targets also could be SQ109 targets. We hoped that we could make some analogs that would be more potent against tuberculosis, and maybe even against parasites.”
Findings show that SQ109 analogs could be tweaked for maximum effectiveness. One analog was discovered to be five times more effective against TB bacterium than the original drug. Other analogs also killed parasites which cause the most serious and common form of malaria.
The team’s work is supported by the National Institutes of Health and is currently focused on working with international collaborators for possible application of the drug analogs against infectious diseases such as Chagas’ disease, leishmaniasis, and sleeping sickness.