TB drug could be basis for class of broad-spectrum treatments
Chemistry professor Eric Oldfield lead the team, which determined the different ways that the drug - SQ109 - attacks the tuberculosis bacterium, how SQ109 can be tweaked to target other pathogens and how targeting the pathways reduces the probability of pathogens becoming resistant.
"Drug resistance is a major public health threat," Oldfield said. "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 multitarget 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."
Oldfield's team discovered that SQ109 blocks other proteins involved in critical functions in bacteria, fungi and parasites but not humans. It inhibits the two enzymes that make the molecule menaquinone that is involved in generating the cells' energy. SQ109 also had a third action that makes cell membranes permeable.
After creating several chemical analogs, the researchers found that SQ109 could have maximum effectiveness against certain classes of pathogens, with one analog revealed to be five times more potent against the tuberculosis bacterium than the original SQ109.