A drug candidate going through clinical trials to cure tuberculosis could be the foundation for a class of broad-spectrum medicines that act against numerous bacteria, fungal infections and parasites, yet evade resistance, with respect to a research published by University of Illinois chemists and collaborators.
Lead author chemistry professor Eric Oldfield and his team identified the various ways the drug SQ109 strikes the tuberculosis bacterium, how the drug can be modified to target other pathogens from yeast to malaria — and how aiming for multiple pathways decreases the possibility of pathogens getting resistant. SQ109 is designed by Sequella Inc, a US based pharmaceutical organization.
Led author Oldfield said “Drug resistance is a main public health risk” to over come this We should develop new antibiotics, and we must identify approaches to get around the resistance issue. And one way to do that is with multitarget medicines. Resistance in lot of cases occurs due to the fact there’s a particular mutation in the target protein so the drug will no longer bind. Thus, one feasible route to fighting the drug resistance issue will be to develop drugs that don’t have simply one target, but two or three targets.”
Author read published reports regarding SQ109 and noticed that the drug would probably be multifunctional due to the fact it had chemical functions identical to those identified in other systems he had researched. The initial developers had recognized one key action against tuberculosis, it is preventing a protein engaged in developing the cell wall of the bacterium, but conceded that the drug could have other activities within the cell also since it was identified to destroy other bacteria and fungi that lacked the target protein. Author thought he could determine those activities and probably enhance upon SQ109.
“I was studying Science magazine one day and noticed this molecule, SQ109, and I believed, that seems a bit like molecules we’ve been examining that have several targets,” Oldfield stated. “Given its chemical structure, we believed that some of the enzymes that we research as cancer and antiparasitic drug targets also could be SQ109 targets. We expected that we could develop some analogs that would be more effective against tuberculosis, and perhaps even against parasites.”
By researching SQ109 for themselves, Oldfield’s team identified that SQ109 does certainly block other proteins engaged in crucial functions in fungi, parasites and bacteria but not humans. They identified it prevents two enzymes that make the molecule menaquinone, which is engaged in producing the cell’s energy. Then they identified that SQ109 had a 3rd action, known as uncoupling, which makes the cell membrane permeable effectively transforming the membrane from a wall to a screen door.
Now, the scientists are performing with global collaborators to implement SQ109 analogs towards other infectious diseases rampant in the tropical world, like as Chagas’ disease, sleeping sickness and leishmaniasis.
Oldfield considers that multiple-target medicines, like SQ109 and its analogs carry the key to antibiotic advancement in the age of drug resistance and the increase of so-called “superbugs.” Proof facilitates that evaluation: So far, in experiments with tuberculosis, no instances of SQ109 resistance have been claimed.