New compounds may lead to next generation antibiotics
Researchers at North Carolina State State University synthesized a simulation of lipoxazolidinone A, a small molecule that is effective against drug-resistant bacteria such as MRSA.This molecule, a new synthetic compound inspired by natural products, may be a useful chemical tool for studying other gram-positive infections and may have an impact on future drug creation. Lipoxazolidinone is a natural product that was previously isolated from bacteria living in marine sediments. It is a secondary metabolite-a small molecule produced by bacteria that is not the key to survival, but arises from a second purpose, such as defense. When Lipoxazolidinone was initially isolated, the researchers pointed out that it appeared to be effective against Gram-positive bacteria, such as MRSA.
NC State Chemist The purpose of Joshua is to confirm these original discoveries and understand how the structure of the molecule is related to its function; In short, he wants to recreate the molecule to see which parts are directly responsible for its antimicrobial properties and then possibly improve on this structure. Pierce, along with the current NC national graduate Kaylib Robinson and former student Jonathan Mills and Troy Zeng, uses new chemical tools to synthesize lipoxazolidinone A in the lab. They were able to confirm that its chemical structure was consistent with what the original researchers had pointed out, and then they tried to find parts of the molecule responsible for the Gram-positive bacteria.Their result is an enhanced potency of the compound, JJM-35.
They conducted JJM-35 tests on a group of drug-resistant and antibiotic-resistant bacteria. In vitro detection of MRSA, they found that the synthesis of molecules than natural products for several bacterial strains of the efficacy of 50 times times higher. In addition, they found that molecules tend to resist bacterial strains more effectively than nonresistant strains.
"An exciting additional aspect of this work is that we have found that these molecules may inhibit the direct or indirect function of multiple biosynthetic pathways," Pierce said.
"This means that bacteria may struggle to develop resistance to potential drugs developed from these molecules." Although more work is needed, Pierce hopes JJM-35 and similar compounds can be used as tools to study other gram-positive bacteria and provide a platform to develop a new class of anti-infective drugs.
"At this point we have a chemical scaffold--a starting part of a puzzle." We know this article is valid, so now all efforts are focused on assessing the nature of these molecules and their efficacy in vivo, Pierce said.
"Our hope is that we can build on this scaffold to create drugs, for MRSA and other antibiotic-resistant bacteria, when there is an urgent need for antibiotic development, and also to increase the range of activities." The study is published in the Journal of Applied Chemistry. The work was funded by the National Institutes of Health (R01GM110154) and the NC National Finance Minister's Innovation fund, as well as the Institute of Comparative Medicine in NC State.
