Researchers from North Carolina State University have
synthesized an analog of lipoxazolidinone A, a small molecule that is effective
against drug-resistant bacteria such as MRSA. This molecule, a new synthetic
compound inspired by a natural product, could be a useful chemical tool for
studying other Gram-positive infections and may have implications for future
drug creation.
Lipoxazolidinone A is a natural product which had been
previously isolated from bacteria living in marine sediments. It is a secondary
metabolite -- a small molecule produced by the bacteria that isn't key to its
survival but is produced for a secondary purpose, like defense. When
lipoxazolidinone A was initially isolated, researchers noted that it seemed
effective against Gram-positive bacteria, like MRSA.
NC State chemist Joshua Pierce aimed to confirm those original
findings and understand how the molecule's structure correlated to its
function; in short, he wanted to recreate the molecule to see what portions
were directly responsible for its anti-microbial properties and then
potentially improve upon that structure.
Pierce, along with current NC State graduate student Kaylib
Robinson and former students Jonathan Mills and Troy Zehnder, used novel
chemical tools to synthesize lipoxazolidinone A in the lab. They were able to
confirm that its chemical structure matched what the initial researchers had
indicated, then they worked to identify the portion of the molecule that was
responsible for the activity against Gram-positive bacteria. Their result was a
compound with improved potency, JJM-35.
They tested JJM-35 against a panel of resistant and
non-resistant bacteria. When tested against MRSA in-vitro, they found that the
synthesized molecule was up to 50 times more effective than the natural product
against several bacterial strains. Additionally, they found that the molecule
was often more effective against resistant bacterial strains than it was
against nonresistant strains.
See:
Jonathan Mills, Kaylib Robinson, Troy Zehnder, Joshua G
Pierce. Synthesis and Biological Evaluation of the Antimicrobial
Natural Product Lipoxazolidinone A. Angewandte Chemie
International Edition, 2018; DOI: 10.1002/anie.201805078Posted by Dr. Tim Sandle
