Myxopyronins (Myx) are a group of alpha-
pyrone
Pyrones or pyranones are a class of heterocyclic chemical compounds. They contain an unsaturated six-membered ring, which has one oxygen atom and a carbonyl functional group. There are two isomers, denoted as 2-pyrone and 4-pyrone. The 2-pyrone ...
antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy ...
s, which are inhibitors of bacterial
RNA polymerase
In molecular biology, RNA polymerase (abbreviated RNAP or RNApol), or more specifically DNA-directed/dependent RNA polymerase (DdRP), is an enzyme that catalyzes the chemical reactions that synthesize RNA from a DNA template.
Using the e ...
(RNAP).
They target switch 1 and switch 2 of the RNAP "switch region".
Rifamycin
The rifamycins are a group of antibiotics that are synthesized either naturally by the bacterium '' Amycolatopsis rifamycinica'' or artificially. They are a subclass of the larger family of ansamycins. Rifamycins are particularly effective aga ...
s and
fidaxomicin
Fidaxomicin, sold under the brand name Dificid (by Merck) among others, is the first member of a class of narrow spectrum macrocyclic antibiotic drugs called tiacumicins. It is a fermentation product obtained from the actinomycete '' Dactylosp ...
also target RNAP, but target different sites in RNAP. Myxopyronins do not have
cross-resistance
Cross-resistance is when something develops resistance to several substances that have a similar mechanism of action. For example, if a certain type of bacteria develops antimicrobial resistance to one antibiotic, that bacteria will also have res ...
with any other drugs so myxopyronins may be useful to address the growing problem of
drug resistance
Drug resistance is the reduction in effectiveness of a medication such as an antimicrobial or an antineoplastic in treating a disease or condition. The term is used in the context of resistance that pathogens or cancers have "acquired", that is ...
in tuberculosis. They also may be useful in treatment of
methicillin-resistant ''Staphylococcus aureus'' (MRSA). They are in
pre-clinical development
In drug development, preclinical development (also termed preclinical studies or nonclinical studies) is a stage of research that begins before clinical trials (testing in humans) and during which important feasibility, iterative testing and dr ...
and has not yet started
clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...
s.
Myxopyronin was first isolated in 1983 from a soil bacterium by Werner Kohl and Herbert Irschik at the Helmholtz Centre for Infection Research (former GBF).
[ A total synthesis of myxopyronin was first reported in 1998 by James S. Panek and co-workers.
The target, the mechanism of action, and the structure of the complex of RNAP with myxopyronin were first reported in 2008 by Richard H. Ebright and co-workers. Synthetic analogs of the natural myxopyronins have been synthesized at Anadys Pharmaceuticals and at Rutgers University.
Terence I. Moy and co-workers at Cubist Pharmaceuticals have stated that, based on high resistance rate and high serum protein binding (comparable to rifamycins and lipiarmycin), the unmodified natural product myxopyronin B is not a viable starting point for antibiotic development.]
References
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Antibiotics
4-Pyrones