Ketolides are
antibiotic
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
s belonging to the
macrolide group. Ketolides are derived from
erythromycin
Erythromycin is an antibiotic used for the treatment of a number of bacterial infections. This includes respiratory tract infections, skin infections, chlamydia infections, pelvic inflammatory disease, and syphilis. It may also be used duri ...
by substituting the
cladinose
Cladinose is a hexose deoxy sugar that in several antibiotics (such as erythromycin) is attached to the macrolide
The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy s ...
sugar with a
keto-group and attaching a cyclic
carbamate
In organic chemistry, a carbamate is a category of organic compounds with the general formula and structure , which are formally derived from carbamic acid (). The term includes organic compounds (e.g., the ester ethyl carbamate), formally o ...
group in the
lactone ring. These modifications give ketolides much broader spectrum than other macrolides. Moreover, ketolides are effective against
macrolide-resistant bacteria, due to their ability to bind at two sites at the bacterial
ribosome
Ribosomes ( ) are macromolecular machines, found within all cells, that perform biological protein synthesis (mRNA translation). Ribosomes link amino acids together in the order specified by the codons of messenger RNA (mRNA) molecules to ...
as well as having a structural modification that makes them poor substrates for efflux-pump mediated resistance.
[Bertram G. Katzung, Susan B. Masters, Anthony J. Trevor ''Basic & Clinical Pharmacology, 11e'' McGraw-Hill 2009 via "accessmedicine.com"]
Ketolides block
protein synthesis
Protein biosynthesis (or protein synthesis) is a core biological process, occurring inside Cell (biology), cells, homeostasis, balancing the loss of cellular proteins (via Proteolysis, degradation or Protein targeting, export) through the product ...
by binding to ribosomal subunits and may also inhibit the formation of newly forming ribosomes. According to a recent study comparing the action of the classic macrolides erythromycin and
azithromycin with ketolides, which are used to treat serious infections, the more powerful drugs (ketolides) were the more "leaky" in blocking the production of proteins. The researchers were surprised to discover that ketolides, which are known to be better antibiotics, allow for many more proteins to be made compared to the older, less efficient macrolides. As a result, it is now believed that allowing cells to make some proteins could be much more damaging for a microbe than not letting it make any proteins at all. The findings may point the way to better and more potent antibiotics.
The only ketolide on the market at this moment is
telithromycin, which is sold under the brand name of Ketek. Other ketolides in development include
cethromycin and
solithromycin
Solithromycin (trade name Solithera) is a ketolide antibiotic undergoing clinical development for the treatment of community-acquired pneumonia and other infections.
Solithromycin exhibits excellent ''in vitro'' activity against a broad spectru ...
.
Medical uses
Ketolides are used to treat community-acquired
bacterial pneumonia. Other
respiratory tract infections were removed as indications when it was recognized that use of
telithromycin can result in
hepatitis and
liver failure.
References
{{Protein synthesis inhibitor antibiotics