Glycylcyclines are a class of antibiotics derived from

tetracycline Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including acne, cholera, brucellosis, plague, malaria, and syphilis. Common side effects in ...

. These tetracycline analogues are specifically designed to overcome two common mechanisms of tetracycline resistance, namely resistance mediated by acquired efflux pumps and/or ribosomal protection. Presently,

tigecycline Tigecycline, sold under the brand name Tygacil, is an tetracycline antibiotic medication for a number of bacterial infections. It is a glycylcycline administered intravenously. It was developed in response to the growing rate of antibiotic resist ...

is the only glycylcycline approved for antibiotic use.

History

The development of these agents was spurred by the increasing prevalence of bacteria resistant to tetracyclines. These agents were first synthesized in the early 1990s by making modifications to the tetracyclines. By adding a bulky N,N-dimethylglycylamido

side chain In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called the "main chain" or backbone. The side chain is a hydrocarbon branching element of a molecule that is attached to a ...

to position 9 of

minocycline Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic medication used to treat a number of bacterial infections such as pneumonia. It is generally less preferred than the tetracycline doxycycline. It is also ...

, the compound became less susceptible to tetracycline resistance mediated by acquired efflux pumps and/or ribosomal protection. Further development of this initial work led to the creation of

, the first glycylcycline available for clinical use.

Approvals

Tigecycline Tigecycline, sold under the brand name Tygacil, is an tetracycline antibiotic medication for a number of bacterial infections. It is a glycylcycline administered intravenously. It was developed in response to the growing rate of antibiotic resist ...

(FDA approved May 27, 2005)

Mechanism of action

Glycylcycline antibiotics have a similar

mechanism of action In pharmacology, the term mechanism of action (MOA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targ ...

as tetracycline antibiotics. They block protein synthesis hence preventing bacterial reproduction. Both classes of antibiotics bind to the 30S

ribosomal 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 for ...

subunit to prevent the amino-acyl tRNA from binding to the A site of the ribosome. However, the glycylcyclines appear to bind more effectively than the tetracyclines.

Mechanisms of resistance

While glycylcyclines have greater efficacy against organisms with tetracycline resistance mediated by acquired efflux pumps and/or ribosomal protection, the glycylcyclines are not effective against organisms with

chromosomal efflux pump A chromosome is a long DNA molecule with part or all of the genetic material of an organism. In most chromosomes the very long thin DNA fibers are coated with packaging proteins; in eukaryotic cells the most important of these proteins are ...

s, such as ''

Pseudomonas ''Pseudomonas'' is a genus of Gram-negative, Gammaproteobacteria, belonging to the family Pseudomonadaceae and containing 191 described species. The members of the genus demonstrate a great deal of metabolic diversity and consequently are able t ...

'' and Proteae.

Side effects and contraindications

Since glycylcyclines are similar to tetracyclines, they share many of the same side effects and contraindications as tetracyclines. These side effects may include nausea/vomiting, headache,

photosensitivity Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light. In medicine, the term is principally used for abnormal reactions of the skin, and two types are distinguished, photoallergy and phototoxicit ...

, discoloration of growing teeth, and fetal damage. These antibiotics should not be given to pregnant women due to risk of fetal harm. Additionally, these drugs should not be administered during periods of tooth development because of the risk of tooth discoloration. Due to glycylcyclines' similarities with tetracyclines, hypersensitivity reactions to tetracycline antibiotics may predispose one to hypersensitivity reactions with glycylcycline antibiotics; hence, glycylcyclines should be used with caution in these patients.

References

External links

Tygacil (tigecycline IV) manufacturer website.
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{{TetracyclineAntiBiotics