Glycylcycline
Encyclopedia
Glycylcyclines are a new class of antibiotics derived from tetracycline. 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, there is only one glycylcycline antibiotic for clinical use: tigecycline
.
to position 9 of minocycline
, 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 tigecycline
, the first glycylcycline available for clinical use.
as tetracycline antibiotics. They block protein synthesis hence preventing bacterial reproduction. Both classes of antibiotics bind to the 30S ribosomal
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.
and Proteeae.
, 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.
Efflux (microbiology)
Active efflux is a mechanism responsible for extrusion of toxic substances and antibiotics outside the cell; this is considered to be a vital part of xenobiotic metabolism...
and/or ribosomal protection. Presently, there is only one glycylcycline antibiotic for clinical use: tigecycline
Tigecycline
Tigecycline is a glycylcycline antibiotic developed by Francis Tally and marketed by Wyeth under the brand name Tygacil. It was given a U.S. Food and Drug Administration fast-track approval and was approved on June 17, 2005...
.
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 chainSide chain
In organic chemistry and biochemistry, a side chain is a chemical group that is attached to a core part of the molecule called "main chain" or backbone. The placeholder R is often used as a generic placeholder for alkyl group side chains in chemical structure diagrams. To indicate other non-carbon...
to position 9 of minocycline
Minocycline
Minocycline is a broad-spectrum tetracycline antibiotic, and has a broader spectrum than the other members of the group. It is a bacteriostatic antibiotic, classified as a long-acting type...
, 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 tigecycline
Tigecycline
Tigecycline is a glycylcycline antibiotic developed by Francis Tally and marketed by Wyeth under the brand name Tygacil. It was given a U.S. Food and Drug Administration fast-track approval and was approved on June 17, 2005...
, the first glycylcycline available for clinical use.
Mechanism of action
Glycylcycline antibiotics have a similar mechanism of actionMechanism of action
In pharmacology, the term mechanism of action refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect...
as tetracycline antibiotics. They block protein synthesis hence preventing bacterial reproduction. Both classes of antibiotics bind to the 30S ribosomal
Ribosome
A ribosome is a component of cells that assembles the twenty specific amino acid molecules to form the particular protein molecule determined by the nucleotide sequence of an RNA molecule....
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 pumps, such as PseudomonasPseudomonas
Pseudomonas is a genus of gammaproteobacteria, belonging to the family Pseudomonadaceae containing 191 validly described species.Recently, 16S rRNA sequence analysis has redefined the taxonomy of many bacterial species. As a result, the genus Pseudomonas includes strains formerly classified in the...
and Proteeae.
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, photosensitivityPhotosensitivity
Photosensitivity is the amount to which an object reacts upon receiving photons, especially visible light.- Human medicine :Sensitivity of the skin to a light source can take various forms. People with particular skin types are more sensitive to sunburn...
, 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.