Inhibitors of Protein synthesis

Protein synthesis - Recap

Formation of the Initiation Complex

Joining of 50S Ribosomal Subunit

Protein Elongation

Termination of Translation

Aminoglycoside

Aminoglycosides
• Streptomycin – 1944
• Actinomycetes – Streptomyces griseus
• Bactericidal antibiotics
• Interfere with protein synthesis
• Used to treat aerobic Gram –ve bacteria
• Resemble each other in MOA, pharmacokinetic
therapeutic and toxic properties
• Relatively low margin of safety
• Exhibit ototoxicity and nephrotoxicity

Aminoglycosides
• Systemic
– Streptomycin
– Gentamicin
– Kanamycin
– Amikacin
– Sisomicin
– Tobramycin
– Netilimicin
• Topical
– Neomycin
– Framycetin

Mechanism of action
• Initially they penetrate
bacterial cell wall, to reach
periplasmic space through
porin channels (passive
diffusion)
• Further transport across
cytoplasmic membrane takes
place by active transport by
proton pump; an oxygen-
dependent process

Mechanism of Action
•
•
• Bind 30S ribosomal
subunits and interfere
the initiation complex
Induce misreading of
genetic code on mRNA
Breakup of polysomes
into monosomes

Chloramphenicol
• An antibiotic produced by Streptomyces
venezuelae, an organism first isolated in
1947 from a soil sample collected in
Venezuela.

Mechanism of Action
•
•
Chloramphenicol inhibits protein synthesis in bacteria and,
to a lesser extent, in eukaryotic cells. The drug readily
penetrates bacterial cells, probably by facilitated diffusion.
Chloramphenicol acts primarily by binding reversibly to the
50 S ribosomal subunit. Although binding of tRNA at the
codon recognition site on the 30 S ribosomal subunit is thus
undisturbed, the drug appears to prevent the binding of the
amino-acid-containing end of the aminoacyl tRNA to the
acceptor site on the 50 S ribosomal subunit. The interaction
between peptidyltransferase and its amino acid substrate
cannot occur, and peptide bond formation is inhibited

• Chloramphenicol also can inhibit mitochondrial protein
synthesis in mammalian cells, perhaps because
mitochondrial ribosomes resemble bacterial ribosomes
(both are 70 S) more than they do the 80 S cytoplasmic
ribosomes of mammalian cells.

Tetracycline

INTRODUCTION
•Tetracyclines is a group of antibotic that
include tetracycline.
•Tetracyclines are obtained by fermentation
from Streptomyces spp. Or by chemical
transformation of natural products.
• They are derivatives of an octahydro-
naphthacene,a hydrocarbon system that
comprises four annulated six member rings.
•
•
•

Mechanism of Action
• Tetracyclines are specific inhibitors of
bacterial protein synthesis. They bind to the
30S ribosomal subunit and thereby prevent
the binding of aminoacyl tRNA to the mRNA
ribosome complex.
• Tetracyclines also inhibit protein synthesis in the
host ,but are less likely to reach the concentration
required because eukaryotic cells do not have a
tetracycline uptake mechanism.

Macrolides

• Inhibits protein synthesis by reversibly binding to
the 50S ribosomal subunit
– Suppression of RNA-dependent protein synthesis
by inhibition of translocation of mRNA
• Typically bacteriostatic activity
• Bactericidal at high concentrations against very
susceptible organisms