Inhibitors of protein synthesis Flashcards
Why is the ribosome an important drug target?
because it’s responsible for the synthesis of all the protein in a cell
Which drugs/class of drugs are inhibitors of protein synthesis?
Tetracyclines, fusidic acid, erythromycin and the macrolides, chloramphenicol, gentamicin and the aminoglycosides, clindamycin and the lincosamides & Linezolid and the Oxazolidinones
What is the MoA of tetracyclines?
they bind to 30s ribosomal subunit and prevent binding of elongation factor TU bringing with it the next amino acid in the form of aminoacyl tRNA
Give some examples of 5 tetracyclines and their uses
doxycycline used in prophylaxis of malaria, lymecycline and oxytetracycline used for acne
What is the MoA of aminoglycosides?
binds to 30s ribosomal subunits specifically 16S, inhibiting binding of aminoacyl tRNA and causing genetic code to be misread. Also disrupts cell wall
Describe the structure of an aminoglycoside
contains several sugar rings and one or more amino acids
Give some examples of aminoglycosides
gentamicin, streptomycin, kanamycin, tobramycin (which binds to 30s and 50s) and Amikacin which is derived from kanamycin
What class of drug is Linezolid and what’s its MoA?
its an oxazolidinone and it binds to 50s ribosomal subunit and prevents the 30S subunit joining it, also toxic to mitochondria with 70S ribosomes
In linezolid, the S configurations is necessary for what?
anti-bacterial activity
Regarding linezolid, what does fluorination of the aryl ring do?
improves activity
Describe the structure of erythromycin
polyketide based on propionate not acetate with alternating oxygen pattern
What are some of the indications of macrolides?
TB, legionnaire’s disease, penicillin allergic patients etc
What is the MoA of macrolides such as erythromycin?
inhibits protein synthesis by blocking the exit tunnel of bacterial ribosome
What are the benefits of second generation macrolides?
more stable to acid, more hydrophobic
Telithromycin is an example of what class of drugs?
the ketolides
What are some mechanisms of macrolide resistance?
modification of ribosomal proteins and efflux pumps
Give some example of macrolides
erythromycin, azithromycin, clarithromycin
Describe the structure of chloramphenicol
2 chiral centres, 4 stereoisomers but only 1 is active
Clindamycin and lincomycin are both classed as what?
lincosamides, contain an amide bond
What is clindamycin used for?
to treat anaerobic infections and some aerobic infections like respiratory tract infections, useful for toxic shock syndrome
Fusidic acid is classed as what?
Terpenoid
What is the MoA of fusidic acid?
binds to EFG. GTP, ternary complex binds to ribosome as normal and GTP is hydrolysed but EFG.GDP is unable to leave ribosome and protein synthesis stalled
