Inhibitors of protein synthesis

Question 1

Why is the ribosome an important drug target?

Answer 1

because it’s responsible for the synthesis of all the protein in a cell

Question 2

Which drugs/class of drugs are inhibitors of protein synthesis?

Answer 2

Tetracyclines, fusidic acid, erythromycin and the macrolides, chloramphenicol, gentamicin and the aminoglycosides, clindamycin and the lincosamides & Linezolid and the Oxazolidinones

Question 3

What is the MoA of tetracyclines?

Answer 3

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

Question 4

Give some examples of 5 tetracyclines and their uses

Answer 4

doxycycline used in prophylaxis of malaria, lymecycline and oxytetracycline used for acne

Question 5

What is the MoA of aminoglycosides?

Answer 5

binds to 30s ribosomal subunits specifically 16S, inhibiting binding of aminoacyl tRNA and causing genetic code to be misread. Also disrupts cell wall

Question 6

Describe the structure of an aminoglycoside

Answer 6

contains several sugar rings and one or more amino acids

Question 7

Give some examples of aminoglycosides

Answer 7

gentamicin, streptomycin, kanamycin, tobramycin (which binds to 30s and 50s) and Amikacin which is derived from kanamycin

Question 8

What class of drug is Linezolid and what’s its MoA?

Answer 8

its an oxazolidinone and it binds to 50s ribosomal subunit and prevents the 30S subunit joining it, also toxic to mitochondria with 70S ribosomes

Question 9

In linezolid, the S configurations is necessary for what?

Answer 9

anti-bacterial activity

Question 10

Regarding linezolid, what does fluorination of the aryl ring do?

Answer 10

improves activity

Question 11

Describe the structure of erythromycin

Answer 11

polyketide based on propionate not acetate with alternating oxygen pattern

Question 12

What are some of the indications of macrolides?

Answer 12

TB, legionnaire’s disease, penicillin allergic patients etc

Question 13

What is the MoA of macrolides such as erythromycin?

Answer 13

inhibits protein synthesis by blocking the exit tunnel of bacterial ribosome

Question 14

What are the benefits of second generation macrolides?

Answer 14

more stable to acid, more hydrophobic

Question 15

Telithromycin is an example of what class of drugs?

Answer 15

the ketolides

Question 16

What are some mechanisms of macrolide resistance?

Answer 16

modification of ribosomal proteins and efflux pumps

Question 17

Give some example of macrolides

Answer 17

erythromycin, azithromycin, clarithromycin

Question 18

Describe the structure of chloramphenicol

Answer 18

2 chiral centres, 4 stereoisomers but only 1 is active

Question 19

Clindamycin and lincomycin are both classed as what?

Answer 19

lincosamides, contain an amide bond

Question 20

What is clindamycin used for?

Answer 20

to treat anaerobic infections and some aerobic infections like respiratory tract infections, useful for toxic shock syndrome

Question 21

Fusidic acid is classed as what?

Answer 21

Terpenoid

Question 22

What is the MoA of fusidic acid?

Answer 22

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