Med Chem of Antimycobacterial (TB) Agents

Question 1

FQ’s (Moxifloxacin)

Answer 1

• MoA: traps gyrase, prevents resolution of supercoiled DNA, disrupts DNA replication

Question 2

Ethambutol

Answer 2

• MoA: inhibits mycobac arabinosyl transferase (inhibits arabinogalactan formation in cell wall)
• synergistic w/ rifampin
• resistance due to over-expression/mutation in arabinosyl transferase

Question 3

What does mycobacterial cell wall have that G(+/-) don’t

Answer 3

• Mycolic acid and Arabinogalactan
• Makes it impermeable to many drugs

Question 4

Bedaquiline

Answer 4

• MoA: inhibits ATP synthase
• Resistance: mut in atpE

Question 5

Acid Fast Bacteria

Answer 5

• neither G(+) or G(-)
• After staining with dye, cannot be decolorized by acid wash

Question 6

Isoniazid (INH)

Answer 6

• MoA: forms adducts w/ NAD+/NADP+, inhibits enzymes that use those, inhibits mycolic acid synthesis
• Prodrug: activated by M.Tb KatG protein

Question 7

Rifampin

Answer 7

• most effective Tx
• MoA: binds to RNA polymerase deep within DNA/RNA channel

Question 8

Pretomanind

Answer 8

Nitromidazole
- prodrug; activated by M.Tb deazaflavin-dependent nitroreductase (Ddn)

Question 9

Pyrazinamide

Answer 9

• MoA: inhibits panD; inhibition of Coenzyme A synthesis
• prodrug; actived by pncA
• Resistance due to mut in pncA

Question 10

Second Line Agents

Answer 10

Less tolerated, inc AE
- Streptomycin
- Ethionamide
- Cycloserine
- Capreomycin

Question 11

What pathogen causes TB

Answer 11

Mycobacterium Tuberculosis