Antibacterial Agents

Question 1

Drugs that inhibit cell metabolism (1 example)

Answer 1

Sulfonamides (antimetabolites)

Question 2

Drugs that inhibit cell wall synthesis (3)

Answer 2

Penicillin Cephalosporins Vancomycin

Question 3

Drugs that affect the plasma membrane (2)

Answer 3

Polymyxins Tryothricin

Question 4

Drugs that disrupt protein synthesis (4)

Answer 4

Chloramphenicol Aminoglycosides Rifamycins Tetracyclins

Question 5

Drugs that inhibit NA transcription and replication (2)

Answer 5

Nalidixic acid Proflavine

Question 6

Sulfonamides were discovered from this compound

Answer 6

Prontosil (a prodrug converted to sulfanilamide)

Question 7

Sulfonamide SARS

Answer 7

• All groups are essential for activity
• Should be para-substituted only
• Nitrogen must only be primary or secondary
• R1 must be unsubstituted unless it’s an amide (which can be metabolized)
  *

Question 8

Long lasting sulfonamide

Answer 8

Sulfadoxine

(taken only once a week)

Question 9

Sulfonamide combination for malaria

Answer 9

Sulfadoxine + Pyrimethamine

(Fansidar)

Question 10

Sulfonamides MOA

Answer 10

• Mimic p-aminobenzoic acid (PABA) to inhibit dihydropteroate synthetase
• Block tetrahydrofolate synthesis, a cofactor for pyrimidine synthesis (for DNA)

Question 11

Trimethoprim (antimetabolite) MOA

Answer 11

Question 12

Sulfone (antimetabolite) indication

Answer 12

Leprosy

Question 13

Baterial cell wall sugars (2)

Answer 13

• N-Acetylmuramic acid (NAM)
• N-Acetylglucosamine (NAG)

Question 14

Succesfully isolated penicillin using processes such as freeze-drying and chromatography

Answer 14

Florey and Chain

Question 15

Enzyme inhibited by penicillin

Answer 15

Transpeptidase

Question 16

Penicillin action (G+ or G-)

Answer 16

• G+ since although they have a thicker cell wall, G- have a lipopolysaccharide barrier impervious to water and polar molecules
• Futhermore, most G- have b-lactamases
• G- activity if there are porins (allow hydrophilic, zwitterions to cross)
• A G+ bacteria may be immune if it has b-lactamases

Question 17

Penicillin SARS

Answer 17

• Bicyclic system: the greater the strain the greater the activity
• All are essential EXCEPT sulfur

Question 18

Adding an electron withdrawing group to the acyl side chain of the penicillin structure will render the drug:

Answer 18

Resistant to acid hydrolysis

Question 19

What is the effect of steric shields to the penicillin structure?

Answer 19

• It will give beta lactamase protection

Question 20

First effective semi-synthetic penicillin with resistance to S. aureus b-lactamase enzymes

Answer 20

• Methicillin (but it is not acid resistant)
• Whereas, Nafcillin is resistant to both b-lactamase and acid

Question 21

Examples of isoxazolyl penicillins (isoxazolyl group acts as an e- withdrawing group and stearic shield)

Answer 21

Question 22

Give the 3 classes of broad-spectrum penicillins

Answer 22

• aminopenicillins (amino group)
• caboxypenicillins (carboxylic acid group)
• ureidopenicillins (urea)

Question 23

Aminopenicillin drugs (2)

Answer 23

• Ampicillin
• Amoxicillin

Acid resistant but susceptible to b-lactamase

Question 24

Carboxypenicillin drugs (2)

Answer 24

• Carbenicillin (phenyl group)
• Ticarcillin (thiophene ring)

Question 25

Ureidopenicillin drugs (3)

Answer 25

* Azlocillin * Mezlocillin * Piperacillin

Question 26

Drug synergistic to penicillin

Answer 26

Probenecid (increase penicillin effect) * block excretion * compete with albumin binding

Question 27

Aminoacid precurors of penicillins (2)

Answer 27

* Cysteine * Valine

Question 28

Cephalosporin C SARS

Answer 28

* Six-membered ring fused to b-lactam * Presence of acetyloxy group

Question 29

Carbapenem structure

Answer 29

* Absent supfur atom in the bicyclic ring * No acyl amino side chains

Question 30

Combination of b-lactamase inhibitors + penicillins (4)

Answer 30

* Augmentin (Clavulanic acid + Amoxicillin) * Timentin (Clavulanic acid + Ticarcillin) * Unasyn (Sulbactam + Ampicillin) * Tazocin/Zosyn (Tazobactam + Piperacillin) \*broadest spectrum combinaiton

Question 31

Antibiotic from S. garyphalus which inhibits bacterial cell wall synthesis by mimicking the structure of D-Alanine and inhibiting the enzymes L-alanine racemase and D-Ala-D-Ala ligase

Answer 31

D-Cycloserine

Question 32

An antibiotic composed of 16 amino acids that is described as a tunelling molecule that act on the plasma membrane and result in the uncontrolled movement of ions across cell membrane leading to cell death

Answer 32

Gramicidin A

Question 33

An ionophore antibiotic with a cyclic structure btained from Streptomyces fermentation that acts on the plasma membrane structure by allowing the uncontrolled movement of ions across the cell membrane. This ionophore is specific for potassium ions over sodium ions.

Answer 33

Valinomycin

Question 34

A cyclic lipopeptide derived from a bacterial strain of S. roseosporus and works by disrupting multiple functions of the bacterial cell membrane

Answer 34

Daptomycin

Question 35

A bactericidal protein synthesis inhibitor that was isolated from S. griseus. This antibiotic contains a carbohydrate and basic amine groups in the structure.

Answer 35

Streptomycin

Question 36

A bacteriostatic antibiotic which inhibits protein synthesis by binding to the 30S subunit of ribosomes and preventing aminoacyl tRNA from binding. This drug was isolated from *S. aureofasciens.*

Answer 36

Chlortetracycline

Question 37

Antibiotic which has a large lactone ring, a ketone group, and a glycosidically linked amino sugar in its structure.

Answer 37

Erythromycin

Question 38

Antibiotics that inhibit the 30s subunit

Answer 38

* Aminoglycosides (gentamicin) * Tetracyclines

Question 39

Antibiotics that inhibit the 50s subunit

Answer 39

* Macrolides * Chloramphenicol * Clindamycin * Linezolid * Streptogramins (Quinupristin & Dalfopristin)

Question 40

An aminoacridine agent used topically to treat deep surface wounds. It can interact directly with bacterial DNA by intercalation

Answer 40

Proflavine

Question 41

The antibiotic isolated from S. mediterranei which inhibits G+ bacteria and works by binding noncovalently to DNA-dependent RNA polymerase and inhibiting the start of RNA synthesis.

Answer 41

Rifamycin B

Question 42

A nitroimidazole structure introduced as an anti-protozoal agent and later became an antibacterial agent. Its MOA involves the drug entering the bacterial cell wall where the nitro group is reduced and free radicals are formed and act on DNA.

Answer 42

Metronidazole

Question 43

A drug used to treat UTI where it degrades in acid conditions to give formaldehyde as the active agent.

Answer 43

Methenamine

Question 44

Chloramphenicol SAR * Which part is NOT essential? * Which part is reponsible for the toxic effect?

Answer 44

* **Dichloroacetamide** group is not essential * **Nitro group** is reponsible for the toxic effect

Question 45

Bacteriostatic agent with a 14-membered macrocyclic lactone ring

Answer 45

Erythromycin * acid instability due to ketone and alcohol groups * acid stability can be achieved by adding hydroxy groups (Clarithromycin) or by increasing the ring size to 16-members * will be LESS effective if combined with Chloramphenicol (same 50s binding site)