Antibacterial Antibiotics Flashcards Preview

Med Chem > Antibacterial Antibiotics > Flashcards

Flashcards in Antibacterial Antibiotics Deck (19):
1

What counts as a "good" antibiotic

1. Product of metabolism or semi-synthetic analogue of a naturally-occurring substance
2. Antagonizes the growth or survival of one or more species of microorganisms
3. Effective in low concentrations
4. Selectively toxic to organism/tissue without causing significant toxic side effects
5. Stable enough to be isolated and stored
6. Metabolism and clearance rates are amenable to dosing regimens

2

Beta-lactam antibiotics

Most common class of bacterial antibiotics
3 classes: penicillins (4-ring/5-ring systems), cephalosporins (4-ring/6-ring systems), monobactams
Selective inhibitors of bacterial cell wall biosynthesis

3

Penicillin chemical reactivity

Unstable to strongly acidic or basic conditions (breaking open penicillin ring destroys antibacterial functionality)

4

Beta-lactamase inhibitors

Mechanism-based inhibitors of beta-lactamase (enzyme that degrades penicillin)

5

Cephalosporin chemical reactivity

More resistant to beta-lactamases than penicillins
Deacylation of structure results in drug inactivation

6

Monobactams

Monocyclic class of beta-lactam antibiotics
Not heavily used

7

Aminoglycosides

Broad spectrum antibiotics used to treat both GI and systemic infections
Example: streptomycin
General structure of glycosidically-linked amino-sugars
Bind 30S ribosomal subunit to prevent initiation of amino acid polymerization

8

Aminoglycoside resistance

Though they aren't metabolized, bacteria have enzymes to inactivate them, such as amino-acetyltransferases

9

Aminoglycoside SAR

Ring 1: critical for broad-spectrum activity and primary target for inactivating enzymes
Ring 2: deoxystreptamine ring cannot be significantly changed without loss of activity
Ring 3: more tolerant to structural modifications

10

Tetracyclines

Probably most important class of broad-spectrum antibiotics
Characteristic fused ring system
Stable chelation complexes with Ca+2, Mg+2, and Fe+2 (reason why dairy products can't be consumed while taking them)

11

Tetracycline mechanism of action

Bind the 30S ribosomal subunit and prevent "docking" of amino-acyl tRNAs to A site

12

Tetracycline SAR

Analogs with fewer than 4 rings are inactive
Southern and eastern portions of system can't be significantly modified without loss of activity

13

Macrolide antibiotics

3 common characteristics:
Large lactone ring (12-16 atoms)
Ketone group
Glycosidically linked sugar
Examples: erythromycin, azithromycin

14

Macrolide antibiotic mechanism of action

Bind to bacterial 50S ribosomal subunit, preventing translocation step in protein synthesis (can't switch from A site to P site)

15

Polypeptide antibiotics

Some of the most powerful antibiotics
Renal toxicity and poor oral bioavailability
Significant structural diversity (most have a cyclic structure, D-amino acids, and other non-amino acid moieties)

16

Polypeptide antibiotic mechanism of action

Bacitracin and vancomycin inhibit bacterial cell wall synthesis
Gramicidins and polymyxins interfere with cell membrane function

17

Vancomycin

Inhibits cell wall synthesis by binding to the D-Ala-D-Ala terminus of the growing polypeptide "crosslink"
Typically considered the antibiotic last line of defense

18

Chloramphenicol

First broad-spectrum antibiotic
Inhibits bacterial protein synthesis (mechanism still not totally understood)
Contains a para-nitro group (unusual in biological compounds)

19

Novobiocin

3 parts: glycosidic sugar (noviose), coumarin ring system, benzamide side chain
Binds to DNA gyrase and can affect DNA supercoiling
Some anti-cancer properties