ID Medchem Dr. Brown Flashcards
Natural VS Synthetic penicillins
-generated from organisms that kill other organisms
a -natural product that is chemically modified
What are the functions of the side chains of penicillins?
-the difference in drug stability
-stability against enzymes
-Protein binding characteristics
-antimicrobial coverage
What makes penicillins vulnerable?
The amid in the ß-lactam ring
-vulnerable to hydrolysis
-aqueous environment
-enzymes: ß-lactamase
How does ß-lactamase affect the stability of penicillins?
-Serine residue initiates a nucleophilic attack on the carbonyl of the ß-lactam ring -> breaking up the ring
How can ß-lactams rings be protected by hydrolysis?
-Steric protection: large side chain
-Electronic protection: EWGs like fused rings or halogens
-ß-lactamase inhibitor
How do EWGs protect ß-lactam rings from hydrolysis?
Because they withdraw electrons, thereby making it less reactive -> Deactivate the ring
What are the differences between Penicillins and Cephalosporins?
-6 membered ring: DIHYDROTHIAZINE RING
-2 substitutes
Which of the positions in the Cephalosporin structure would be modified to provide protection to the ß-lactam ring?
Position 3
-but it also affects antimicrobial coverage
Position for synthetic modification
Position 7
-affects binding of ß-lactamase (protect)
-also affects antimicrobial coverage
Why is the Carboxylic group on Position 1 useful for a drug formulation?
It can be used to generate a prodrug by adding an ester that can be hydrolyzed to activate the drug
How can the Dihydrothiazine ring be modified?
The S (sulfur atom) can be exchanged
-O (oxacepham)
-C (carbacepham)
What is the difference between cepham and cephem rings?
Cepham = single bond in the Dihydrothiazine ring
Cephem = double bonded
