Podcast
Questions and Answers
What is the basic nucleus of cephalosporins?
What is the basic nucleus of cephalosporins?
- Bicyclic system
- Penicillins
- 7-ACA (correct)
- b-Lactam ring
What is the crucial component of the mechanism of cephalosporins?
What is the crucial component of the mechanism of cephalosporins?
- Acetoxy substituent
- Stereochemistry
- Carboxylic acid at position 4
- b-Lactam ring (correct)
What is the importance of the carboxylic acid at position 4?
What is the importance of the carboxylic acid at position 4?
- Important to binding (correct)
- Increases ring strain
- Helps in fermentation
- Not important to the mechanism
What is essential for high acid stability and good oral activity of cephalosporins?
What is essential for high acid stability and good oral activity of cephalosporins?
What is the limitation of generating analogues of cephalosporins?
What is the limitation of generating analogues of cephalosporins?
Why is cephaloglycin poorly absorbed orally despite having a phenylglycyl side chain?
Why is cephaloglycin poorly absorbed orally despite having a phenylglycyl side chain?
What is the role of the acetoxy group in the mechanism of cephalosporins?
What is the role of the acetoxy group in the mechanism of cephalosporins?
What happens to the 3-hydroxyl derivative under acidic conditions?
What happens to the 3-hydroxyl derivative under acidic conditions?
What is the reason for oral activity conferred by the phenylglycyl substituent?
What is the reason for oral activity conferred by the phenylglycyl substituent?
What is the importance of the bicyclic system in cephalosporins?
What is the importance of the bicyclic system in cephalosporins?
How do the in vitro antibacterial potencies of acyl derivatives of 7-ADCA compare to those of the corresponding 7-ACA analogs?
How do the in vitro antibacterial potencies of acyl derivatives of 7-ADCA compare to those of the corresponding 7-ACA analogs?
What is a characteristic of cephalosporins compared to ampicillin?
What is a characteristic of cephalosporins compared to ampicillin?
What is the significance of the 7-acylamino side chain?
What is the significance of the 7-acylamino side chain?
Why are cephalosporins considered broad-spectrum antibiotics?
Why are cephalosporins considered broad-spectrum antibiotics?
What is the purpose of the protecting group in the generation of 7-ACA?
What is the purpose of the protecting group in the generation of 7-ACA?
What is the property of the bicyclic cephem ring system that contributes to the resistance of cephalosporins to β-lactamases?
What is the property of the bicyclic cephem ring system that contributes to the resistance of cephalosporins to β-lactamases?
What is the result of hydrolysis of the secondary amide in the presence of a labile b-lactam ring?
What is the result of hydrolysis of the secondary amide in the presence of a labile b-lactam ring?
How do different cephalosporins vary in their susceptibility to hydrolysis by staphylococcal β-lactamase?
How do different cephalosporins vary in their susceptibility to hydrolysis by staphylococcal β-lactamase?
What is the main advantage of first-generation cephalosporins over penicillin G?
What is the main advantage of first-generation cephalosporins over penicillin G?
Which of the following is a characteristic of first-generation cephalosporins?
Which of the following is a characteristic of first-generation cephalosporins?
What is the main difference between first-generation and second-generation cephalosporins?
What is the main difference between first-generation and second-generation cephalosporins?
Which of the following is an example of a fourth-generation cephalosporin?
Which of the following is an example of a fourth-generation cephalosporin?
What is the structure of a first-generation cephalosporin?
What is the structure of a first-generation cephalosporin?
Which of the following is not a characteristic of first-generation cephalosporins?
Which of the following is not a characteristic of first-generation cephalosporins?
What is the main reason why Pseudonomas aeruginosa is administered by injection?
What is the main reason why Pseudonomas aeruginosa is administered by injection?
What happens to Cephalothin during metabolism?
What happens to Cephalothin during metabolism?
Why is the pyridine ring in Cephaloridine a good leaving group?
Why is the pyridine ring in Cephaloridine a good leaving group?
Why is Cefalexin administered orally?
Why is Cefalexin administered orally?
What is the effect of the methyl group at position 3 in Cefalexin?
What is the effect of the methyl group at position 3 in Cefalexin?
What is the function of the hydrophilic amino group in Cefalexin?
What is the function of the hydrophilic amino group in Cefalexin?
Which of the following is a characteristic of Cefuroxime?
Which of the following is a characteristic of Cefuroxime?
What is the main advantage of Cefuroxime over other cephalosporins?
What is the main advantage of Cefuroxime over other cephalosporins?
What is the main reason why Cefuroxime is useful?
What is the main reason why Cefuroxime is useful?
Which of the following is NOT a characteristic of First Generation Cephalosporins?
Which of the following is NOT a characteristic of First Generation Cephalosporins?
Which of the following cephalosporins is used clinically against respiratory infections?
Which of the following cephalosporins is used clinically against respiratory infections?
What is the characteristic of the aminothiazole ring in cephalosporins?
What is the characteristic of the aminothiazole ring in cephalosporins?
Which of the following is an oral cephalosporin?
Which of the following is an oral cephalosporin?
What is the activity of third-generation cephalosporins against P. aeruginosa?
What is the activity of third-generation cephalosporins against P. aeruginosa?
What is the characteristic of second-generation cephalosporins?
What is the characteristic of second-generation cephalosporins?
Which of the following is an injectable cephalosporin?
Which of the following is an injectable cephalosporin?
Study Notes
Cephalosporins
- Naturally occurring cephalosporin is cephalosporin C
- Semisynthetic modifications of the basic 7-ACA nucleus have resulted in useful antibiotics
- The 7-amino group can be acylated with different acids or undergo nucleophilic substitution or reduction of the acetoxyl group
SAR of Cephalosporins
- The beta-lactam ring is crucial to the mechanism of action
- The carboxylic acid at position 4 is important for binding
- The bicyclic system is important in increasing ring strain
- Stereochemistry is important
- The acetoxy substituent is important to the mechanism
Possible Modifications
- 7-Acylamino side chain
- 3-Acetoxymethyl side chain
- Substitution at C-7
Generation of 7-ACA
- Not possible to generate analogues by fermentation
- Not possible to generate analogues by full synthesis
- Restricted to semi-synthetic procedure
- Need to hydrolyze a relatively unreactive secondary amide in the presence of a labile beta-lactam ring
Mechanism of Action
- The acetoxy group acts as a good leaving group and aids the mechanism
- The beta-lactam ring is crucial to the mechanism
- The carboxylic acid at position 4 is important for binding
Oral Cephalosporins
- The oral activity conferred by the phenylglycyl substituent is attributed to increased acid stability of the lactam ring
- The absence of the leaving group at the 3-position is important for high acid stability and good oral activity
- The 3-hydroxyl derivatives and, especially, the corresponding lactones are considerably less active in vitro than the parent cephalosporins
Spectrum of Activity
- The cephalosporins are considered broad-spectrum antibiotics with patterns of antibacterial effectiveness comparable to that of ampicillin
- Cephalosporins are much more resistant to inactivation by beta-lactamases than ampicillin
- Ampicillin is generally more active against non-beta-lactamase-producing strains of Gram-positive and Gram-negative bacteria sensitive to both it and the cephalosporins
Beta-Lactamase Resistance
- The susceptibility of cephalosporins to various lactamases varies considerably with the source and properties of these enzymes
- Cephalosporins are significantly less sensitive than all but the beta-lactamase-resistant penicillins to hydrolysis by the enzymes from S. aureus and Bacillus subtilis
- The "penicillinase" resistance of cephalosporins appears to be a property of the bicyclic cephem ring system rather than of the acyl group
Classification of Cephalosporins
- First-generation cephalosporins: Cephalothin, Cefaloridine
- Second-generation cephalosporins: Cefuroxime, Cefaclor, Cefprozil
- Third-generation cephalosporins: Cefotaxime, Ceftazidime, Cefixime
- Fourth-generation cephalosporin: Cefepime
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Description
Learn about the structure of cephalosporins, including the basic 7-ACA nucleus and its semisynthetic modifications through acylations and nucleophilic substitution.
