Cephalosporins are a major class of β-lactam antibiotics characterized by a β-lactam ring fused to a dihydrothiazine ring, forming the cephem nucleus (7-ACA core). Their structure–activity relationship (SAR) is driven by substituents at C7 (acylamino side chain) and C3 (side chain/leaving group), which modulate PBP affinity, spectrum, β-lactamase stability and pharmacokinetics. Chemical features such as methoxyimino, 7-α-methoxy and aminothiazole moieties determine stability and Gram-negative coverage across generations. Understanding cephalosporin chemistry, SAR, synthesis and generation-wise spectrum is essential for B.Pharm students preparing for exams and clinical application. These MCQs cover core concepts, mechanism of action, spectral differences, structural modifications and clinical relevance. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is the core cephem structure of cephalosporins?
- A β-lactam ring fused to a dihydrothiazine ring (7-ACA core)
- A β-lactam ring fused to a thiazolidine ring
- A macrolide lactone ring
- A tetracyclic steroid nucleus
Correct Answer: A β-lactam ring fused to a dihydrothiazine ring (7-ACA core)
Q2. What does 7‑ACA stand for in cephalosporin chemistry?
- 7‑acetyl cephalosporin A
- 7‑aminocephalosporanic acid
- 7‑alkyl cephalosporin analogue
- 7‑active cephamycin acid
Correct Answer: 7‑aminocephalosporanic acid
Q3. Which positions on the cephem nucleus are most important for SAR modifications?
- C1 and C2 positions
- C3 and C7 positions on the cephem nucleus
- N1 and C4 positions
- C5 and C6 positions
Correct Answer: C3 and C7 positions on the cephem nucleus
Q4. The C7 acylamino side chain primarily influences which property?
- Renal clearance only
- Antibacterial activity and PBP binding
- Oral taste
- Color of the drug solution
Correct Answer: Antibacterial activity and PBP binding
Q5. Modifications at the C3 position commonly affect which of the following?
- Only the taste of the oral formulation
- Pharmacokinetics, β-lactamase stability and spectrum
- Formation of a macrolide ring
- Conversion to penicillin nucleus
Correct Answer: Pharmacokinetics, β-lactamase stability and spectrum
Q6. Which substituent is characteristic of cephamycins and confers increased β-lactamase resistance?
- Methoxyimino group at C7
- 7‑α‑methoxy group
- Aminoglycoside side chain
- Macrolide linkage at C3
Correct Answer: 7‑α‑methoxy group
Q7. What is the primary mechanism of action of cephalosporins?
- Inhibition of DNA gyrase
- Disruption of 30S ribosomal subunit
- Inhibition of penicillin‑binding proteins, preventing peptidoglycan crosslinking
- Blocking folate synthesis
Correct Answer: Inhibition of penicillin‑binding proteins, preventing peptidoglycan crosslinking
Q8. Which cephalosporin generation typically offers broad Gram-negative coverage and improved β‑lactamase stability?
- First generation
- Second generation
- Third generation
- Fourth generation
Correct Answer: Fourth generation
Q9. Which cephalosporin is a fifth-generation agent with activity against MRSA?
- Cefazolin
- Ceftaroline
- Cefuroxime
- Cefalexin
Correct Answer: Ceftaroline
Q10. Which of the following is a first‑generation cephalosporin commonly taught in B.Pharm courses?
- Cefalexin
- Cefotaxime
- Cefepime
- Ceftazidime
Correct Answer: Cefalexin
Q11. How is 7‑ACA typically obtained for semisynthetic cephalosporin synthesis?
- Total chemical synthesis from benzene
- Enzymatic or chemical removal of the side chain from natural cephalosporin C
- Extraction from penicillin G
- Synthesis from erythromycin scaffold
Correct Answer: Enzymatic or chemical removal of the side chain from natural cephalosporin C
Q12. In SAR terms, what is the role of a good leaving group at C3?
- It decreases antibacterial activity by stabilizing the molecule
- It enhances activity in some cephalosporins by facilitating interactions and cell entry
- It converts the drug to a macrolide
- It prevents renal excretion completely
Correct Answer: It enhances activity in some cephalosporins by facilitating interactions and cell entry
Q13. Which prodrug strategy is used to improve oral bioavailability of some cephalosporins?
- Axetil ester prodrug (e.g., cefuroxime axetil)
- Intravenous lipid emulsion
- Direct inhalation powder
- Sublingual nitrate salt
Correct Answer: Axetil ester prodrug (e.g., cefuroxime axetil)
Q14. Which side chain is associated with hypoprothrombinemia and a disulfiram‑like reaction?
- Methylthiazole group
- N‑methylthiotetrazole (NMTT/MTT) side chain
- Aminothiazole ring
- Methoxyimino moiety
Correct Answer: N‑methylthiotetrazole (NMTT/MTT) side chain
Q15. The methoxyimino group at C7 primarily provides which SAR advantage?
- Enhanced binding to PBP2a only
- Improved β‑lactamase stability
- Increased oral bitterness
- Reduced molecular weight
Correct Answer: Improved β‑lactamase stability
Q16. What is the name of the six‑membered sulfur‑containing ring fused to the β‑lactam in cephalosporins?
- Thiazolidine ring
- Dihydrothiazine ring (cephem nucleus)
- Pyridine ring
- Imidazole ring
Correct Answer: Dihydrothiazine ring (cephem nucleus)
Q17. Which generation is most commonly used for empirical treatment of bacterial meningitis because of good CSF penetration?
- First generation
- Second generation
- Third generation (e.g., cefotaxime, ceftriaxone)
- Fifth generation
Correct Answer: Third generation (e.g., cefotaxime, ceftriaxone)
Q18. Increasing bulk or polarity of the C7 acyl side chain generally affects PBP affinity how?
- Decreases PBP affinity universally
- Can increase affinity by better mimicking the D‑Ala‑D‑Ala substrate
- Eliminates β‑lactam activity
- Makes the molecule fluorescent
Correct Answer: Can increase affinity by better mimicking the D‑Ala‑D‑Ala substrate
Q19. Cephamycins differ from cephalosporins mainly because they contain which group?
- 7‑α‑methoxy group
- A second β‑lactam ring
- Macrolide side chain
- Quinolone nucleus
Correct Answer: 7‑α‑methoxy group
Q20. How does a methoxyimino (oxime) substituent confer β‑lactamase resistance?
- By acting as an enzyme inhibitor in the cytoplasm
- By sterically hindering access of β‑lactamases to the β‑lactam bond
- By chelating metal ions in the cell wall
- By promoting rapid renal clearance
Correct Answer: By sterically hindering access of β‑lactamases to the β‑lactam bond
Q21. Which bacterial resistance mechanism commonly hydrolyzes third‑generation cephalosporins?
- Efflux pump overexpression only
- Extended‑spectrum β‑lactamases (ESBLs)
- Alteration of ribosomal RNA
- Reduced folate synthesis
Correct Answer: Extended‑spectrum β‑lactamases (ESBLs)
Q22. Which cephalosporin has a long plasma half‑life allowing once‑daily dosing and high protein binding?
- Cefalexin
- Ceftriaxone
- Ceftazidime
- Cefazolin
Correct Answer: Ceftriaxone
Q23. Presence of which ring at C7 is associated with enhanced Gram‑negative activity including Pseudomonas coverage?
- Phenyl ring without heteroatoms
- Aminothiazole ring
- Furanose moiety
- Steroid nucleus
Correct Answer: Aminothiazole ring
Q24. What is a key structural difference between cephalosporins and penicillins?
- Cephalosporins lack a β‑lactam ring while penicillins have one
- Cephalosporins have a six‑membered dihydrothiazine ring; penicillins have a five‑membered thiazolidine ring
- Penicillins contain an aminoglycoside moiety
- Cephalosporins contain a macrolactone ring
Correct Answer: Cephalosporins have a six‑membered dihydrothiazine ring; penicillins have a five‑membered thiazolidine ring
Q25. Altering side chains to make them dissimilar to penicillins mainly affects which clinical concern?
- Reduces allergic cross‑reactivity with penicillins
- Causes immediate renal toxicity
- Makes the drug inactive against Gram‑positive cocci
- Increases production cost only
Correct Answer: Reduces allergic cross‑reactivity with penicillins
Q26. Which cephalosporin modification is commonly used to create an orally absorbable prodrug?
- Conversion to an axetil ester
- Introduction of an NMTT side chain
- Removal of the β‑lactam ring
- Attachment of a macrolide moiety
Correct Answer: Conversion to an axetil ester
Q27. Which laboratory reagent is commonly used to detect β‑lactamase activity visually?
- Gram stain
- Nitrocefin
- Mannitol salt agar
- Citrate buffer
Correct Answer: Nitrocefin
Q28. Which structural feature allows some cephalosporins to bind altered PBPs like PBP2a in MRSA?
- Small nonpolar C3 groups only
- Specific C7 side chains that increase PBP affinity (e.g., ceftaroline)
- Loss of the β‑lactam ring
- Presence of a glycopeptide tail
Correct Answer: Specific C7 side chains that increase PBP affinity (e.g., ceftaroline)
Q29. Which generation includes agents like cefotaxime and ceftriaxone that show enhanced Gram‑negative coverage compared to earlier generations?
- First generation
- Second generation
- Third generation
- Fifth generation
Correct Answer: Third generation
Q30. The oxime (methoxyimino) and aminothiazole substituents generally contribute to which combined SAR effect?
- Improved Gram‑positive activity only
- Improved Gram‑negative penetration and β‑lactamase stability
- Conversion into aminoglycoside antibiotics
- Enhanced gastrointestinal toxicity without antibacterial benefit
Correct Answer: Improved Gram‑negative penetration and β‑lactamase stability
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