Macrolide & β-lactam antibiotics: chemistry and modifications MCQs With Answer

Macrolide & β-lactam antibiotics: chemistry and modifications MCQs With Answer is a focused quiz collection designed for M.Pharm students preparing for advanced courses and exams in natural product chemistry. These questions emphasize core chemical structures, biosynthetic origins, structure–activity relationships (SAR), semisynthetic modifications, and mechanisms of resistance. The set integrates synthetic strategies used to improve stability, spectrum, and oral bioavailability, and contrasts chemical features of macrolides (lactone rings, deoxy sugars) with β-lactams (penams, cephems, carbapenems). Each MCQ includes concise options and direct answers to help reinforce understanding and retention of critical concepts relevant to formulation, medicinal chemistry, and antimicrobial drug design.

Q1. Which functional group in macrolide antibiotics primarily influences their binding to the bacterial 50S ribosomal subunit?

• The β-lactone ring
• The desosamine sugar at C5/C3
• The 3-phenylpropionyl side chain
• The dihydrothiazine ring

Correct Answer: The desosamine sugar at C5/C3

Q2. In β-lactam antibiotics, which structural feature is most directly responsible for acylation of penicillin-binding proteins (PBPs)?

• The lactone carbonyl of macrolides
• The strained four-membered β-lactam carbonyl
• The 14-membered macrolactone ring
• The carbapenem fused pyrroline ring

Correct Answer: The strained four-membered β-lactam carbonyl

Q3. Which chemical modification is central to creating ketolides from erythromycin derivatives?

• Oxidation of the cladinose sugar to a ketone at C3
• Reduction of the lactone ring to a lactam
• Introduction of a β-lactam moiety at C6
• Attachment of a carbapenem side chain

Correct Answer: Oxidation of the cladinose sugar to a ketone at C3

Q4. Which semisynthetic modification enhances oral acid stability of erythromycin to produce clarithromycin?

• Methylation of the 6-OH to form 6-O-methyl
• Removal of the desosamine sugar
• Hydrogenation of the lactone double bond
• Introduction of an amino group at C11

Correct Answer: Methylation of the 6-OH to form 6-O-methyl

Q5. Which structural change differentiates cephalosporins from penicillins?

• Presence of a 14-membered lactone ring
• Replacement of thiazolidine by dihydrothiazine fused to the β-lactam
• Incorporation of desosamine sugar
• Fused oxazolidinone ring at C3

Correct Answer: Replacement of thiazolidine by dihydrothiazine fused to the β-lactam

Q6. Which modification in macrolides was introduced to overcome macrolide efflux mediated by Msr(A) proteins?

• Removal of desosamine sugar
• Introduction of bulky alkyl-aryl side chains at the lactone periphery (e.g., telithromycin)
• Insertion of a β-lactam ring into the macrocycle
• Fluorination of the lactone carbonyl

Correct Answer: Introduction of bulky alkyl-aryl side chains at the lactone periphery (e.g., telithromycin)

Q7. Which reagent or strategy is typically used to open the β-lactam ring during hydrolysis by β-lactamases?

• Nucleophilic attack by an active-site serine hydroxyl
• Oxidative cleavage by cytochrome P450
• Photochemical ring opening via UV light
• Pericyclic rearrangement to an enamine

Correct Answer: Nucleophilic attack by an active-site serine hydroxyl

Q8. Which substituent on the 7-aminocephalosporanic acid (7-ACA) nucleus primarily influences Gram-negative penetration and PBP affinity?

• The C3′ vinyl group only
• The C7 acylamino side chain
• The C4 carboxylate methyl group
• The C11 keto group

Correct Answer: The C7 acylamino side chain

Q9. What is the main purpose of adding a β-lactamase inhibitor (e.g., clavulanic acid) to a β-lactam antibiotic?

• To inhibit bacterial protein synthesis
• To irreversibly inhibit β-lactamase and protect the antibiotic from hydrolysis
• To increase macrolide ribosomal binding
• To chelate divalent cations and disrupt cell wall assembly

Correct Answer: To irreversibly inhibit β-lactamase and protect the antibiotic from hydrolysis

Q10. Which core biosynthetic machinery constructs the macrolactone ring in erythromycin biosynthesis?

• Nonribosomal peptide synthetase (NRPS)
• Type I modular polyketide synthase (PKS)
• Ribosomal peptide synthesis followed by cyclization
• Shikimate pathway enzymes

Correct Answer: Type I modular polyketide synthase (PKS)

Q11. Which modification converts a macrolide into a ketolide and enhances binding to domain II of 23S rRNA?

• Removal of desosamine sugar
• Replacement of cladinose with a keto group at C3 and addition of bridged alkyl-aryl side chain
• Opening of the macrolactone ring to a linear ester
• Formation of a fused β-lactam ring at C6

Correct Answer: Replacement of cladinose with a keto group at C3 and addition of bridged alkyl-aryl side chain

Q12. Which structural property of carbapenems contributes to their broad-spectrum activity and β-lactamase resistance?

• An exocyclic methylene at C2 and absence of sulfur in the fused ring
• Presence of a 14-membered lactone
• Glycosylation at C3 with desosamine
• Oxidation of the cladinose sugar

Correct Answer: An exocyclic methylene at C2 and absence of sulfur in the fused ring

Q13. Which method is commonly used to introduce chemical diversity at the macrolide C3 position for SAR studies?

• Selective glycosyltransferase-mediated addition of deoxy sugars
• Direct electrophilic aromatic substitution
• Radical polymerization at the lactone
• Base-catalyzed epimerization of the macrolide core

Correct Answer: Selective glycosyltransferase-mediated addition of deoxy sugars

Q14. Which structural change in penicillins increases resistance to gastric acid and enables oral activity (e.g., amoxicillin vs. benzylpenicillin)?

• Introduction of an electron-withdrawing acylamino side chain at C6 (e.g., amino group)
• Removal of the β-lactam carbonyl
• Attachment of desosamine to the penam nucleus
• Formation of a spiro-β-lactone bridge

Correct Answer: Introduction of an electron-withdrawing acylamino side chain at C6 (e.g., amino group)

Q15. Which downstream enzymatic modification commonly decorates macrolides and affects pharmacokinetics and receptor binding?

• Halogenation of the β-lactam carbonyl
• Glycosylation with sugars like desosamine and cladinose
• Formation of a dihydrothiazine ring
• Peptidyl transferase-catalyzed N-methylation of PBPs

Correct Answer: Glycosylation with sugars like desosamine and cladinose

Q16. Which modification in third-generation cephalosporins increases activity against Gram-negative bacteria by improving outer membrane penetration?

• Bulky lipophilic side chain at C7
• Anionic or polar side chain at C3 that mimics diaminopimelic acid
• Replacement of β-lactam with lactone
• Glycosylation with desosamine

Correct Answer: Anionic or polar side chain at C3 that mimics diaminopimelic acid

Q17. Which resistance mechanism specifically reduces macrolide binding by methylation of 23S rRNA, and which gene encodes it?

• Efflux pump mediated by mecA
• Methylation of 23S rRNA by Erm methyltransferases encoded by erm genes
• β-lactamase production by bla genes
• Target mutation in gyrA gene

Correct Answer: Methylation of 23S rRNA by Erm methyltransferases encoded by erm genes

Q18. Which chemical modification is routinely performed on penicillin core to create long-acting benzathine penicillins?

• Formation of a salt with a bulky diamine (e.g., benzathine) to reduce solubility
• Oxidation to a cephalosporin nucleus
• Glycosylation with cladinose
• Conversion of the β-lactam to a β-lactone

Correct Answer: Formation of a salt with a bulky diamine (e.g., benzathine) to reduce solubility

Q19. Which synthetic approach is used to alter macrolide sugars selectively without disrupting the macrolactone core?

• Site-selective enzymatic glycosylation using glycosyltransferases or chemoenzymatic methods
• Global hydrogenation of the macrolactone double bonds
• Acid-catalyzed hydrolysis of the β-lactam
• Base-catalyzed ring expansion to a 16-membered ring

Correct Answer: Site-selective enzymatic glycosylation using glycosyltransferases or chemoenzymatic methods

Q20. Which structural element in monobactams accounts for their narrow spectrum and lack of cross-reactivity with penicillin-allergic patients?

• A single monocyclic β-lactam ring without fused bicyclic system and a sulfonic acid side chain
• A fused thiazolidine-β-lactam bicyclic core
• Glycosylated macrolactone attached to a β-lactam
• Large desosamine sugar conferring cross-reactivity

Correct Answer: A single monocyclic β-lactam ring without fused bicyclic system and a sulfonic acid side chain

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