Structure activity relationship of antibiotics MCQs With Answer

Structure activity relationship of antibiotics MCQs With Answer

The structure–activity relationship (SAR) of antibiotics explores how changes in chemical structure influence antibacterial potency, spectrum, pharmacokinetics, and resistance. For B. Pharm students, understanding SAR is essential for rational drug design, predicting mechanism of action, and optimizing properties such as lipophilicity, pKa, steric hindrance, and target binding. Key concepts include pharmacophores, ring substitutions (e.g., beta-lactam side chains), bioisosteres, and modifications that overcome efflux or enzymatic degradation. Mastery of SAR helps explain clinical activity differences among beta-lactams, macrolides, quinolones, aminoglycosides, tetracyclines, glycopeptides, and newer classes. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which structural feature is essential for the antibacterial activity of beta-lactam antibiotics?

• Presence of a chlorinated aromatic ring
• Beta-lactam four-membered cyclic amide ring
• Multiple hydroxyl groups on a sugar moiety
• Long fatty acyl side chain only

Correct Answer: Beta-lactam four-membered cyclic amide ring

Q2. In penicillins, modification of the 6-APA side chain primarily affects which property?

• Ability to chelate metal ions
• Gram-negative outer membrane penetration
• Beta-lactamase stability and spectrum
• Interaction with 50S ribosomal subunit

Correct Answer: Beta-lactamase stability and spectrum

Q3. For fluoroquinolones, substitution at the C-6 position (fluorine) mainly increases:

• Binding to 30S ribosome
• DNA gyrase/topoisomerase inhibition potency and cell penetration
• Glycopeptide-like activity
• Hydrolysis by beta-lactamases

Correct Answer: DNA gyrase/topoisomerase inhibition potency and cell penetration

Q4. Which SAR principle explains why aminoglycosides require multiple amino sugars for activity?

• They form covalent bonds with cell wall precursors
• Multiple positively charged amines enhance binding to the negatively charged bacterial ribosomal RNA
• Sugar moieties increase lipophilicity for membrane diffusion
• Aromatic rings mediate DNA intercalation

Correct Answer: Multiple positively charged amines enhance binding to the negatively charged bacterial ribosomal RNA

Q5. Macrolide activity is most dependent on which structural feature?

• Macrocyclic lactone ring and sugar residues attached at specific positions
• Presence of a beta-lactam ring
• Multiple halogen atoms on an aromatic core
• Terminal guanidino group

Correct Answer: Macrocyclic lactone ring and sugar residues attached at specific positions

Q6. Tetracycline SAR: the dimethylamino group at C-4 primarily influences:

• Binding to D-Ala-D-Ala cell wall precursors
• Ribosomal binding and antibacterial potency; epimerization reduces activity
• Inhibition of DNA gyrase
• Glycosylation by bacterial enzymes

Correct Answer: Ribosomal binding and antibacterial potency; epimerization reduces activity

Q7. Glycopeptide antibiotics (e.g., vancomycin) bind to which target motif, and which structural class enables this binding?

• D-Ala-D-Ala termini of peptidoglycan; large glycosylated peptide scaffold
• 50S ribosomal RNA; macrolide lactone ring
• DNA gyrase; fluoroquinolone core
• Lipid II membrane anchor; aminoglycoside sugars

Correct Answer: D-Ala-D-Ala termini of peptidoglycan; large glycosylated peptide scaffold

Q8. Addition of bulky side chains near the beta-lactam ring in cephalosporins is used to:

• Enhance ribosomal binding
• Reduce susceptibility to beta-lactamases and alter spectrum
• Increase DNA intercalation
• Promote renal excretion only

Correct Answer: Reduce susceptibility to beta-lactamases and alter spectrum

Q9. Which modification commonly increases oral bioavailability of antibiotic prodrugs?

• Converting charged carboxylates to ester prodrugs to improve lipophilicity
• Adding multiple charged amines
• Removing all aromatic rings
• Increasing molecular weight above 1000 Da

Correct Answer: Converting charged carboxylates to ester prodrugs to improve lipophilicity

Q10. Polymyxin antibiotics rely on which SAR attribute for activity against Gram-negative bacteria?

• Hydrophobic tail and multiple cationic residues that disrupt LPS and membranes
• Beta-lactam ring binding PBP
• Inhibition of folate synthesis through para-aminobenzoic acid mimicry
• Bacterial DNA cleavage via intercalating planar rings

Correct Answer: Hydrophobic tail and multiple cationic residues that disrupt LPS and membranes

Q11. Which SAR change in macrolides confers improved acid stability and oral absorption (as in azithromycin)?

• Insertion of a nitrogen into the macrocyclic ring (15-membered azalide)
• Removal of all sugar residues
• Hydrogenation of the lactone carbonyl to alcohol
• Addition of a beta-lactam ring

Correct Answer: Insertion of a nitrogen into the macrocyclic ring (15-membered azalide)

Q12. For fluoroquinolones, substitution at the N-1 and C-7 positions mainly affects:

• Interaction with ribosomal A-site
• Pharmacokinetics and spectrum, especially Gram-negative activity and efflux susceptibility
• Peptidoglycan cross-linking
• Glycopeptide binding to D-Ala-D-Ala

Correct Answer: Pharmacokinetics and spectrum, especially Gram-negative activity and efflux susceptibility

Q13. Sulfonamide antibacterial activity is based on structural mimicry of which endogenous substrate?

• Para-aminobenzoic acid (PABA), inhibiting dihydropteroate synthase
• D-Ala-D-Ala, inhibiting transpeptidase
• ATP, inhibiting gyrase
• Peptidoglycan pentapeptide

Correct Answer: Para-aminobenzoic acid (PABA), inhibiting dihydropteroate synthase

Q14. Which structural modification of aminoglycosides commonly leads to reduced susceptibility to bacterial modifying enzymes?

• Removal of all amino groups
• Incorporation of bulky substituents or novel linkages to block enzyme access
• Converting into a beta-lactam scaffold
• Adding multiple chlorine atoms

Correct Answer: Incorporation of bulky substituents or novel linkages to block enzyme access

Q15. The zwitterionic nature of some antibiotics (e.g., carbapenems) influences which property?

• Exact ribosomal binding pocket only
• Enhanced penetration through porins and broad Gram-negative activity
• Exclusive activity against anaerobes
• Conversion to active metabolite by esterases

Correct Answer: Enhanced penetration through porins and broad Gram-negative activity

Q16. Oxazolidinone antibiotics (e.g., linezolid) act by binding to which ribosomal site and which SAR element is critical?

• 50S peptidyl transferase center; a substituted heterocyclic core (oxazolidinone) essential for binding
• 30S A-site; aminoglycoside sugars essential
• DNA gyrase; bicyclic quinolone core essential
• Cell membrane lipids; lipopeptide tail essential

Correct Answer: 50S peptidyl transferase center; a substituted heterocyclic core (oxazolidinone) essential for binding

Q17. SAR of lipopeptides (e.g., daptomycin): the cyclic peptide core and lipid tail primarily determine:

• Ribosomal decoding accuracy
• Membrane insertion, depolarization, and bactericidal activity
• Folate pathway inhibition
• Peptidoglycan cross-linking

Correct Answer: Membrane insertion, depolarization, and bactericidal activity

Q18. Which physicochemical property, influenced by SAR, often enhances intracellular accumulation in bacteria?

• Extremely high molecular weight (>2000 Da)
• Balanced lipophilicity and presence of polar groups enabling diffusion and retention
• Complete neutrality with no polar surface area
• High aromaticity without ionizable groups

Correct Answer: Balanced lipophilicity and presence of polar groups enabling diffusion and retention

Q19. Modifying the carboxylate group in some antibiotics to an ester prodrug primarily affects:

• Target binding affinity but not absorption
• Oral absorption and membrane permeability, converted in vivo to active acid
• Increasing beta-lactamase hydrolysis
• Permanent loss of activity

Correct Answer: Oral absorption and membrane permeability, converted in vivo to active acid

Q20. Which SAR change in quinolones is associated with an increased risk of tendon toxicity?

• Removal of the C-3 carboxylate
• Certain substitutions that increase overall tissue penetration and off-target interactions
• Adding glycosylated sugar moieties
• Converting to a cyclic peptide structure

Correct Answer: Certain substitutions that increase overall tissue penetration and off-target interactions

Q21. Resistance by target modification (e.g., methylation of 23S rRNA) reduces activity of which antibiotic class and what SAR strategy can help overcome it?

• Fluoroquinolones; remove fluorine to overcome resistance
• Macrolides; design ketolides or modify macrolide sugars to improve binding despite methylation
• Beta-lactams; increase beta-lactam ring strain to overcome methylation
• Sulfonamides; add bulky side chains to overcome methylation

Correct Answer: Macrolides; design ketolides or modify macrolide sugars to improve binding despite methylation

Q22. Which SAR consideration is critical when designing antibiotics to evade efflux pumps?

• Maximize positive charge to increase recognition by pumps
• Reduce recognition motifs (e.g., certain polar surface features) or increase size/hydrophobicity to avoid efflux
• Ensure complete metabolic stability so pumps cannot act
• Convert to a dipeptide structure exclusively

Correct Answer: Reduce recognition motifs (e.g., certain polar surface features) or increase size/hydrophobicity to avoid efflux

Q23. Which structural element is central to the activity of beta-lactamase inhibitors like clavulanic acid?

• A sulfonamide moiety mimicking PABA
• A strained β-lactam-like scaffold that can acylate and irreversibly inhibit beta-lactamases
• A long lipophilic tail for membrane disruption
• An aminoglycoside sugar core

Correct Answer: A strained β-lactam-like scaffold that can acylate and irreversibly inhibit beta-lactamases

Q24. In SAR studies, what does the term ‘pharmacophore’ refer to?

• The part of the molecule responsible for metabolism only
• The minimal ensemble of steric and electronic features necessary for optimal interactions with a biological target
• An unrelated solvent molecule in crystal structures
• The part of a drug that always causes toxicity

Correct Answer: The minimal ensemble of steric and electronic features necessary for optimal interactions with a biological target

Q25. Which SAR modification improved metronidazole-like nitroimidazole selectivity for anaerobes?

• Incorporation of bulky polar groups preventing reduction
• Structural features that favor enzymatic reductive activation under low-oxygen conditions
• Removing the nitro group entirely
• Conjugation to large proteins

Correct Answer: Structural features that favor enzymatic reductive activation under low-oxygen conditions

Q26. Which SAR principle explains why charged antibiotics have difficulty penetrating Gram-negative outer membrane unless they use porins?

• Charged molecules are more lipophilic and thus pass freely
• Hydrophilic and charged molecules cannot diffuse through lipid bilayers and rely on porins for entry
• Charge eliminates all protein binding
• Charged antibiotics are selectively transported by efflux pumps into the cell

Correct Answer: Hydrophilic and charged molecules cannot diffuse through lipid bilayers and rely on porins for entry

Q27. Which SAR modification converted chlortetracycline to doxycycline, improving pharmacokinetics?

• Removal of the C-6 hydroxyl group to increase lipophilicity and oral absorption
• Addition of a beta-lactam ring
• Glycosylation at multiple sites
• Halogenation of all aromatic rings

Correct Answer: Removal of the C-6 hydroxyl group to increase lipophilicity and oral absorption

Q28. Which SAR factor is most important for antibiotics that target intracellular pathogens?

• High plasma protein binding only
• Ability to cross host cell membranes: balance of lipophilicity and ionization for intracellular accumulation
• Extremely high molecular rigidity
• Complete absence of hydrogen bond donors

Correct Answer: Ability to cross host cell membranes: balance of lipophilicity and ionization for intracellular accumulation

Q29. In designing antibiotics to avoid rapid renal clearance, which SAR adjustment is commonly used?

• Decrease molecular size below 50 Da
• Increase plasma protein binding or add steric bulk to reduce glomerular filtration
• Increase water solubility to extreme levels
• Eliminate all polar functional groups

Correct Answer: Increase plasma protein binding or add steric bulk to reduce glomerular filtration

Q30. Which SAR insight helped develop ceftaroline, a cephalosporin active against MRSA?

• Removing all side chains to reduce size
• Designing a side chain that allows binding to altered PBP2a active site while retaining beta-lactam core
• Incorporating a glycopeptide scaffold into cephalosporin
• Conjugating a macrolide sugar to the cephalosporin nucleus

Correct Answer: Designing a side chain that allows binding to altered PBP2a active site while retaining beta-lactam core

G S Sachin

I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.

Mail- Sachin@pharmacyfreak.com