Structure–activity relationship (SAR) of quinolones examines how substitutions at positions like N1, C6, C7 and C8 alter antibacterial spectrum, potency, pharmacokinetics and safety. For B.Pharm students, grasping the core C3–carboxyl/C4–keto scaffold, the effect of C6 fluorination, C7 heterocycles and C8 modifications clarifies generational differences (nalidixic acid → ciprofloxacin → levofloxacin → moxifloxacin) and clinical profiles. The mechanism involves inhibition of DNA gyrase and topoisomerase IV, producing lethal DNA breaks. Key practical topics include resistance mechanisms (gyrA/parC mutations, qnr, efflux), PK/PD (AUC/MIC), adverse effects (tendon injury, QT prolongation, phototoxicity) and cation chelation interactions. ‘Now let’s test your knowledge with 30 MCQs on this topic.’
Q1. Which structural features are essential for the basic antibacterial activity of quinolones?
- Aromatic bicyclic core with C3 carboxyl and C4 keto groups
- Phenolic OH and an amide linkage
- Sulfhydryl group and tertiary amine
- Long aliphatic chain with ester moiety
Correct Answer: Aromatic bicyclic core with C3 carboxyl and C4 keto groups
Q2. What is the primary effect of a fluorine atom at the C6 position in quinolones?
- Decreases plasma protein binding
- Increases antibacterial potency and cell penetration
- Prevents renal excretion
- Causes irreversible hepatotoxicity
Correct Answer: Increases antibacterial potency and cell penetration
Q3. Substitution at the C7 position with a piperazinyl ring most commonly improves which property?
- Activity against anaerobes
- Antipseudomonal and Gram-negative activity
- Reduction of QT prolongation risk
- Hepatic metabolism rate
Correct Answer: Antipseudomonal and Gram-negative activity
Q4. How does an 8-methoxy substitution (as in moxifloxacin) influence quinolone activity?
- Increases phototoxicity dramatically
- Enhances Gram-positive and anaerobic activity and reduces resistance development
- Eliminates renal clearance
- Blocks DNA gyrase binding entirely
Correct Answer: Enhances Gram-positive and anaerobic activity and reduces resistance development
Q5. Which N1 substituent is associated with increased Gram-negative potency (seen in ciprofloxacin)?
- Cyclopropyl group
- Methyl ester
- Long alkyl chain
- Phenyl sulfate
Correct Answer: Cyclopropyl group
Q6. According to common generation classification, which drug is considered a third-generation quinolone?
- Nalidixic acid
- Ciprofloxacin
- Levofloxacin
- Norfloxacin
Correct Answer: Levofloxacin
Q7. What is the primary molecular mechanism of action of quinolones?
- Inhibition of cell wall transpeptidase
- Inhibition of DNA gyrase and topoisomerase IV leading to double-strand DNA breaks
- Blockade of 30S ribosomal subunit
- Interference with folate synthesis
Correct Answer: Inhibition of DNA gyrase and topoisomerase IV leading to double-strand DNA breaks
Q8. Which enzyme is usually the primary target for fluoroquinolones in Gram-negative bacteria?
- Topoisomerase IV
- DNA gyrase (gyrase)
- DNA polymerase I
- RNA polymerase
Correct Answer: DNA gyrase (gyrase)
Q9. Quinolone antibacterial killing is best described as:
- Bacteriostatic and time-dependent
- Bactericidal and concentration-dependent
- Bacteriostatic and concentration-dependent
- Bactericidal and strictly time-dependent
Correct Answer: Bactericidal and concentration-dependent
Q10. The most common chromosomal mutations conferring quinolone resistance occur in which genes?
- pbp2 and pbp3
- gyrA/gyrB and parC/parE
- rpoB and rpoC
- erm and mef genes
Correct Answer: gyrA/gyrB and parC/parE
Q11. What is the function of plasmid-mediated qnr proteins in quinolone resistance?
- Act as efflux pumps to remove drug
- Protect DNA gyrase and topoisomerase IV from quinolones
- Enzymatically acetylate quinolones
- Chelate divalent cations to inactivate the drug
Correct Answer: Protect DNA gyrase and topoisomerase IV from quinolones
Q12. Efflux pump–mediated resistance to quinolones commonly involves which system in Enterobacteriaceae?
- MexAB-OprM
- AcrAB-TolC
- P-glycoprotein
- NorA
Correct Answer: AcrAB-TolC
Q13. Why do antacids and dairy products reduce oral absorption of fluoroquinolones?
- They change gastric pH to inactivate the drug
- They form chelates with quinolones via divalent/trivalent cations
- They induce first-pass hepatic metabolism
- They increase intestinal motility clearing drug faster
Correct Answer: They form chelates with quinolones via divalent/trivalent cations
Q14. Which adverse effect is classically associated with fluoroquinolones, especially in elderly patients?
- Excessive hair growth
- Tendonitis and risk of tendon rupture
- Hypoglycemia as a universal effect
- Profound neutropenia
Correct Answer: Tendonitis and risk of tendon rupture
Q15. Phototoxicity with some quinolones is linked to substitutions at which position?
- N1 position
- C3 position
- C8 position (e.g., halogens)
- C4 position
Correct Answer: C8 position (e.g., halogens)
Q16. Which fluoroquinolone has a relatively higher risk of QT interval prolongation and should be used cautiously with other QT-prolonging drugs?
- Ciprofloxacin
- Nalidixic acid
- Moxifloxacin
- Norfloxacin
Correct Answer: Moxifloxacin
Q17. Which quinolone relies more on hepatic metabolism for elimination compared to others?
- Ciprofloxacin (primarily renal)
- Levofloxacin (primarily renal)
- Moxifloxacin (significant hepatic metabolism)
- Ofloxacin (exclusively biliary)
Correct Answer: Moxifloxacin (significant hepatic metabolism)
Q18. The zwitterionic character of many fluoroquinolones arises from which groups?
- Phenol and amide
- Carboxylate (C3) and basic amine (e.g., piperazine at C7)
- Sulfate and hydroxyl
- Thiol and ester
Correct Answer: Carboxylate (C3) and basic amine (e.g., piperazine at C7)
Q19. Later-generation fluoroquinolones typically show improved activity against which organisms compared to early quinolones?
- Obligate intracellular parasites only
- Gram-positive cocci and atypical respiratory pathogens
- Fungi and viruses
- Strict anaerobes exclusively
Correct Answer: Gram-positive cocci and atypical respiratory pathogens
Q20. Which pharmacodynamic parameter best correlates with clinical efficacy of fluoroquinolones?
- Peak/MIC only
- T>MIC (time above MIC)
- AUC/MIC (area under curve to MIC ratio)
- Volume of distribution
Correct Answer: AUC/MIC (area under curve to MIC ratio)
Q21. The post-antibiotic effect (PAE) of fluoroquinolones refers to:
- The immediate allergic reaction after dosing
- Persistent suppression of bacterial growth after short exposure to drug
- Enhanced renal clearance after multiple doses
- Secondary infection risk following therapy
Correct Answer: Persistent suppression of bacterial growth after short exposure to drug
Q22. Which structural modification is especially associated with increased anaerobic activity?
- C6 fluorine alone
- C8 methoxy substitution
- N1 methylation
- Removal of C3 carboxyl
Correct Answer: C8 methoxy substitution
Q23. Which clinical adverse effect led regulatory agencies to restrict use of some fluoroquinolones for uncomplicated infections?
- Transient alopecia
- Irreversible peripheral neuropathy and disabling musculoskeletal effects
- Vitamin B12 deficiency
- Hyperprolactinemia
Correct Answer: Irreversible peripheral neuropathy and disabling musculoskeletal effects
Q24. Formation of the quinolone–enzyme–DNA complex prevents which step in the normal topoisomerase reaction?
- Initial DNA binding of topoisomerase
- Cleavage of one strand of DNA
- Re-ligation (resealing) of cleaved DNA strands
- Synthesis of RNA primers
Correct Answer: Re-ligation (resealing) of cleaved DNA strands
Q25. Which of the following is NOT a fluoroquinolone because it lacks a fluorine atom at C6?
- Nalidixic acid
- Ciprofloxacin
- Levofloxacin
- Moxifloxacin
Correct Answer: Nalidixic acid
Q26. Which chemical requirement improves quinolone binding by chelating divalent metal ions at the target?
- Aromatic nitro group at C5
- C3 carboxyl and C4 keto forming a bidentate chelation site
- Long-chain ester at N1
- Alkyl halide at C2
Correct Answer: C3 carboxyl and C4 keto forming a bidentate chelation site
Q27. Which C7 modification is most associated with high antipseudomonal activity?
- Piperazinyl or related basic heterocycles
- Long-chain alkyl ester
- Hydroxyl group
- Nitroimidazole ring
Correct Answer: Piperazinyl or related basic heterocycles
Q28. Mutations in which region of gyrA typically reduce quinolone binding and confer resistance?
- Peptidoglycan-binding domain
- Quinolone resistance-determining region (QRDR) of gyrA
- Ribosomal RNA binding site
- Pilin assembly locus
Correct Answer: Quinolone resistance-determining region (QRDR) of gyrA
Q29. Which fluoroquinolone is commonly used as a respiratory quinolone because of strong activity against Streptococcus pneumoniae and atypicals?
- Ciprofloxacin
- Levofloxacin
- Nalidixic acid
- Trimethoprim-sulfamethoxazole
Correct Answer: Levofloxacin
Q30. Which drug interaction is most clinically significant for oral fluoroquinolones that reduces their bioavailability?
- Coadministration with rifampicin inducing metabolism
- Concurrent antacids or supplements containing calcium, magnesium or iron
- Simultaneous opioid analgesics
- Co-prescription with beta-lactam antibiotics
Correct Answer: Concurrent antacids or supplements containing calcium, magnesium or iron
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.
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