Tetracycline antibiotics – classification and SAR MCQs With Answer

Tetracycline antibiotics – classification and SAR MCQs With Answer provide B.Pharm students with a focused review of tetracycline chemistry, classification, and structure–activity relationships (SAR). This introduction explains how core naphthacene ring modifications (C-5 to C-9 substitutions), chelation with divalent cations, and lipophilicity influence activity, spectrum, resistance, pharmacokinetics, and toxicity. Key compounds — tetracycline, doxycycline, minocycline, and glycylcycline (tigecycline) — illustrate clinical differences, Gram-positive and Gram-negative coverage, intracellular penetration, and common resistance mechanisms (efflux pumps, ribosomal protection). Understanding SAR guides rational drug design and clinical use. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which structural feature is essential for tetracycline binding to the bacterial 30S ribosomal subunit?

• The dimethylamino group at C-4
• The hydroxyl group at C-6
• The methyl group at C-2
• The keto-enol system on the A and C rings

Correct Answer: The dimethylamino group at C-4

Q2. Tetracyclines primarily inhibit bacterial growth by:

• Inhibiting cell wall synthesis
• Disrupting DNA gyrase
• Blocking initiation of protein synthesis by preventing aminoacyl-tRNA binding to the 30S subunit
• Increasing cell membrane permeability

Correct Answer: Blocking initiation of protein synthesis by preventing aminoacyl-tRNA binding to the 30S subunit

Q3. Which modification improves oral bioavailability and reduces chelation with divalent cations among tetracyclines?

• Conversion to a glycylcycline
• Removal of the C-4 dimethylamino group
• Introduction of a hydroxyl at C-6
• Making the molecule more lipophilic (e.g., minocycline)

Correct Answer: Making the molecule more lipophilic (e.g., minocycline)

Q4. Which tetracycline is least affected by renal impairment and is primarily excreted via the bile?

• Tetracycline
• Doxycycline
• Oxytetracycline
• Chlortetracycline

Correct Answer: Doxycycline

Q5. Glycylcycline (tigecycline) differs from classic tetracyclines mainly by:

• Lack of a tetracyclic core
• Attachment of a glycylamido moiety at C-9
• Removal of the keto-enol system
• Increased chelation with calcium

Correct Answer: Attachment of a glycylamido moiety at C-9

Q6. Which resistance mechanism reduces tetracycline intracellular concentration by active export?

• Ribosomal methylation
• Beta-lactamase production
• Efflux pumps
• Altered porin channels

Correct Answer: Efflux pumps

Q7. SAR studies show that epimerization at C-4 (formation of 4-epitetracycline) leads to:

• Increased antibacterial activity
• No change in activity
• Loss of antibacterial activity
• Conversion to a glycopeptide-like mechanism

Correct Answer: Loss of antibacterial activity

Q8. Chelation of tetracyclines with divalent cations (Ca2+, Mg2+) mainly results in:

• Enhanced absorption from the gut
• Formation of insoluble complexes reducing absorption
• Increased serum half-life
• Enhanced renal clearance

Correct Answer: Formation of insoluble complexes reducing absorption

Q9. Phototoxicity associated with some tetracyclines is related to:

• Ability to intercalate DNA
• Generation of reactive oxygen species upon UV exposure
• Inhibition of cytochrome P450 enzymes
• Excessive renal accumulation

Correct Answer: Generation of reactive oxygen species upon UV exposure

Q10. Which substituent is commonly associated with enhanced activity against Gram-negative organisms?

• Bulky substituent at C-7 improving membrane penetration
• Removal of C-6 hydroxyl group
• Glycosylation of C-2 position
• Loss of the 4-dimethylamino group

Correct Answer: Bulky substituent at C-7 improving membrane penetration

Q11. The major pharmacological difference between doxycycline and tetracycline is:

• Doxycycline has poor oral absorption
• Doxycycline has longer half-life and better tissue penetration
• Tetracycline is less likely to cause teeth discoloration
• Tetracycline is primarily hepatically cleared

Correct Answer: Doxycycline has longer half-life and better tissue penetration

Q12. Ribosomal protection proteins confer tetracycline resistance by:

• Enzymatic degradation of tetracyclines
• Methylating 16S rRNA to prevent binding
• Binding to the ribosome and displacing tetracycline
• Sequestering tetracycline in the periplasm

Correct Answer: Binding to the ribosome and displacing tetracycline

Q13. Which tetracycline derivative is known for the highest lipophilicity and good CNS penetration among traditional agents?

• Tetracycline
• Doxycycline
• Minocycline
• Oxytetracycline

Correct Answer: Minocycline

Q14. A key SAR requirement for antibacterial activity is the presence of:

• An intact tetracyclic naphthacene core
• Free sulfhydryl group at C-3
• A disulfide bridge between rings A and D
• A glucuronide moiety at C-7

Correct Answer: An intact tetracyclic naphthacene core

Q15. Which clinical concern is most associated with tetracycline use in children and pregnant women?

• Nephrotoxicity
• Permanent tooth discoloration and enamel hypoplasia
• Hepatic necrosis
• Ototoxicity

Correct Answer: Permanent tooth discoloration and enamel hypoplasia

Q16. Substitution at C-9 in glycylcyclines primarily overcomes resistance due to:

• Ribosomal methylation
• Enzymatic hydrolysis
• Efflux pumps and ribosomal protection
• Altered drug metabolism

Correct Answer: Efflux pumps and ribosomal protection

Q17. Which property of tetracyclines contributes to their activity against intracellular pathogens like Chlamydia?

• Poor tissue penetration
• Strong binding to plasma proteins only
• Good intracellular accumulation due to lipophilicity
• Exclusive activity in acidic environments

Correct Answer: Good intracellular accumulation due to lipophilicity

Q18. Which functional group is involved in forming the keto-enol tautomeric system important for metal chelation?

• Amino group at C-4
• Carboxyl group at C-1
• Keto and enol groups at C-11 and C-12 (rings A/C region)
• Sulfhydryl at C-3

Correct Answer: Keto and enol groups at C-11 and C-12 (rings A/C region)

Q19. Tigecycline shows activity against many tetracycline-resistant bacteria because it:

• Is rapidly excreted renally
• Has higher ribosomal affinity and evades efflux pumps
• Lacks the tetracyclic core
• Inhibits cell wall synthesis in addition to protein synthesis

Correct Answer: Has higher ribosomal affinity and evades efflux pumps

Q20. Which factor increases the risk of esophageal irritation with oral tetracyclines?

• Taking with a full glass of water
• Taking immediately before lying down
• Taking with milk
• Taking with antacids

Correct Answer: Taking immediately before lying down

Q21. Which statement about minocycline’s adverse effects is correct?

• It has no risk of vestibular toxicity
• It is commonly associated with dizziness and vertigo
• It causes hypoglycemia in most patients
• It never causes autoimmune-type syndromes

Correct Answer: It is commonly associated with dizziness and vertigo

Q22. The presence of a 7-dimethylamino or similar substituent generally influences tetracycline activity by:

• Reducing ribosomal binding affinity
• Improving activity against tetracycline-susceptible strains and affecting spectrum
• Eliminating chelation ability
• Mediating enzymatic degradation

Correct Answer: Improving activity against tetracycline-susceptible strains and affecting spectrum

Q23. Which laboratory phenomenon is commonly observed when tetracyclines are exposed to humid heat or oxygen, affecting potency?

• Hydrolysis to active metabolites
• Photooxidation and epimerization leading to degradation
• Conversion to more lipophilic forms
• Glycosylation increasing activity

Correct Answer: Photooxidation and epimerization leading to degradation

Q24. In SAR context, increased lipophilicity of tetracyclines tends to:

• Decrease tissue penetration
• Enhance penetration into Gram-negative outer membrane and tissues
• Eliminate activity against intracellular pathogens
• Promote faster renal excretion

Correct Answer: Enhance penetration into Gram-negative outer membrane and tissues

Q25. Which tetracycline is commonly used as the reference natural product in SAR comparisons?

• Doxycycline
• Tetracycline (parent compound)
• Minocycline
• Tigecycline

Correct Answer: Tetracycline (parent compound)

Q26. Which statement correctly describes tetracycline interactions with antacids?

• Antacids increase tetracycline absorption
• Antacids form chelates with tetracyclines, reducing absorption
• Antacids convert tetracyclines to more active forms
• Antacids have no clinically relevant interaction

Correct Answer: Antacids form chelates with tetracyclines, reducing absorption

Q27. Which modification is associated with reduced susceptibility to enzymatic inactivation for newer tetracyclines?

• Removal of all hydroxyl groups
• Bulky substitutions that sterically hinder inactivating enzymes
• Increased polarity to enhance renal excretion
• Addition of sulfate groups

Correct Answer: Bulky substitutions that sterically hinder inactivating enzymes

Q28. Which clinical use best reflects tetracycline’s spectrum and intracellular activity?

• First-line for Pseudomonas aeruginosa bacteremia
• Treatment of atypical pneumonias (Mycoplasma, Chlamydia) and acne
• Exclusive use for fungal infections
• Only topical antiviral therapy

Correct Answer: Treatment of atypical pneumonias (Mycoplasma, Chlamydia) and acne

Q29. Which pharmacokinetic property differentiates doxycycline from tetracycline, influencing dosing frequency?

• Doxycycline has a shorter half-life requiring more frequent dosing
• Doxycycline has a longer half-life allowing once- or twice-daily dosing
• Tetracycline is completely metabolized on first pass
• Tetracycline penetrates the CNS better than doxycycline

Correct Answer: Doxycycline has a longer half-life allowing once- or twice-daily dosing

Q30. Which SAR insight guided the development of tigecycline to overcome resistance?

• Removing the naphthacene core to avoid binding sites
• Adding a glycylamido moiety at C-9 to enhance ribosomal binding and bypass efflux
• Eliminating all hydroxyl groups to prevent chelation
• Reducing molecular size to avoid immune detection

Correct Answer: Adding a glycylamido moiety at C-9 to enhance ribosomal binding and bypass efflux

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