Understanding synthetic antitubercular agents is essential for B. Pharm students studying drug design, classification, and structure-activity relationships (SAR). This concise module covers major synthetic and semi-synthetic antitubercular classes — isoniazid, ethambutol, pyrazinamide, fluoroquinolones, cycloserine, para-aminosalicylic acid, bedaquiline, delamanid and others — linking chemical scaffolds to mechanisms of action, activation (prodrugs), resistance mechanisms, pharmacophore features, lipophilicity and toxicity. Emphasis on SAR highlights key functional groups (hydrazide, nitroimidazole, diarylquinoline, fluoroquinolone core) that influence mycobacterial cell wall penetration, enzyme targeting and adverse effects. Review of classification, pharmacology, and SAR will strengthen rational therapy choices and rational drug design. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. Which statement best defines “synthetic antitubercular agents”?
- Chemical compounds synthesized in the laboratory specifically designed to treat tuberculosis
- Natural antibiotics produced by soil bacteria used against tuberculosis
- Vaccines derived from attenuated Mycobacterium tuberculosis strains
- Herbal remedies traditionally used to relieve pulmonary symptoms
Correct Answer: Chemical compounds synthesized in the laboratory specifically designed to treat tuberculosis
Q2. Which group lists the usual first-line antitubercular drugs used in standard therapy?
- Isoniazid, Rifampicin, Pyrazinamide, Ethambutol
- Ciprofloxacin, Amikacin, Cycloserine, PAS
- Bedaquiline, Linezolid, Delamanid, Clofazimine
- Streptomycin, Gentamicin, Vancomycin, Daptomycin
Correct Answer: Isoniazid, Rifampicin, Pyrazinamide, Ethambutol
Q3. How does isoniazid primarily exert its antitubercular action?
- Inhibition of mycolic acid synthesis after activation by KatG catalase-peroxidase
- Inhibition of DNA-dependent RNA polymerase by binding to the β-subunit
- Direct disruption of the mycobacterial cell membrane by detergent action
- Inhibition of topoisomerase IV without needing metabolic activation
Correct Answer: Inhibition of mycolic acid synthesis after activation by KatG catalase-peroxidase
Q4. Which functional group in isoniazid is critical for its activity and prodrug behavior?
- Hydrazide (–CONHNH2)
- Carboxylic acid (–COOH)
- Thiol (–SH)
- Ether linkage (–O–)
Correct Answer: Hydrazide (–CONHNH2)
Q5. Pyrazinamide is most active under which condition and requires which enzyme for activation?
- Acidic pH and activation by pyrazinamidase (PncA)
- Neutral pH and activation by KatG
- Basic pH and activation by Ddn nitroreductase
- Hypoxic conditions without enzymatic activation
Correct Answer: Acidic pH and activation by pyrazinamidase (PncA)
Q6. What is the main molecular target of ethambutol in Mycobacterium tuberculosis?
- Arabinofuranosyl transferases (Emb proteins) involved in arabinogalactan synthesis
- DNA gyrase (gyrA/gyrB)
- ATP synthase complex
- RNA polymerase β-subunit
Correct Answer: Arabinofuranosyl transferases (Emb proteins) involved in arabinogalactan synthesis
Q7. Rifampicin inhibits mycobacterial growth primarily by which mechanism?
- Binding to DNA-dependent RNA polymerase and blocking RNA synthesis initiation
- Inhibiting peptidoglycan cross-linking by binding transpeptidase
- Cleaving mycolic acids in the cell wall
- Disrupting ribosomal 30S subunit function
Correct Answer: Binding to DNA-dependent RNA polymerase and blocking RNA synthesis initiation
Q8. Fluoroquinolones act against Mycobacterium tuberculosis by inhibiting which enzymes?
- DNA gyrase and topoisomerase IV
- RNA polymerase and ribonuclease
- Mycolic acid synthase complex
- ATP synthase and cytochrome oxidase
Correct Answer: DNA gyrase and topoisomerase IV
Q9. Which novel antitubercular drug belongs to the diarylquinoline class and targets mycobacterial ATP synthase?
- Bedaquiline
- Linezolid
- Ethambutol
- Pyrazinamide
Correct Answer: Bedaquiline
Q10. Delamanid and pretomanid belong to which chemical class and require what for activation?
- Nitroimidazoles activated by mycobacterial nitroreductases under anaerobic conditions
- Macrolides activated by hepatic CYP3A4
- Beta-lactams activated by bacterial transpeptidases
- Peptide antibiotics activated by peptidases in macrophages
Correct Answer: Nitroimidazoles activated by mycobacterial nitroreductases under anaerobic conditions
Q11. In fluoroquinolone SAR, which substitution is most associated with increased antibacterial potency?
- Fluorine at C-6 of the quinolone core
- Methyl at the carboxyl group
- Hydroxyl at C-4 only
- Sulfhydryl group on the aromatic ring
Correct Answer: Fluorine at C-6 of the quinolone core
Q12. Which structural feature of rifamycins is essential for high affinity binding to RNA polymerase?
- An ansa (bridge) chain connecting aromatic moieties and the naphthohydroquinone core
- A simple benzene ring without substituents
- A linear aliphatic chain of >20 carbons
- An unsubstituted primary amine at the terminal position
Correct Answer: An ansa (bridge) chain connecting aromatic moieties and the naphthohydroquinone core
Q13. Para-aminosalicylic acid (PAS) primarily acts as:
- An antimetabolite interfering with folate synthesis in Mycobacterium
- An inhibitor of RNA polymerase
- A membrane-disrupting cationic detergent
- An ATP synthase activator
Correct Answer: An antimetabolite interfering with folate synthesis in Mycobacterium
Q14. Cycloserine inhibits mycobacterial cell wall synthesis by blocking which enzymes?
- D-alanine racemase and D-alanine–D-alanine ligase
- Beta-lactamase and transglycosylase
- Mycolic acid synthase and enoyl reductase
- Ribosomal peptidyl transferase
Correct Answer: D-alanine racemase and D-alanine–D-alanine ligase
Q15. Which adverse effect is commonly associated with isoniazid and can be reduced by pyridoxine (vitamin B6) supplementation?
- Peripheral neuropathy
- Optic neuritis
- Nephrotoxicity
- Ototoxicity
Correct Answer: Peripheral neuropathy
Q16. Optic neuritis, presenting with decreased visual acuity and red-green color blindness, is a known toxicity of which antitubercular agent?
- Ethambutol
- Rifampicin
- Pyrazinamide
- Isoniazid
Correct Answer: Ethambutol
Q17. Which antitubercular drug commonly causes orange-red discoloration of body fluids and drug interactions via CYP induction?
- Rifampicin
- Bedaquiline
- Ethambutol
- Pyrazinamide
Correct Answer: Rifampicin
Q18. Which safety concern is particularly associated with bedaquiline therapy?
- QT interval prolongation and potential arrhythmia
- Severe ototoxicity leading to deafness
- Acute hemolytic anemia in G6PD deficiency
- Severe hyponatremia due to SIADH
Correct Answer: QT interval prolongation and potential arrhythmia
Q19. From an SAR perspective for antitubercular agents, why is increased lipophilicity often beneficial?
- Improves penetration through the lipid-rich mycobacterial cell wall and intracellular distribution
- Guarantees water solubility and rapid renal excretion
- Always reduces toxicity and increases metabolic stability
- Prevents binding to target enzymes and reduces potency
Correct Answer: Improves penetration through the lipid-rich mycobacterial cell wall and intracellular distribution
Q20. The most common molecular basis of isoniazid resistance in M. tuberculosis is:
- Mutations in the katG gene leading to reduced activation of the prodrug
- Efflux pump overexpression for pyrazinamide
- Alteration of peptidoglycan cross-linking enzymes
- Increased porin expression causing drug dilution
Correct Answer: Mutations in the katG gene leading to reduced activation of the prodrug
Q21. Resistance to rifampicin is most often due to mutations in which gene?
- rpoB (encoding the RNA polymerase β-subunit)
- gyrA (encoding DNA gyrase subunit A)
- pncA (pyrazinamidase)
- embB (arabinosyl transferase)
Correct Answer: rpoB (encoding the RNA polymerase β-subunit)
Q22. Which antitubercular drug is a prodrug activated by bacterial pyrazinamidase encoded by pncA?
- Pyrazinamide
- Isoniazid
- Rifampicin
- Ethambutol
Correct Answer: Pyrazinamide
Q23. Which structural feature in isoniazid and related hydrazides is implicated in hepatotoxicity risk?
- Hydrazide moiety capable of generating reactive metabolites
- Long aliphatic chain >12 carbons
- Quaternary ammonium center
- Polyethylene glycol conjugation
Correct Answer: Hydrazide moiety capable of generating reactive metabolites
Q24. In nitroimidazole antitubercular agents (delamanid, pretomanid), which group is essential for reductive activation and bactericidal action?
- Nitro (–NO2) group on the imidazole ring
- Primary alcohol group
- Thiophene ring fused to the imidazole
- Para-chloro substituent on an aromatic ring
Correct Answer: Nitro (–NO2) group on the imidazole ring
Q25. Which pair of drugs both inhibit mycolic acid synthesis (directly or via similar targets)?
- Isoniazid and Ethionamide
- Rifampicin and Pyrazinamide
- Ethambutol and Cycloserine
- Amikacin and Linezolid
Correct Answer: Isoniazid and Ethionamide
Q26. In fluoroquinolone SAR, substitution at which position often modulates spectrum and pharmacokinetics (e.g., piperazinyl group)?
- C-7
- C-2
- C-3
- C-1
Correct Answer: C-7
Q27. Which drug is correctly matched with its chemical class “diarylquinoline”?
- Bedaquiline
- Rifampicin
- Ethambutol
- Para-aminosalicylic acid
Correct Answer: Bedaquiline
Q28. Which antitubercular agent is an analogue of para-aminobenzoic acid (PABA) and acts as an antimetabolite?
- Para-aminosalicylic acid (PAS)
- Cycloserine
- Ethambutol
- Delamanid
Correct Answer: Para-aminosalicylic acid (PAS)
Q29. Which ring system is present in isoniazid and contributes to its interaction with mycobacterial enzymes?
- Pyridine ring (isoniazid = isonicotinic acid hydrazide)
- Indole ring system
- Benzodiazepine core
- Steroid fused-ring nucleus
Correct Answer: Pyridine ring (isoniazid = isonicotinic acid hydrazide)
Q30. Which of the following antitubercular drugs is classified as a second-line agent commonly used for drug-resistant TB?
- Cycloserine
- Isoniazid
- Rifampicin
- Pyrazinamide
Correct Answer: Cycloserine
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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