Chloroquine – synthesis and resistance MCQs With Answer

Chloroquine – synthesis and resistance MCQs With Answer

Chloroquine is a classic 4‑aminoquinoline antimalarial widely studied in medicinal chemistry and clinical pharmacy. This introduction covers chloroquine’s quinoline core synthesis (Skraup/Friedländer routes, introduction of 4‑chloro intermediate and nucleophilic side‑chain substitution), structure‑activity relationships (essential 4‑amino group, diethylamino side chain), pharmacokinetics, metabolism to desethylchloroquine, mechanism of action (inhibition of heme polymerization), and molecular basis of resistance (pfcrt K76T, pfmdr1 alterations, reduced vacuolar accumulation). It also highlights adverse effects, drug interactions and monitoring techniques relevant to B.Pharm students. Now let’s test your knowledge with 30 MCQs on this topic.

Q1. Which chemical class does chloroquine belong to?

• 4‑aminoquinoline derivative
• 8‑aminoquinoline derivative
• Phenothiazine derivative
• Artemisinin derivative

Correct Answer: 4‑aminoquinoline derivative

Q2. Which classical reaction is commonly used to construct the quinoline nucleus in chloroquine synthesis?

• Skraup synthesis
• Aldol condensation
• Buchwald–Hartwig amination
• Grignard addition

Correct Answer: Skraup synthesis

Q3. In the typical laboratory synthesis of chloroquine, how is the side chain introduced onto the quinoline core?

• Nucleophilic aromatic substitution on a 4‑chloroquinoline intermediate
• Electrophilic aromatic substitution at the 2‑position
• Radical addition to the quinoline ring
• Diels‑Alder cycloaddition followed by rearrangement

Correct Answer: Nucleophilic aromatic substitution on a 4‑chloroquinoline intermediate

Q4. Which position on the quinoline ring is the primary site for substitution by the chloroquine side chain?

• 4‑position
• 2‑position
• 6‑position
• 8‑position

Correct Answer: 4‑position

Q5. What is the principal antimalarial mechanism of action of chloroquine?

• Inhibition of heme polymerization to hemozoin in the parasite food vacuole
• Inhibition of dihydrofolate reductase
• Alkylation of parasite DNA
• Inhibition of parasite protein synthesis at the ribosome

Correct Answer: Inhibition of heme polymerization to hemozoin in the parasite food vacuole

Q6. Where does chloroquine primarily accumulate within Plasmodium parasites to exert its effect?

• Digestive vacuole (acidic food vacuole)
• Mitochondria
• Cytosol bound to ribosomes
• Plasma membrane

Correct Answer: Digestive vacuole (acidic food vacuole)

Q7. Which parasite gene mutation is most strongly associated with chloroquine resistance in Plasmodium falciparum?

• pfcrt K76T mutation
• dhfr S108N mutation
• cox1 G143A mutation
• pfk13 C580Y mutation

Correct Answer: pfcrt K76T mutation

Q8. The pfmdr1 gene contributes to chloroquine resistance mainly by:

• Altering transporter activity and copy number to modulate drug accumulation
• Direct enzymatic degradation of chloroquine
• Encoding a membrane pore for heme export
• Phosphorylating chloroquine to inactive forms

Correct Answer: Altering transporter activity and copy number to modulate drug accumulation

Q9. Chloroquine-resistant parasites often show cross-resistance with which related antimalarial?

• Amodiaquine
• Artemether‑lumefantrine
• Primaquine
• Atovaquone

Correct Answer: Amodiaquine

Q10. Which functional group on the quinoline ring is essential for chloroquine’s antimalarial activity?

• 4‑amino group
• 2‑nitro group
• 7‑hydroxy group
• 3‑carboxy group

Correct Answer: 4‑amino group

Q11. Major human metabolic pathway of chloroquine involves which process?

• Desethylation to desethylchloroquine by CYP enzymes
• Glucuronidation at the quinoline ring
• Sulfation of the 4‑amino group
• Direct renal excretion unchanged only

Correct Answer: Desethylation to desethylchloroquine by CYP enzymes

Q12. Which serious long‑term adverse effect is a key concern with chronic chloroquine therapy?

• Retinopathy leading to visual field defects
• Ototoxicity with irreversible deafness
• Severe nephrotoxicity with renal failure
• Acute pancreatitis

Correct Answer: Retinopathy leading to visual field defects

Q13. For malaria prophylaxis in non‑resistant areas, chloroquine is typically administered at which frequency?

• Once weekly
• Daily
• Once monthly
• Single dose before travel

Correct Answer: Once weekly

Q14. The long elimination half‑life of chloroquine is primarily due to:

• Extensive tissue binding and large volume of distribution
• Rapid renal excretion with high clearance
• Immediate metabolism to inactive polar metabolites
• Low oral bioavailability requiring re‑dosing

Correct Answer: Extensive tissue binding and large volume of distribution

Q15. Which moiety in chloroquine’s side chain is important for its accumulation in acidic vacuoles?

• Diethylamino tertiary amine
• Primary alcohol
• Carboxylic acid
• Nitro group

Correct Answer: Diethylamino tertiary amine

Q16. A common synthetic intermediate used for side‑chain introduction in chloroquine manufacture is:

• 4,7‑dichloroquinoline
• 2‑nitroaniline
• Quinoline N‑oxide
• 7‑hydroxyquinoline

Correct Answer: 4,7‑dichloroquinoline

Q17. Which agent has been shown in vitro to reverse chloroquine resistance by inhibiting efflux transporters?

• Verapamil
• Rifampicin
• Chlorpromazine
• Quinidine

Correct Answer: Verapamil

Q18. The cardiotoxic effects of overdose or chronic chloroquine use most commonly include:

• Conduction abnormalities and QT prolongation
• Aortic dissection
• Valvular stenosis
• Peripheral arterial thrombosis

Correct Answer: Conduction abnormalities and QT prolongation

Q19. Besides malaria, chloroquine is clinically used for which indication due to its immunomodulatory effects?

• Rheumatoid arthritis and systemic lupus erythematosus
• Type 2 diabetes mellitus
• Hypothyroidism
• Chronic obstructive pulmonary disease

Correct Answer: Rheumatoid arthritis and systemic lupus erythematosus

Q20. The main active metabolite of chloroquine detected in plasma is:

• Desethylchloroquine
• Hydroxychloroquine
• Chloroquine N‑oxide
• Chloroquine glucuronide

Correct Answer: Desethylchloroquine

Q21. Which analytical technique is commonly used in laboratories to quantify chloroquine in blood?

• High‑performance liquid chromatography (HPLC)
• Ninhydrin colorimetry
• Gravimetric analysis
• Flame photometry

Correct Answer: High‑performance liquid chromatography (HPLC)

Q22. Chloroquine resistance in P. falciparum typically results in what change in drug behavior at the cellular level?

• Reduced accumulation of drug within the parasite digestive vacuole
• Increased binding affinity to heme
• Enhanced conversion to active metabolites inside the parasite
• Inhibition of human CYP enzymes only

Correct Answer: Reduced accumulation of drug within the parasite digestive vacuole

Q23. The pfcrt gene that mediates chloroquine resistance is located on which Plasmodium falciparum chromosome?

• Chromosome 7
• Chromosome 1
• Chromosome 13
• Chromosome 9

Correct Answer: Chromosome 7

Q24. Chloroquine prevents detoxification of which molecule inside the parasite?

• Ferriprotoporphyrin IX (heme), preventing hemozoin formation
• Glutathione, preventing redox balance
• ATP, preventing energy production
• DNA, preventing replication

Correct Answer: Ferriprotoporphyrin IX (heme), preventing hemozoin formation

Q25. Regarding stereochemistry, chloroquine is considered:

• Achiral (no stereocenters)
• A racemic mixture of enantiomers
• A single R‑enantiomer only used clinically
• A diastereomeric mixture

Correct Answer: Achiral (no stereocenters)

Q26. In the nucleophilic substitution step of chloroquine synthesis, the leaving group on the quinoline intermediate is usually:

• Chloride
• Bromide
• Nitro group
• Hydroxyl group without activation

Correct Answer: Chloride

Q27. Detection of which specific point mutation is frequently used as a molecular marker for chloroquine resistance surveillance?

• K76T in pfcrt
• S108N in dhfr
• C580Y in pfk13
• G119S in ace‑1

Correct Answer: K76T in pfcrt

Q28. Co‑administration of which drug can increase chloroquine plasma concentrations by inhibiting its metabolism?

• Cimetidine (CYP inhibitor)
• Rifampicin (CYP inducer)
• St. John’s wort (CYP inducer)
• Antacids containing magnesium (no CYP effect)

Correct Answer: Cimetidine (CYP inhibitor)

Q29. The accumulation of chloroquine in acidic compartments is primarily due to which phenomenon?

• pH‑dependent ion trapping of the basic side chain
• Covalent binding to membrane lipids
• Active transport by human P‑glycoprotein into vacuoles
• Formation of insoluble chloroquine crystals

Correct Answer: pH‑dependent ion trapping of the basic side chain

Q30. For pregnant women exposed to chloroquine‑sensitive Plasmodium falciparum, current guidance generally states that chloroquine is:

• Considered safe for use in pregnancy when indicated
• Absolutely contraindicated in all trimesters
• Only safe during the first trimester
• Recommended at double adult doses during pregnancy

Correct Answer: Considered safe for use in pregnancy when indicated

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