Introduction to medicinal chemistry MCQs With Answer

Introduction to medicinal chemistry MCQs With Answer provides B. Pharm students a focused, Student-friendly primer to core concepts in drug discovery and pharmaceutical chemistry. This introduction highlights essential topics such as drug design, structure–activity relationships (SAR), pharmacophores, ADME, pharmacokinetics, drug metabolism (CYP450), QSAR, prodrugs, bioisosteres, stereochemistry, and common heterocyclic scaffolds. Designed for quick revision and exam preparation, these medicinal chemistry MCQs help strengthen problem-solving, analytical thinking, and application of theoretical principles to real-world drug development. Each question is crafted to deepen understanding and reinforce key mechanisms, synthetic considerations, and toxicity issues. Now let’s test your knowledge with 50 MCQs on this topic.

Q1. Which parameter most directly predicts oral bioavailability according to Lipinski’s rule of five?

• Molecular weight less than 500 Da
• Number of stereocenters
• Presence of a charged quaternary ammonium
• Number of rotatable bonds over 15

Correct Answer: Molecular weight less than 500 Da

Q2. In SAR studies, which modification is described by replacing a hydrogen atom with a fluorine atom to alter metabolic stability?

• Prodrug approach
• Bioisosteric replacement
• Salt formation
• Polymer conjugation

Correct Answer: Bioisosteric replacement

Q3. Which functional group conversion is characteristic of a Phase II metabolic reaction?

• Hydroxylation by CYP450
• Glucuronidation
• Oxidative deamination
• Reductive cleavage of azo bond

Correct Answer: Glucuronidation

Q4. Which molecular property is most associated with passive diffusion across cell membranes?

• High polar surface area (>140 Ų)
• High lipophilicity (log P ~ 2–5)
• High aqueous solubility
• Multiple charged centers

Correct Answer: High lipophilicity (log P ~ 2–5)

Q5. What is the primary catalytic role of cytochrome P450 enzymes in drug metabolism?

• Conjugation with sulfate
• Phase II transferase activity
• Oxidation of xenobiotics
• Hydrolysis of esters by esterases

Correct Answer: Oxidation of xenobiotics

Q6. Which stereochemical concept explains why enantiomers can have different pharmacological effects?

• Tautomerism
• Chirality and receptor stereoselectivity
• Conjugation length
• Geometric isomerism (cis-trans)

Correct Answer: Chirality and receptor stereoselectivity

Q7. A prodrug is designed primarily to:

• Increase intrinsic activity at receptor
• Enhance solubility, permeability or stability and convert in vivo
• Directly inhibit metabolizing enzymes
• Serve as an antidote

Correct Answer: Enhance solubility, permeability or stability and convert in vivo

Q8. Which heterocycle is commonly found in many kinase inhibitors?

• Pyridine
• Imidazole
• Indole
• Pyrimidine

Correct Answer: Pyrimidine

Q9. In quantitative structure–activity relationship (QSAR), the descriptor “log P” correlates with which biological property?

• Metabolic half-life directly
• Lipophilicity and membrane permeability
• Enzyme binding kinetics
• Optical rotation

Correct Answer: Lipophilicity and membrane permeability

Q10. Which interaction is most important for a drug binding to a hydrophobic pocket of a receptor?

• Hydrogen bonding
• Electrostatic ionic bonding
• Hydrophobic van der Waals interactions
• Covalent bond formation

Correct Answer: Hydrophobic van der Waals interactions

Q11. Tautomerism is important in medicinal chemistry because it can affect:

• Only the melting point of a compound
• Ionization state, binding interactions and bioavailability
• Color of the drug formulation
• Exclusive enzymatic cleavage

Correct Answer: Ionization state, binding interactions and bioavailability

Q12. Which class of drugs typically targets G-protein-coupled receptors (GPCRs)?

• Monoclonal antibodies exclusively
• Many small-molecule agonists and antagonists
• Only nucleic acid drugs
• Nonselective alkylating agents

Correct Answer: Many small-molecule agonists and antagonists

Q13. A compound with a tertiary amine is most likely to be:

• Strongly acidic
• Basic and possibly protonated at physiological pH
• Nonpolar and uncharged
• Unstable in aqueous solution

Correct Answer: Basic and possibly protonated at physiological pH

Q14. Which descriptor indicates the polar surface area that can affect intestinal absorption?

• Molar refractivity
• Topological polar surface area (TPSA)
• Log S (solubility)
• Partition coefficient at pH 7.4

Correct Answer: Topological polar surface area (TPSA)

Q15. Which discovery approach uses 3D structure of a protein target to design inhibitors?

• Fragment-based screening without structure
• Structure-based drug design (SBDD)
• Random combinatorial chemistry without assays
• Classical ethnobotany only

Correct Answer: Structure-based drug design (SBDD)

Q16. Which of the following is a common Phase I metabolic reaction?

• Sulfation
• Methylation via transferase
• Hydroxylation by CYP450
• Glucuronide conjugation

Correct Answer: Hydroxylation by CYP450

Q17. Bioisosteres are used to:

• Increase molecular weight exclusively
• Replace functional groups to improve potency, reduce toxicity or alter PK
• Render molecules fluorescent
• Convert nonpolar drugs to peptides

Correct Answer: Replace functional groups to improve potency, reduce toxicity or alter PK

Q18. Which property is measured by pKa?

• Partitioning between octanol and water
• Acid dissociation constant indicating ionization tendency
• Rate of metabolism by CYP3A4
• Electronegativity of substituents

Correct Answer: Acid dissociation constant indicating ionization tendency

Q19. Which molecule is an example of a beta-lactam antibiotic core?

• Penam (four-membered lactam fused to a five-membered ring)
• Benzodiazepine
• Macrolide lactone
• Quinolone core

Correct Answer: Penam (four-membered lactam fused to a five-membered ring)

Q20. Which test is commonly used to predict mutagenicity of small molecules?

• ELISA assay
• Ames test using Salmonella typhimurium strains
• Western blot
• Chromatography retention time

Correct Answer: Ames test using Salmonella typhimurium strains

Q21. Which interaction often stabilizes drug–enzyme transition states and is exploited by transition-state inhibitors?

• Hydrophobic stacking only
• Electrostatic stabilization and hydrogen bonding to charged transition state
• Metal chelation exclusively
• Covalent irreversible bond formation only

Correct Answer: Electrostatic stabilization and hydrogen bonding to charged transition state

Q22. Which term describes a substituent that has similar electronic and steric properties to another but different atom composition?

• Isoster
• Enantiomer
• Tautomer
• Homolog

Correct Answer: Isoster

Q23. Which enzyme family is primarily responsible for oxidative N-dealkylation?

• UDP-glucuronosyltransferases
• CYP450 monooxygenases
• Sulfotransferases
• Alcohol dehydrogenases

Correct Answer: CYP450 monooxygenases

Q24. Which factor can increase the rate of renal excretion of a weak acid drug?

• Alkalinization of urine
• Acidification of urine
• Decreasing urine flow
• Binding to plasma proteins

Correct Answer: Alkalinization of urine

Q25. Which descriptor is used in QSAR to represent electronic effects of substituents?

• Taft or Hammett constants
• Van der Waals radius only
• Molecular weight alone
• Optical rotation

Correct Answer: Taft or Hammett constants

Q26. What is the major consequence of high plasma protein binding for a drug?

• Higher free fraction and faster clearance
• Lower free fraction and potentially longer half-life
• Immediate renal filtration regardless of size
• Increased blood–brain barrier penetration

Correct Answer: Lower free fraction and potentially longer half-life

Q27. Which chemical feature often increases water solubility of a compound?

• Addition of hydrophobic alkyl chains
• Introduction of ionizable polar groups like carboxylic acids or amines
• Removal of all heteroatoms
• Converting to a larger polycyclic aromatic system

Correct Answer: Introduction of ionizable polar groups like carboxylic acids or amines

Q28. Which assay type is typically used for high-throughput screening (HTS) to identify lead compounds?

• In vivo toxicity in rodents
• Automated biochemical or cell-based reporter assays
• Long-term clinical trials
• Single-sample NMR only

Correct Answer: Automated biochemical or cell-based reporter assays

Q29. Which property is least desirable for a central nervous system (CNS) active drug?

• Low polar surface area and moderate lipophilicity
• High P-glycoprotein (P-gp) efflux susceptibility
• Ability to cross the blood–brain barrier
• Low molecular weight

Correct Answer: High P-glycoprotein (P-gp) efflux susceptibility

Q30. Which reaction would you use to selectively protect an alcohol group during multi-step organic synthesis?

• Oxidation to aldehyde
• Silylation to form a silyl ether
• Hydrogenation
• Nitration

Correct Answer: Silylation to form a silyl ether

Q31. A drug that irreversibly inhibits an enzyme often does so by:

• Noncovalent reversible binding only
• Covalent modification of an active-site residue
• Altering pH in the blood
• Forming micelles

Correct Answer: Covalent modification of an active-site residue

Q32. Which heteroatom-containing aromatic ring is most electron-deficient and often found in H-bond acceptor roles?

• Benzene
• Pyridine
• Thiophene
• Furan

Correct Answer: Pyridine

Q33. Which is an example of a covalent warhead used in targeted covalent inhibitors?

• Alcohol
• Acrylamide
• Ether
• Alkane

Correct Answer: Acrylamide

Q34. Which parameter describes the time required for plasma drug concentration to decrease by half?

• Bioavailability
• Volume of distribution
• Plasma half-life (t1/2)
• Clearance only

Correct Answer: Plasma half-life (t1/2)

Q35. Which modification can reduce CYP450-mediated metabolism at a labile site?

• Introducing a hydrogen-bond donor at that site
• Replacing metabolically labile hydrogen with fluorine
• Increasing the number of rotatable bonds
• Converting to a larger peptide

Correct Answer: Replacing metabolically labile hydrogen with fluorine

Q36. Which statement about enantiomers is correct?

• They always have identical pharmacological profiles
• They can have different potency, metabolism and toxicity
• They cannot be separated by chiral chromatography
• They have different molecular formulas

Correct Answer: They can have different potency, metabolism and toxicity

Q37. Which scaffold is commonly used as a bioisostere for carboxylic acid in drug design to reduce clearance?

• Tetrazole
• Benzene ring
• Methyl ester
• Alkyl chloride

Correct Answer: Tetrazole

Q38. Which technique provides detailed information on the 3D arrangement of atoms in a protein–ligand complex?

• UV–Vis spectroscopy
• X-ray crystallography
• Partition coefficient measurement
• Mass spectrometry alone

Correct Answer: X-ray crystallography

Q39. Which factor commonly causes drug–drug interactions via inhibition of metabolism?

• Induction of UDP-glucuronosyltransferase
• CYP450 enzyme inhibition by one drug affecting another’s clearance
• Increased renal filtration due to diuretics only
• Enhanced protein binding leading to decreased free drug

Correct Answer: CYP450 enzyme inhibition by one drug affecting another’s clearance

Q40. Which molecular property generally reduces penetration across the blood–brain barrier?

• Low molecular weight
• High polar surface area (>90–100 Ų)
• Moderate lipophilicity
• Lack of P-gp efflux recognition

Correct Answer: High polar surface area (>90–100 Ų)

Q41. Which reaction is typically catalyzed by esterases in vivo?

• Oxidative N-dealkylation
• Hydrolysis of esters to acids and alcohols
• Methyl transfer to thiols
• Conjugation with glucuronic acid

Correct Answer: Hydrolysis of esters to acids and alcohols

Q42. Which physicochemical change is most useful to reduce bitter taste and improve patient compliance?

• Increase lipophilicity drastically
• Mask taste by prodrug formation or formulation strategies
• Convert to a volatile compound
• Increase gastric irritation

Correct Answer: Mask taste by prodrug formation or formulation strategies

Q43. Which descriptor helps predict whether a compound will be a P-glycoprotein substrate?

• High TPSA and polar surface features combined with amphipathicity
• Low molecular weight alone
• High aromaticity with no polar atoms
• Pure hydrocarbon chains only

Correct Answer: High TPSA and polar surface features combined with amphipathicity

Q44. Which strategy is used to improve selectivity of a lead compound for a specific receptor subtype?

• Removing all polar groups randomly
• Structure–activity optimization focusing on unique interactions with the subtype binding pocket
• Increasing overall lipophilicity indiscriminately
• Decreasing molecular size until inactive

Correct Answer: Structure–activity optimization focusing on unique interactions with the subtype binding pocket

Q45. Which class of compounds often acts as reversible competitive enzyme inhibitors?

• Substrate analogs that mimic transition state poorly
• Compounds that closely resemble the natural substrate
• Irreversible alkylating agents exclusively
• Large insoluble polymers

Correct Answer: Compounds that closely resemble the natural substrate

Q46. Which safety concern is primarily assessed by measuring hERG channel inhibition?

• Renal clearance
• Potential for QT interval prolongation and cardiotoxicity
• Hepatotoxicity only
• Dermal irritation

Correct Answer: Potential for QT interval prolongation and cardiotoxicity

Q47. Which molecular property is increased when a drug forms a salt with a strong acid or base?

• Hydrophobicity
• Aqueous solubility
• Vapor pressure
• Number of chiral centers

Correct Answer: Aqueous solubility

Q48. Which pathway commonly deactivates aromatic amines via conjugation?

• Oxidation to alcohols only
• N-acetylation by N-acetyltransferases (NATs)
• Direct photolysis
• Glycosylation

Correct Answer: N-acetylation by N-acetyltransferases (NATs)

Q49. Which term describes design that minimizes off-target toxicity while retaining activity?

• Pharmacokinetics (PK) only
• Lead optimization for selectivity and safety
• Random screening expansion
• Formulation development exclusively

Correct Answer: Lead optimization for selectivity and safety

Q50. Which strategy helps in reducing first-pass metabolism for an orally administered drug?

• Designing a compound with high hepatic extraction ratio
• Using prodrugs, alternative routes or structural modifications to reduce hepatic metabolism
• Increasing lipophilicity to extreme values only
• Never considering intestinal absorption

Correct Answer: Using prodrugs, alternative routes or structural modifications to reduce hepatic metabolism

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