MPharm Master of Pharmacy Medicinal Chemistry and Drug Design 1 — Questions and Answers
Question 1: What is the primary purpose of the Lipinski Rule of Five in drug design?
- Predict drug toxicity in animal models
- Predict oral bioavailability based on physicochemical properties (Correct answer)
- Determine drug-receptor binding affinity
- Estimate metabolic stability in the liver
Correct answer: Predict oral bioavailability based on physicochemical properties
Lipinski's Rule of Five predicts whether a drug candidate has physicochemical properties likely to result in good oral absorption and bioavailability.
Question 2: Which functional group is most commonly targeted by irreversible inhibitors to form a covalent bond with an enzyme?
- Amino group
- Carboxyl group
- Serine hydroxyl group (Correct answer)
- Methyl group
Correct answer: Serine hydroxyl group
Many irreversible inhibitors react with the serine hydroxyl in the enzyme's active site, as seen with aspirin's acetylation of COX-1 serine residue.
Question 3: In structure-activity relationship (SAR) studies, what does the bioisostere concept involve?
- Replacing a radioactive atom with a stable isotope
- Substituting a group with another of similar size and electronics to maintain activity (Correct answer)
- Adding a prodrug moiety to improve absorption
- Removing a chiral center to simplify synthesis
Correct answer: Substituting a group with another of similar size and electronics to maintain activity
Bioisosteric replacement substitutes one atom or group with another having similar steric and electronic properties to retain or improve biological activity.
Question 4: What is the pharmacophore of a drug?
- The drug's molecular formula
- The minimum structural features required for biological activity (Correct answer)
- The route by which a drug is administered
- The metabolic byproduct of a drug
Correct answer: The minimum structural features required for biological activity
A pharmacophore defines the essential 3D arrangement of atoms and functional groups needed for a drug to interact with its target and produce activity.
Question 5: Which technique is used in fragment-based drug discovery (FBDD) to detect weak fragment binding to a target protein?
- High-performance liquid chromatography (HPLC)
- Surface Plasmon Resonance (SPR) (Correct answer)
- Gas chromatography-mass spectrometry (GC-MS)
- Karl Fischer titration
Correct answer: Surface Plasmon Resonance (SPR)
SPR measures real-time binding events between a fragment and an immobilized target protein by detecting changes in refractive index.
Question 6: Prodrugs are designed primarily to address which drug property limitation?
- Poor receptor selectivity
- High protein binding
- Poor absorption or membrane permeability (Correct answer)
- Excessive plasma half-life
Correct answer: Poor absorption or membrane permeability
Prodrugs are inactive precursors converted in vivo to the active drug, improving absorption, permeability, or stability of the parent compound.
