Goodman and Gilman's The
Pharmacological Basis of Therapeutics
14th Edition
Author(s)Laurence Brunton; Bjorn Knollmann
Print ISBN: 9781264258079
,Question 1
A research team begins investigating a plant traditionally used to relieve
severe pain. What is the most appropriate initial pharmacological
strategy for identifying a potentially active compound?
A. Determine the compound's oral bioavailability before testing its
biological activity
B. Use a biologically relevant assay to guide isolation of active
,constituents
C. Perform computer docking studies before obtaining a plant extract
D. Modify every constituent chemically before evaluating activity
Correct Answer:
B. Use a biologically relevant assay to guide isolation of active
constituents
Rationale:
A biologically guided approach allows investigators to determine
whether an extract has the desired activity and then follow that activity
during fractionation and purification. This strategy connects the
biological effect to specific chemical constituents.
• A is incorrect: Bioavailability cannot be meaningfully characterized
before identifying a candidate compound suitable for
pharmacokinetic study.
• C is incorrect: Docking generally requires a defined molecular
target and chemical structure; an undefined crude extract is not
an appropriate starting point.
• D is incorrect: Chemical modification is usually considered after an
active molecule or lead has been identified.
Question 2
Which feature best explains why natural products have historically been
important starting points for drug discovery?
A. They are always safer than synthetic compounds
B. They contain only one pharmacologically active molecule
, C. They provide structurally diverse molecules that may interact with
biological targets
D. They eliminate the need for lead optimization
Correct Answer:
C. They provide structurally diverse molecules that may interact with
biological targets
Rationale:
Natural products provide chemically diverse scaffolds generated
through biological evolution, making them valuable sources of
molecules with biological activity.
• A is incorrect: Natural origin does not guarantee safety. Natural
products can produce substantial toxicity.
• B is incorrect: Plants and other natural sources commonly contain
numerous constituents.
• D is incorrect: Natural-product-derived compounds often require
optimization to improve potency, selectivity, pharmacokinetics, or
safety.
Question 3
A medicinal chemist makes a small structural change to a lead
compound and observes substantially greater receptor affinity. Which
stage of drug discovery does this activity most directly represent?
A. Lead optimization
B. Clinical validation