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 investigating a medicinal plant observes that an extract
consistently produces a measurable physiological effect in an
experimental system. What is the most appropriate next step in a
traditional natural-product drug-discovery pathway?
A. Immediately begin Phase III clinical testing
B. Isolate and characterize the biologically active constituent(s)
,C. Replace the extract with a randomly selected synthetic compound
D. Perform computer docking before identifying the active constituent
Correct Answer:
B. Isolate and characterize the biologically active constituent(s)
Rationale:
B is correct because biologically active natural products can serve as
starting points for identifying chemical entities that can subsequently be
characterized, optimized, and developed as drug candidates. The
discovery pathway described in Chapter 1 traces the historical
importance of medicinal plants and natural products in identifying
pharmacologically active compounds.
A is incorrect because clinical trials require a sufficiently characterized
candidate and substantial prior preclinical development.
C is incorrect because replacing the extract randomly discards
potentially valuable information about the active constituent.
D is incorrect because computational methods generally become more
useful after a plausible compound or molecular target has been
identified.
Question 2
Why can a compound identified from a natural product be particularly
valuable during early drug discovery?
A. Its natural origin guarantees clinical safety
B. It provides a chemically defined starting point for further
optimization
, C. Natural compounds do not require toxicity testing
D. Natural compounds are automatically selective for one target
Correct Answer:
B. It provides a chemically defined starting point for further
optimization
Rationale:
B is correct because an active natural-product constituent can serve as
a starting chemical scaffold that medicinal chemists can modify to
improve potency, selectivity, pharmacological properties, and drug-like
characteristics.
A is incorrect because natural origin does not guarantee safety. A
naturally occurring compound can still have substantial toxicity.
C is incorrect because toxicity and safety evaluation remain necessary
regardless of the compound's source.
D is incorrect because natural products can interact with multiple
molecular targets and pathways.
Question 3
A pharmaceutical scientist describes two compounds as having different
potencies but similar maximal biological effects. Which statement best
explains this observation?
A. The compounds necessarily have different therapeutic mechanisms
B. The more potent compound produces the same maximal effect at a
lower concentration
C. The less potent compound must have greater toxicity
D. Potency determines whether a compound can be patented