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 with a medicinal plant that has been used
traditionally for relief of inflammatory symptoms. The investigators
want to determine which constituent is responsible for the biological
activity. Which approach is most appropriate as an early step in the
discovery process?
,A. Perform a large randomized clinical trial of the whole plant
B. Isolate constituents and link chemical fractions to measurable
biological activity
C. Submit the plant extract directly for regulatory approval
D. Use molecular docking before identifying any potentially active
constituents
Correct Answer: B
Rationale:
B is correct because natural-product discovery commonly begins by
connecting biological activity with specific chemical constituents
through extraction, fractionation, and bioassay-guided investigation.
This converts an empirically observed effect into a tractable chemical
lead. The chapter explicitly places early medicinal-plant experience
within the historical evolution of drug discovery.
A is incorrect because definitive clinical trials are not an appropriate
first step before the active substance, dose, safety, and pharmacologic
properties are characterized.
C is incorrect because regulatory approval requires substantial evidence
of quality, efficacy, and safety.
D is incorrect because computational modeling is most useful when a
plausible molecular target or chemical structure is available for analysis.
Question 2
A natural product demonstrates activity in a disease-relevant assay but
contains several chemically distinct compounds. Which development
problem must be solved before the researchers can rationally optimize
a lead compound?
, A. Determining which molecular component is responsible for the
observed activity
B. Establishing the final commercial price of the drug
C. Performing phase III clinical testing
D. Selecting a final dosage schedule for patients
Correct Answer: A
Rationale:
A is correct because a complex extract may contain multiple
constituents, and identifying the active component is necessary for
reproducible characterization and subsequent medicinal chemistry.
B is incorrect because pricing is not the scientific problem that
determines which constituent is pharmacologically active.
C is incorrect because phase III studies occur much later, after
substantial preclinical and clinical development.
D is incorrect because a definitive dosage schedule cannot be rationally
selected before the active drug candidate and its pharmacologic
properties are established.
Question 3
A compound discovered during screening produces the desired
biological effect but also interacts with several unrelated proteins. The
development team modifies its chemical structure while testing closely
related analogs. What is the primary purpose of this process?
A. To determine whether the compound can be patented without
further testing
B. To improve desirable properties while reducing liabilities associated