2020 CHE3MBC Medicinal and Bioinorganic Chemistry - Tutorial Sheet 2 (Weeks 4-5)
Circle the letter (a), (b), (c) or (d) of the correct answer for each of the following multiple choice
questions. There is only one correct answer for each question.
2018 Question 1
(vi) Which of the following statements is the premise upon which the understanding of structureactivity relationships is based?
(a) Lead compounds are used as a starting point for further drug development
(b) Drugs work by forming intermolecular bonds with macromolecules
(c) Induced fit changes macromolecular activity
(d) Similar drugs have similar activities
(vii) Which of the following CANNOT be described by a pharmacophore?
(a) Atoms and functional groups which are important for binding
(b) The relative positions of atoms and functional groups in space
(c) The overall contribution to binding made by the compound skeleton
(d) The active conformation of a flexible molecule which binds to the target
(viii) Which compound substituent is least likely to bind to a hydrophobic pocket of the
biomolecular target?
(a) t-Butyl
(b) Aryl halide
(c) Alcohol
(d) Phenyl
(ix) What term describes the study of how a drug reaches its’ target binding site?
(a) Pharmacokinetics
(b) Pharmacodynamics
(c) Pharmacology
(d) Pharmacy
(x)
What is the following addition of an alkene called when optimising pharmacodynamics?
(a)
(b)
(c)
(d)
Extension
Rigidification
Expansion of a chain
Conformational blocker
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2019 Question 1
What factor determines how easily a natural product can be isolated from a plant extract?
(a)
Quantity
(b)
Structure
(c)
Stability
(d)
All of the above
Which of the following terms is important in quantitative structure activity relationship studies?
(a)
Pharmacophore
(b)
3D Pharmacophore
(c)
QSAR Pharmacophore
(d)
3D Bonding Type Pharmacophore
When attempting optimisation of the pharmacodynamic properties of a compound, which of the following
is likely to be an initial replacement for a methyl group?
(a)
ethyl
(b)
chlorine
(c)
aromatic ring
(d)
carboxylic acid
What is a chemical group called which has equivalent biological activity to another chemical group?
(a)
Biomolecule
(b)
Bioisostere
(c)
Enantiomer
(d)
Bioactive principle
Which of the following best describes the structure-activity relationships (SAR) of a drug?
(a)
The study of which structural features of the drug are important to metabolic activity
(b)
The study of which structural features of the drug are important to biological activity
(c)
The study of which structural features of the drug are important to chemical activity
(d)
The study of which structural features of the drug are important to chemical stability
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2019 Question 3
[6 + 1 + 3 = 10 marks]
Structure A (shown below) was a compound found to bind to and inhibit the angiotensin II enzyme
and was used in the design of the antihypertensive drug Losartan.
(i)
There are numerous optimisation strategies that could be used to improve the
pharmacodynamics of Structure A. Draw a structure that has been changed by the following
three strategies (i) variation of aryl substituents, (ii) extension and (iii) rigidification.
(ii)
How could the changes to Structure A proposed above result in improved
pharmacodynamics?
(iii)
Draw an isostere for each of the following functional groups of Structure A:
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2018 Question 3
[2 + 6 + 2 = 10 marks]
Staurosporine (shown below) is a potent kinase inhibitor and is a useful lead compound for
designing potential anticancer agents.
H
N
N
N
H3 C
O
O
H3CO
NHCH3
(i)
Determining structure-activity relationships of a compound is essential for understanding
the pharmacophore of a lead compound. For each of the bonding interactions listed below,
circle and label (on the structure above) a functional group of staurosporine that may be able
to undertake that type of bonding interaction with the kinase target.
(a)
(b)
(c)
(d)
Dipole-dipole interaction
Van der Waals (hydrophobic) interaction
Hydrogen bonding
Ionic interaction
(ii) There are a number of strategies available to improve the pharmacodynamics of staurosporine
during the drug design process. Draw an analogue of staurosporine that incorporates all of the
following optimisation strategies (in the space provided above) and outline the potential benefit
of undertaking each one (below).
(a) Variation of aryl substituent
(b) Expansion of ring
(c) Simplification
(iii) Another valuable strategy for optimising the pharmacodydnamics of a lead compound with the
target is to use bioisosteres. What is a bioisostere?
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2017 Question 3
[5 + 2 + 3 = 10 marks]
Structure I (shown below) was a compound found to bind to and inhibit the neuraminidase enzyme
of influenza and was used in the design of the drug Tamiflu.
(i)
Circle five different functional groups of Structure I and indicate what types of bonding
interactions each of them may be making with the binding site of the target.
(ii)
How would you go about identifying the pharmacophore of Structure I?
(iii)
Draw an analogue of Structure I with each of the following optimisation strategies applied:
(a) Variation of an alkyl substituent
(b) Ring variation
(c) Isostere or bioisostere
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