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Griffith University 3025PHM Chemical Pharmacology II Semester 2, 2010

Workshop, Week 13 – Antivirals, Anti-influenza and Anticancer agents

1. Compare the structural differences between Relenza, the sialidase natural substrate (a
sialic acid containing glycoconjugate), and the transition state of sialic acid hydrolysis from a
carbohydrate chain by a sialidase. Use these structures to explain the mechanism of action
of Relenza.
H OH
H OH O CO2H
H OH HO CO2H
H OH CO2H O
O HO
HO O CO2H R
HO R
R HO H HN
R HO H HN
HO HO
H H OHOH NHNH
"transition state"
"transition state" H2HN2N
relenza
relenza

H OH CO2H
HO O
O O
R O glycoconjugate
HO H OH
natural substrate
Influenza virus neuraminidase

H OH OH
H OH
O CO2H HO
HO O CO2H
R
R HO H
HO H OH
OH
H2O R = NHAc
sialic acid
Griffith University 3025PHM Chemical Pharmacology II Semester 2, 2010

2. List the three major strategies for current antiviral therapies, explaining why they are
effective and give one example for each.

3. Using diagrams to assist your discussion, explain how nitrogen mustards, such as
mechlorethamine, are effective in the treatment of cancer.

Me

N
Cl Cl
mechlorethamine

Cl H2N
CO2H
N

Cl melphalan
("L-phenylalanine mustard")

Cl
O O
N P
HN
Cl
cyclophosphamide {OH}
Griffith University 3025PHM Chemical Pharmacology II Semester 2, 2010
4. Taxol can be used as an anticancer agent because:

a) It inhibits angiogenesis, therefore decreasing blood flow to, and slowing growth of, a
metastatic tumor
b) It is an antimetabolite, there it inhibits the synthesis of DNA precursors
c) It prevents depolymerisation of microtubules, which results in preventing mitosis and
ultimately causes cell death
d) It intercalates into DNA, causing single- or double-stranded breaks of the DNA

5. Explain, with the aid of diagrams, how the antimetabolite 5-fluorouracil elicits its effect

as a treatment for cancer. How does this differ to the mechanism of action of

methotrexate, which is also considered to be an antimetabolite?

O
F
HN

O N
H