Sulphonamides

Question 1

What does folic acid synthesise?

Answer 1

Thymidine monophosphate as it is a cofactor for thymidylate synthase which converts deoxyuridine monophosphate to thymidine monophosphate through the addition of a methyl group

Question 2

T/F sulphonamides inhibit folic acid processing

Answer 2

False - they inhibit the biosynthesis

Question 3

MoA of sulphonamides

Answer 3

Inhibit folic acid synthesis hence nucleic acid synthesis

They are competitive antagonists of para-aminobenzoic acid (a substrate which binds to dihydropteroate synthase to produce folic acid)

Directly inhibits dihydropteroate synthase by acting as a false substrate to produce inactive folic acid

Question 4

How are sulphonamides only selective to bacterial cells?

Answer 4

They inhibit the biosynthesis of folic acid

Humans can’t synthesise folic acid directly, we can only get it from our diet so we don’t see any effect in human cells

Question 5

What functional groups are essential for sulphonamide activity?

Answer 5

Unsubstituted P-amino group
Sulphonamide with a secondary nitrogen
Aromatic ring must be para-substituted

Question 6

How can you enhance the biological activity of sulphonamides?

Answer 6

Change the R group to lower the pKa

Low pKa = more biologically active

Need an electron withdrawing group to lower the pKa

Strong acid and more lipophilic = faster absorption but slower excretion

Question 7

What is a sulphone?

Answer 7

They are active against dihydropteroate synthase and have a similar MoA to sulphonamides (inhibit folic acid synthesis)

Increasing charge density of sulphone oxygen = increased activity

Question 8

How is folic acid synthesised?

Answer 8

2-amino-4-hydroxy-6-methylpteridine + p-aminobezoic acid + glutamic acid —> folic acid

Dihydropterate synthase is the enzyme that cleaves the first 2 together