Drugs which interact with DNA

Question 2

What drugs inhibit nucleic acid synthesis (2)

Answer 2

1. Antimetabolites
2. Enzyme inhibitors

Question 3

What are examples of antimetabolites (3)

Answer 3

1. Anti-folates
2. Purine antimetabolites
3. Pyrimide antimetabolites

Question 4

What drugs target existing nucleic acids (3)

Answer 4

1. Intercalating agents
2. Alkylating agents
3. Chain-cleaving agents

Question 5

How do antimetabolites work (3)

Answer 5

1. Blocking normal metabolic pathways
2. Replacing an endogenous compound (compound already in that metabolic pathway) with another (or drug).
3. Inhibiting an enzyme in the metabolic pathway

Question 6

How do anti-folates work (4)

Answer 6

1. block the action of folate which is needed to synthesise purine for heterocyclic bases in nucleic acids
2. Normal pathway = Folic acid → tetrahydrofolate → purine
3. Antifolates interfere with this process, inhibiting DNA synthesis and preventing cell replication.
4. e.g. methotrexate

Question 7

How do purine antimetabolites work (4)

Answer 7

1. Stops fulfilling nucleic acid structure.
2. inhibiting several enzymes in purine biosynthesis.
3. e.g. 6-mercaptopurine
4. has crossover drug action - e.g. an antimetabolite that interferes with the enzymes in a metabolic process.

Question 8

How do pyrimidine antimetabolites work (6)

Answer 8

1. Work against normal pyrimidine processes
2. Takes the place of pyrimidine
3. Inhibits the conversion of uridine monophosphate (UMP) to other pyrimidine nucleotides
4. Action is due to the presence of Fluorine on carbon 5. Bonds with fluorine are very strong.
5. High selectivity for damaged cells.
6. e.g. 5-fluorouracil

Question 9

How do enzyme inhibitors work (4)

Answer 9

1. Inhibit enzymes in normal metabolic processes - slowing down the processes
2. Topoisomerases are enzymes responsible for the supercoiling, cleavage and rejoining of DNA. Inhibition prevents transcription – and has antitumour action.
3. Usually, inhibitors have complex structures.
4. Also toxic to the heart

Question 10

How do intercalating agents work (6)

Answer 10

1. Insert themselves into spaces between the bases of the DNA helix disrupting the shape and coils of the DNA helix.
2. Causes DNA helix to unwind partially – inhibits transcription.
3. Planar flat molecules nm in size
4. e.g. antimalarial quinine and chloroquine
5. e.g. anticancer agents mitoxantrone and doxorubicin
6. Mostly orally inactive needs to be administered intravenously
7. cardiotoxic side effects

Question 11

How do alkylating agents work (7)

Answer 11

1. Covalently bond to nucleic acid chains - nucleophilic substitution reaction
2. Frequently form intrastrand or interstrand cross-links – inhibit transcription.
3. Usually, they have severe side effects due to interaction with other biomolecules.
4. are usually electrophiles - e.g. nitrogen mustards such as Mustine.
5. They may also be pro-electrophiles - e.g. temozolomide.
6. nucleic acid is the nucleophile, and the drug is the electrophile.
7. Pro-drugs are not active when taken but become active after going through processes in the body.

Question 12

How do chain-cleaving agents work (3)

Answer 12

1. Results in breaking of nucleic acid into fragments
2. The exact mechanism of action is uncertain.
3. e.g. bleomycin