DNA-interactive anticancer agents - DNA-cleaving agents

Question 1

How do DNA-Cleaving agents work?

Answer 1

Bind to DNA helix in a sequence selective manner and cleave the helix through radical production

Question 2

example of DNA-cleaving agent and how it works

Answer 2

Bleomycin.

• Heterocyclic bithiazole moiety inserts between DNA pairs
• Second domain (β-hydroxyhistidine, β-aminoalanine and pyrimidine) forms an iron complex which interacts with O2 to give free radicals leading to strand breaks

Third domain (glycopeptidic): no direct antitumor activity but thought to contribute to drug uptake in tumor cells/ additional stabilization of H bond interactions.

• Side effects:
• Slight myelosuppression
• Dose limiting toxicity: skin, mucosa

Hypersensitivity immediately after: chills and fevers