These aim to inhibit reproduction of neoplastic cells adverse affects occur when they inhibit normal cells.
Most widely used agents. Highly reactive compounds.
Mechanism of action is by adding an alkyl group to DNA cell death.
eg Nitrogen mustards (cyclophosphamide, mechlorethamine, ifosfamide); nitrosoureas (carmustine, lomustine); cisplatin
Compete for binding sites on enzymes or incorporated into DNA or RNA
Methotrexate (folic acid analog):
• inhibits dihydrofolate reductase (enzyme that converts dihydrofolic acid into tetrahydrofolic acid – this is a necessary step in the activation of folic acid needed for synthesis of DNA, RNA and proteins)
• used in conjunction with leucovorin for some cancers to protect normal cells
• inhibit biosynthesis of pyrimidine, DNA and RNA
• eg cytarabine (becomes incorporated into DNA, suppressing further DNA synthesis); Fluorouracil (inhibits thymidylate synthetase)
• eg Mercaptopurine (disrupts purine synthesis)