Alkylating agents

The oldest anti-cancer cytotoxic-alkylating agents—are antineoplastic drugs because they bind covalently via alkyl groups to DNA. They are divided into two groups:

♦ Unifunctional—with one reactive group.

♦ Bifunctional—with two reactive groups (more efficient at forming DNA cross-links).

Covalent binding to DNA occurs through the formation of a reactive aziridinium group.

The most common sites of alkylation are the N7 and O6 positions of guanine. Following cross-linking there is thought to be an arrest in G1-S transition followed either by DNA repair or apoptosis.

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