Alkylating agent

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Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumour growth by cross-linking guanine nucleobases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. These drugs acts mainly nonspecifically, some of them requires conversion into active substances in vivo (e.g. cyclophosphamide).

In the Anatomical Therapeutic Chemical Classification System, they are classified under L01A.

Cyclophosphamide is one of the most potent immunosuppressive substances. In small dosages, it is very efficient in the therapy of systemic lupus erythematosus, autoimmune hemolytic anemias, Wegener's granulomatosis and other autoimmune diseases. High dosages cause pancytopenia and hemorrhagic cystitis.

Dialkylating agents can react with two different 7-N-guanine residues and if these are in different strands of DNA the result is cross-linkage of the DNA strands, which prevents uncoiling of the DNA double helix. If the two guanine residues are in the same strand the result is called limpet attachment of the drug molecule to the DNA. Monoalkylating agents can react only with one 7-N of guanine. Limpet attachment and monoalkylation do not prevent the separation of the two DNA stands of the double helix but do prevent vital DNA processing enzymes from accessing the DNA. The final result is inhibition of cell growth or stimulation of apoptosis, cell suicide.

Since cancer cells generally divide more rapidly than do healthy cells they are more sensitive to DNA damage, and alkylating agents are used clinically to treat a variety of tumours.

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