ATC Group: L01AA Nitrogen mustard analogues

Bendamustine is an alkylating antitumour agent with unique activity. The antineoplastic and cytocidal effect of bendamustine is based essentially on a cross-linking of DNA single and double strands by alkylation. As a result, DNA matrix functions and DNA synthesis and repair are impaired.

Chlorambucil is an aromatic nitrogen mustard derivative which acts as a bifunctional alkylating agent. In addition to interference with DNA replication, chlorambucil induces cellular apoptosis via the accumulation of cytosolic p53 and subsequent activation of an apoptosis promoter.

Chlormethine is a bifunctional alkylating agent that inhibits rapidly proliferating cells. It works by binding to DNA, crosslinking two strands and preventing cell duplication. It binds to the N7 nitrogen on the DNA base guanine. It has been derivatized into the estrogen analogue estramustine phosphate, used to treat prostate cancer.

Cyclophosphamide has been demonstrated to have a cytostatic effect in many tumour types. The active metabolites of cyclophosphamide are alkylating agents which transfer alkyl groups to DNA during the process of cell division, thus preventing normal synthesis of DNA.

Ifosfamide is an antineoplastic, a cytotoxic alkylating agent. It is a prodrug and shows no in vitro cytotoxic activity until activated by microsomal enzymes. The cytotoxic activity of ifosfamide (alkylation of the nucleophilic centres in the cells) is associated with the activated oxazaphosphorine ring hydroxylated at the C4 atom which interacts with DNA-DNA cross linking. This activity manifests itself by blocking the late S and early G2 phases of the cell cycle.

Melphalan is a bifunctional alkylating agent. Formation of carbonium intermediates from each of the two bis-2-chloroethyl groups enables alkylation through covalent binding with the 7-nitrogen of guanine on DNA, cross-linking the two DNA strands and thereby preventing cell replication.