2. Mechanism of Action
● An alkylating antineoplastic agent is an alkylating agent used in
cancer treatment that attaches an alkyl group (CnH2n+1) to DNA.
● The alkyl group is attached to the guanine base of DNA, at
the number 7 nitrogen atom of the purine ring.
● A bis(chloroethyl)amine forms an ethyleneimonium ion and a
carbonium ion that react with base (guanine) of DNA.
3.
4. Classical Alkylating agents
Nitrogen Mustards
● Cyclophosphamide — the most widely used alkylating
agent of modern times.
● Chlormethine also known as mechlorethamine or mustine (HN2) — the first
alkylating agent to receive regulatory approval.
5. SAR of Nitrogen Mustards
● Ethylene moiety between N and Cl is essential for the
activity to form aziridinium ion.
● Decrease and increase in the length of this moiety abolish
activity.
● Halogen other than Cl decrease the activity.
● Nitrogen mustard contains bis(2-chloroethyl) group.
Modification of this group change the stability, reactivity
and lipophilicity of the compound.
