Mechlorethamine

Structure

• Chemical Structure of Mechlorethamine – C5H11Cl2N

Structure-Activity Relationship (SAR) of Meclorethamine

• Meclorethamine, also known as nitrogen mustard, is an alkylating agent used in chemotherapy.

• It's known for its ability to form covalent bonds with DNA, leading to cross-linking and ultimately cell death.

The SAR characteristics of meclorethamine are:

1. Bis(2-chloroethyl) Group:

• The presence of two 2-chloroethyl groups is essential for the alkylating activity.

• These groups are responsible for the formation of ethyleneimmonium ions, which are the active species that alkylate DNA.

2. Nitrogen Atom:

• The central nitrogen atom is crucial as it forms a positively charged aziridinium ion upon activation.

• This ion is highly reactive towards nucleophiles, such as DNA bases.

3. Alkyl Chain Length:

• The length of the alkyl chain affects the reactivity and cytotoxicity.

• In meclorethamine, the ethyl (two-carbon) chain is optimal for activity.

4. Lipophilicity:

• The overall lipophilicity of the molecule affects its ability to penetrate cell membranes.

• Meclorethamine has sufficient lipophilicity to effectively enter cells.
  

Synthesis of Mechlorethamine

The chemical synthesis of Mechlorethamine is relatively straightforward, involving a simple reaction:

1. Synthesis Reaction:

• 2(CH2​=CH2​) + HN(CH2​CH2​Cl)2​ → (CH2​CH2​Cl)2​NCH3 ​+ 2HCl 

• In this reaction, bis(2-chloroethyl) amine reacts with ethylene to form meclorethamine along with the production of hydrochloric acid.

• This reaction is a typical example of an alkylation, where an amine group is alkylated using an alkene in the presence of a strong acid.

• The simplicity of this reaction is one of the reasons why meclorethamine was one of the first chemotherapy agents to be widely used.

Mode of action

Alkylating substances function in three separate ways:

I.  When alkyl groups are attached to DNA bases, repair enzymes may fragment the DNA to replace the alkylated bases, which prevents DNA synthesis and RNA transcription from the damaged DNA.

II.  Cross-links (bonds between DNA atoms) that occur because of DNA damage hinder DNA from being separated for synthesis or transcription.

III. the production of incorrect nucleotide pairing, which results in mutations.

Uses

• This drug is applied to the skin to treat a specific kind of cancer.

• It functions by reducing or stopping the development of the cancerous cells that are the cause of the skin problem.

• Used in the treatment of Hodgkin’s disease.