Mechanism of action of busulfan as an antineoplastic agent

 Busulfan 

Busulfan is an antineoplastic agent. It is a white crystalline powder. The molecular weight is 246.3gm/mol. It is insoluble in water and soluble in acetone. The melting point of busulfan is 237-244⁰c. It is also known as, Myleran, Busulphan, Sulphabutin, Busulfex, Citosulfan, Mielucin, Mablin, Mielevcin, Mifostan, Mielosan, Buzulfan, Myeleukon.

■ Structure:-

The moleculer formula of busulfan is,

                                                      [C6H14O6S2]

The IUPAC name is,  4-methylsulfonyloxybutyl methanesulfonate.

■ Synthesis:-

■ Mechanism of action:-

Busulfan is a bifunctional alkylating agent. It alkylates the DNA by forming carbonium ions, which results in the interference of DNA replication. It breakdown the guanine-adenine intrastrand cross-links. This cross-link occurs through an SN2 reaction guanine N7 nucleophilically attacks the carbon adjacent to the leaving group. This kind of damage cannot be repaired by cellular machinery and the cell undergoes apoptosis.

■ Uses:-

It is used in the treatment of,

• Chronic myelogenous leukemia.
• Brain Malignancy. 
• Stem cell transplantation.
• Hepatic impairment. 
• Renal impairment. 

■ Dosage:-

The usual adult dose of busulfan is, 60mg per kg per day or 1.8gm per meter square, intravenously.  The maintenance dose is 1-4mg/day to 2mg/week.

■Side-effects:-

The major Side-effects of busulfan are, 

• Nausea.
• Diarrhea. 
• Constipation. 
• Dry mouth.
• Loss of appetite. 
• Sores in mouth and throat.
• Headache. 
• Difficulty in falling asleep. 
• Anxiousness. 
• Chest, joint, muscle, and back pain.
• Skin rash.
• Itching.
• Hair loss.
• Darkened skin.

   ..........THE END..........