Busulfan | Alkylating Agent | CAS 55-98-1 | Antineoplastic

Product Name: Busulfan
CAS No.: 55-98-1
Chemical Name: 1,4-Butanediol dimethanesulfonate
Molecular Formula: C₆H₁₄O₆S₂
Appearance: White crystalline powder
Solubility: Practically insoluble in water; sparingly soluble in ethanol; soluble in acetone. Special formulations are used for intravenous administration.
Stability: Relatively stable when dry

1. Introduction

Busulfan is an alkylating antineoplastic agent, a bifunctional alkyl sulfonate. It exerts cytotoxic effects primarily on myeloid progenitor cells. It is used for the treatment of chronic myelogenous leukemia and in high doses for myeloablative therapy.

Busulfan was synthesized in the mid-20th century and became one of the first effective drugs for the treatment of chronic myelogenous leukemia (CML). Its mechanism of action involves the formation of crosslinks with DNA, leading to disruption of DNA function and cell death. At high doses, busulfan causes profound myelosuppression, which is used for conditioning (preparation) of patients prior to hematopoietic stem cell transplantation.

2. Chemical Structure & Synthesis

The busulfan molecule is an ester of 1,4-butanediol and two methanesulfonic acid residues.

Synthesis: Busulfan is obtained by reacting 1,4-butanediol with methanesulfonyl chloride in the presence of a base (e.g., pyridine) to bind the released hydrogen chloride.

3. Mechanism of Action

Busulfan is a bifunctional alkylating agent. After entering the cell, it undergoes hydrolysis with the elimination of methanesulfonate groups, forming electrophilic carbocation ions. These ions interact with nucleophilic centers in DNA (primarily at the N7 position of guanine), forming monoadducts and, more importantly, interstrand and intrastrand DNA crosslinks. This leads to disruption of DNA replication and transcription, induction of apoptosis, and cell death. Busulfan has relative selectivity for myeloid lineage cells.

4. Pharmacokinetics

Well absorbed after oral administration. Also available as an intravenous formulation, which provides more predictable pharmacokinetics. Metabolized in the liver, primarily by conjugation with glutathione. Excreted by the kidneys as metabolites.

5. Applications

• Treatment of chronic myelogenous leukemia (CML) – particularly in the chronic phase (historically the drug of choice; its role has diminished with the advent of tyrosine kinase inhibitors)

• Myeloablative therapy (conditioning) prior to hematopoietic stem cell (bone marrow) transplantation for the treatment of leukemias, lymphomas, multiple myeloma, and other hematologic and oncologic diseases – typically used at high doses, often in combination with other cytostatics (e.g., cyclophosphamide)

• Treatment of polycythemia vera and essential thrombocythemia – less commonly

• Treatment of myelofibrosis

6. Conclusion

Busulfan is a potent alkylating agent with pronounced myelosuppressive activity. It has played an important role in the treatment of chronic myelogenous leukemia and remains a key component of conditioning regimens prior to hematopoietic stem cell transplantation. The use of busulfan requires careful monitoring due to its narrow therapeutic index and risk of serious side effects, including profound myelosuppression, pulmonary toxicity (busulfan lung), and veno-occlusive disease of the liver.