Structure of Mercaptopurine
Mercaptopurine, also known as 6-mercaptopurine (6-MP), is a purine analog with the following structural features:
Purine Base: Similar to hypoxanthine.
Thio Group: Contains a sulfur atom replacing the oxygen at position 6.
Chemical Formula: C₅H₄N₄O S
Structure of Mercaptopurine
Mode of Action
Mercaptopurine functions as an antimetabolite and purine antagonist by:
Incorporation into DNA and RNA: Disrupts nucleic acid synthesis and function.
Inhibition of Purine Synthesis Enzymes: Blocks enzymes like amidophosphoribosyltransferase, reducing purine nucleotide synthesis.
Induction of Apoptosis: Causes cytotoxicity in rapidly dividing cells, particularly in leukemic cells
Uses
Acute Lymphoblastic Leukemia (ALL): As part of combination chemotherapy regimens.
Chronic Myeloid Leukemia (CML): In certain treatment protocols.
Inflammatory Bowel Disease (IBD): Such as Crohn's disease and ulcerative colitis (off-label).
Autoimmune Disorders: Including rheumatoid arthritis (off-label).
Structure-Activity Relationship (SAR)
Purine Analog: The structural similarity to purine bases allows incorporation into DNA/RNA, disrupting nucleic acid function.
Thio Group at Position 6: Enhances binding to target enzymes and incorporation into nucleic acids, increasing cytotoxicity.
Substitution Patterns: Modifications on the purine ring can affect binding affinity and selectivity for target enzymes.
Synthesis
Mercaptopurine can be synthesized through the following steps:
Starting Material: Hypoxanthine.
Thiocyanation: Introduction of the thio group at position 6 using reagents like thiourea or phosphorus pentasulfide.
Purification: Isolation of 6-mercaptopurine through crystallization and recrystallization processes.
Synthetic Route Overview:
Hypoxanthine → Thio-functionalization → Mercaptopurine