Cytosine β-D-arabinofuranoside

Cytosine β-D-arabinofuranoside

Cytarabine, also known as cytosine β-D-arabinofuranoside (Ara-C), is a nucleoside analog and antimetabolite chemotherapy drug. It is a cornerstone in the treatment of acute leukemias and certain lymphomas, functioning by disrupting DNA synthesis in rapidly dividing cancer cells.

Chemical Properties

• CAS Number: 147-94-4
• MDL No.: MFCD00066487
• Catalog Number: A808710
• EINECS: 205-705-9
• Molecular Formula: C₉H₁₃N₃O₅
• Molecular Weight: 243.22 g/mol
• Boiling Point: 386.09 °C
• Melting Point: 214 °C (lit.)
• Flash Point: 283.8 °C
• Appearance: White crystalline powder
• Optical Rotation: D²⁴ +153° (c = 0.5 in water)
• Refractivity: 1.5100
• Storage: Store at 2–8 °C for long-term stability (months).

Applications

1. Oncology:
   • Acute Myeloid Leukemia (AML): Primary use in induction and consolidation therapy, often combined with anthracyclines (e.g., daunorubicin).
   • Acute Lymphocytic Leukemia (ALL): Integral to treatment protocols for pediatric and adult ALL.
   • Lymphomas: Used in blast-phase chronic myelocytic leukemia and certain non-Hodgkin lymphomas.
2. Antiviral Activity:
   • Limited use in generalized herpesvirus infections due to severe bone marrow suppression and toxicity.
3. Neurological Research:
   • Controls glial cell proliferation in cultures and promotes neuronal differentiation in motor neuron-like cell lines.

Mechanism of Action

• Antimetabolite: Mimics cytidine but substitutes arabinose for deoxyribose, leading to incorporation into DNA during the S phase.
• DNA Synthesis Inhibition:
  • Converted intracellularly to cytarabine triphosphate (Ara-CTP), which competitively inhibits DNA polymerase α and β.
  • Causes chain termination and defective DNA repair, selectively targeting rapidly dividing cells.
• RNA and Enzyme Interference: Inhibits RNA polymerases and ribonucleotide reductase, further blocking DNA synthesis.

Administration

• Intravenous (IV): Most common route, via central line, PICC line, or cannula.
• Subcutaneous (SC): For specific protocols, injected into the stomach, thigh, or arm.
• Intrathecal (IT): Directly into cerebrospinal fluid for meningeal leukemia prophylaxis or treatment.

Safety Profile

• Common Side Effects:
  • Hematologic: Severe myelosuppression (neutropenia, thrombocytopenia, anemia).
  • Gastrointestinal: Nausea, vomiting, mucositis, diarrhea.
  • Neurologic: Cerebellar toxicity (ataxia, slurred speech) at high doses.
• Severe Toxicities:
  • High-Dose Risks: Neurotoxicity (cerebellar dysfunction, seizures), pulmonary edema, corneal toxicity.
  • Rare Complications: Pancreatitis, hepatic dysfunction, palmar-plantar erythrodysesthesia.

Clinical Considerations

• Dose Dependency:
  • Standard Dose: 100–200 mg/m² (induction therapy).
  • High-Dose (HDAC): 1,000–3,000 mg/m² for refractory/relapsed AML, requiring strict neurotoxicity monitoring.
• Combination Therapy: Synergizes with anthracyclines, fludarabine, and asparaginase3.

Citations:

1. https://en.wikipedia.org/wiki/Cytarabine
2. https://pubmed.ncbi.nlm.nih.gov/2031974/
3. https://pubmed.ncbi.nlm.nih.gov/9218105/
4. https://go.drugbank.com/drugs/DB00987
5. https://www.cancerresearchuk.org/about-cancer/treatment/drugs/cytarabine
6. https://www.tandfonline.com/doi/abs/10.3109/03639048909062750
7. https://ontosight.ai/glossary/term/Arabinoside—ara-C