2'-Deoxy-2'-fluorocytidine
[CAS# 10212-20-1]

Identification

• Classification: Biochemical >> Nucleoside drugs >> Deoxynucleotides and their analogues
• Name: 2'-Deoxy-2'-fluorocytidine
• Synonyms: 4-Amino-1-[(2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one; 2'-FdC
• Molecular Formula: C₉H₁₂FN₃O₄
• Molecular Weight: 245.21
• CAS Registry Number: 10212-20-1
• SMILES: C1=CN(C(=O)N=C1N)[C@H]2[C@@H]([C@@H]([C@H](O2)CO)O)F

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P305+P351+P338

Discovery and Applications

2'-Deoxy-2'-fluorocytidine is a synthetic nucleoside analogue chemically related to cytidine in which a fluorine atom replaces the hydroxyl group at the 2' position of the sugar moiety. This modification significantly alters its biological properties, enhancing its potential as a therapeutic agent.

The development of 2'-deoxy-2'-fluorocytidine stems from the desire to create nucleoside analogues with improved pharmacological characteristics. Researchers sought to modify the sugar component of nucleosides to enhance their stability and resistance to enzymatic degradation. Fluorine is similar in size to hydrogen but has a strong electronegativity and was introduced to impart this property. The synthesis of 2'-deoxy-2'-fluorocytidine involves complex organic chemistry techniques to precisely incorporate the fluorine atom.

The incorporation of fluorine into the nucleoside structure makes 2'-deoxy-2'-fluorocytidine a potent inhibitor of DNA synthesis. It mimics the natural nucleoside cytidine, but once incorporated into DNA, it disrupts the elongation process, leading to chain termination. This mechanism makes it particularly effective against rapidly proliferating cells, such as cancer cells and viruses.

2'-Deoxy-2'-fluorocytidine has shown promising results in the treatment of various cancers. It is used as a chemotherapeutic agent, particularly in hematological malignancies such as leukemias and lymphomas. Its ability to selectively target rapidly dividing cells while sparing normal cells makes it an attractive option in oncology.

The compound has shown antiviral activity against a variety of viruses, including HIV. By inhibiting viral DNA synthesis, 2'-deoxy-2'-fluorocytidine can inhibit viral replication, providing a potential therapeutic strategy for viral infections.

In molecular biology, 2'-deoxy-2'-fluorocytidine is used as a tool to study the mechanisms of DNA replication and repair. Its unique properties allow researchers to explore the intricate details of nucleic acid metabolism and the effects of nucleoside analogs on cellular processes.

The main advantage of 2'-deoxy-2'-fluorocytidine is its enhanced stability and resistance to degradation by nucleosidases. This stability means that activity in the body is prolonged, reducing the frequency of dosing required for therapeutic effects. In addition, the selective toxicity to cancer cells reduces the side effects commonly associated with chemotherapy.

Despite its benefits, the use of 2'-deoxy-2'-fluorocytidine is not without its challenges. Drug resistance may develop through mechanisms such as increased drug efflux or enhanced DNA repair, especially in cancer cells. Furthermore, precise dosing requires careful clinical management in order to maximize therapeutic effects while minimizing toxicity.

References

2022. Different Mechanisms of DNA Radiosensitization by 8-Bromoadenosine and 2′-Deoxy-2′-fluorocytidine Observed on DNA Origami Nanoframe Supports. The Journal of Physical Chemistry Letters, 13(16), 3767-3773.
DOI: 10.1021/acs.jpclett.2c00584

2023. 2- and 3-Fluoro-3-deaza-1′,6′-isoneplanocin: Synthesis and antiviral properties (including Ebola and Marburg). Bioorganic & Medicinal Chemistry Letters, 83, 129219.
DOI: 10.1016/j.bmcl.2023.129219

2021. Comparison of Antiviral Activity of Gemcitabine with 2′-Fluoro-2′-Deoxycytidine and Combination Therapy with Remdesivir against SARS-CoV-2. International Journal of Molecular Sciences, 22(4), 1581.
DOI: 10.3390/ijms22041581