• Elena Welchinska National Medical University
  • Valeriia Vilchynska National Medical University
Keywords: 5-fluorouracil, halothane, sarcoma, toxicity, bis-derivative


The problem of how to treat malignant tumors and the search for effective low-toxic anticancer drugs are among the most important in modern medicine and other chemical and biological sciences, including pharmaceutical chemistry. The arsenal of anticancer drugs occupies a prominent position as medications related to heterocyclic systems (cancer of the digestive system and other areas). In this regard, further development towards new derivatives of purine and pyrimidine series are of significant scientific interest and justify the relevance, novelty, and scientific practical significance of this study. Synthesis of 5-fluorouracil bis-derivative was performed with a halogen-containing pharmacophore group to compose a molecule that was studied for its physical, chemical, and biological properties. Synthesis of 5-fluorouracil bis-derivative is a typical example of substitution reactions with a heteroatom of the uracil molecule (N1) as the second component in the reaction involving halothane, a known inhaled anesthetic. The reaction was carried out in a solvent system of benzene-dimethylformamide-diethyl ether, under conditions of phase transfer catalysis with dibenzo-18-crown-6 (DB 18C6) complex (alkaline medium), by heating (14 h), followed by purification, and drying of the products. The structure of the synthesized compound was confirmed by elemental analysis, infrared, and proton nuclear magnetic resonance (1H NMR) spectroscopy. By varying the reaction conditions, a synthesized compound of high purity was obtained with increased practical output of up to 50%. The toxicity and antitumor activity of the synthesized compound were investigated. The new substance, 5-fluorouracil bis-derivative, was found to have high antitumor activity, reducing the Sarcoma 180 tumor by 51.7% (activity criterion > 50%). This suggests the synthesized compound is suitable as a physiologically active treatment and its further study as a potential vehicle for anti-tumor treatment in patients is recommended.


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