Design, Synthesis, and Biological Evaluation of Novel C5-Modified Pyrimidine Ribofuranonucleosides as Potential Antitumor or/and Antiviral Agents
Background: Nucleoside analogues are well-known antitumor, antiviral, and chemotherapeutic
agents. Alterations on both their sugar and the heterocyclic parts may lead to significant
changes in the spectrum of their biological activity and the degree of selective toxicity, as
well as in their physicochemical properties.
Method: C5-arylalkynyl-β-D-ribofuranonucleosides 3-6, 3΄-deoxy 12-15, 3΄-deoxy-3΄-C-methyl-
β-D-ribofurananucleosides 18-21 and 2΄-deoxy-β-D-ribofuranonucleosides 23-26 of uracil, were
synthesized using a one-step Sonogashira reaction under microwave irradiation and subsequent
Results: All newly synthesized nucleosides were tested for their antitumor or antiviral activity.
Moderate cytostatic activity against cervix carcinoma (HeLa), murine leukemia (L1210) and human
lymphocyte (CEM) tumor cell lines was displayed by the protected 3΄-deoxy derivatives 12b,
12c, 12d, and the 3΄-deoxy-3΄-methyl 18a, 18b, 18c. The antiviral evaluation revealed appreciable
activity against Coxsackie virus B4, Respiratory syncytial virus, Yellow Fever Virus and Human
Coronavirus (229E) for the 3΄-deoxy compounds 12b, 14, and the 3΄-deoxy-3΄-methyl 18a, 18c,
18d, accompanied by low cytotoxicity.
Conclusion: This report describes the total and facile synthesis of modified furanononucleosides
of uracil, with alterations on both the sugar and the heterocyclic portions. Compounds 12b, 14 and
18a,c,d showed noticeable antiviral activity against a series of RNA viruses and merit further biological
and structural optimization investigations.
Journal Title: Medicinal Chemistry