Antiviral and Cytostatic Evaluation of 5-(1-Halo-2-sulfonylvinyl)- and 5-(2-Furyl)uracil Nucleosides.

Abstract

Transition metal-catalyzed halosulfonylation of 5-ethynyl uracil nucleosides provided (E)-5-(1-chloro-2-tosylvinyl)uridines. Tetrabutylammonium fluoride-mediated direct CH arylation of 5-iodouracil nucleosides with furan or 2-heptylfuran gave 5-furyl-substituted nucleosides without the necessity of using the organometallic substrates. These two classes of 5-substituted uracil nucleosides as well their corresponding ester derivatives were tested against a broad range of DNA and RNA viruses and the human immunodeficiency virus (HIV). The 3',5'-di-O-acetyl-5-(E)-(1-chloro-2-tosylvinyl)-2'-deoxyuridine (24) inhibited the growth of L1210, CEM and HeLa cancer cells in the lower micromolar range. The (β-chloro)vinyl sulfone 24 and 5-(5-heptylfur-2-yl)-2'-deoxyuridine (10) displayed micromolar activity against varicella zoster virus (VZV). The 5-(5-heptylfur-2-yl) analog 10 and its 3',5'-di-O-acetyl-protected derivative showed similar activity against the cytomegalovirus (CMV). The 5-(fur-2-yl) derivatives of 2'-deoxyuridine and arabino-uridine inhibited the replication of herpes simplex virus (HSV) TK+ strains while the 5-(5-heptylfur-2-yl) derivative 10 displayed antiviral activity against the parainfluenza virus.

• Authors: Zhiwei Wen, Sazzad H Suzol, Jufang Peng, Yong Liang, Robert Snoeck, Graciela Andrei, Sandra Liekens, Stanislaw F Wnuk
• Journal: Archiv der Pharmazie (Arch Pharm (Weinheim)) Vol. 350 Issue 3-4 (Apr 2017) ISSN: 1521-4184 [Electronic] Germany
• PMID: 28304114 (Publication Type: Journal Article)
• Copyright: © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antiviral Agents
• Cytostatic Agents
• Nucleosides
• Uracil

Topics

• Animals
• Antiviral Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cytostatic Agents (chemical synthesis, chemistry, pharmacology)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Humans
• Mice
• Microbial Sensitivity Tests
• Molecular Structure
• Nucleosides (chemical synthesis, chemistry, pharmacology)
• Structure-Activity Relationship
• Uracil (analogs & derivatives, chemistry, pharmacology)
• Viruses (drug effects)