title: 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.affiliation: Department of Chemistry and Biochemistry, Florida International University, Miami, FL, USA.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Department of Chemistry and Biochemistry, Florida International University, Miami, FL, USA.
authors.forename: Sazzad H
authors.initials: SH
authors.lastname: Suzol
authors.affiliation: Department of Chemistry and Biochemistry, Florida International University, Miami, FL, USA.
authors.forename: Jufang
authors.initials: J
authors.lastname: Peng
authors.affiliation: Department of Chemistry and Biochemistry, Florida International University, Miami, FL, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Snoeck
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Graciela
authors.initials: G
authors.lastname: Andrei
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Liekens
authors.affiliation: Department of Chemistry and Biochemistry, Florida International University, Miami, FL, USA.
authors.forename: Stanislaw F
authors.identifier: http://orcid.org/0000-0002-3111-3919
authors.initials: SF
authors.lastname: Wnuk
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D054697:Cytostatic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014498:Uracil / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D014780:Viruses / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D054697:Cytostatic Agents; D009705:Nucleosides; D014498:Uracil
keywords: Anticancer agents; Antiviral agents; Prodrugs; Pyrimidine nucleosides; Vinyl sulfones