Synthesis of Nucleosides and Non-nucleosides Based 4,6-disubstituted-2-oxo-dihydropyridine-3-carbonitriles as Antiviral Agents

Tarek S. Ibrahim, Hassan A. El-Sayed, Maan T. Khayat, Amany M.M. Al-Mahmoudy, Ahmed H. Moustafa, Ayat K.S. El-Deen, Sherif A.F. Rostom, Siva S. Panda

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

BACKGROUND: Viral diseases are considered main threats that face the humanity worldwide. The emergence of new viruses like influenza viruses emphasizes the significance of designing novel antiviral drugs. METHOD: The aim of this work is to synthesize a new set of nucleoside and non-nucleoside cyanopyridine, characterized and evaluated for their in vitro antiviral properties against various strains. CONCLUSION: More of the compounds showed variable antiviral potential against a panel of eighteen DNA and RNA viruses. The screening data suggested that the order of activity of the active compounds are in the order of O-glycosyl > O-alkyl > N-alkyl > S-alkyl derivatives. In addition, the 4-fluoro substituted compounds are more effective among the O- and N-alkyl analogs, whereas remarkable antiviral activity was ascribed to the methoxylated O-glycosyl derivatives. Most of the active compounds proved to be more selective towards the inhibition of the replication of DNA rather than the RNA-viruses. The analogs 1a, 2a, 12b, 14b and 16b possessed broad spectrum and noticeable antiviral potential against most of the tested DNA- and RNA-viruses (EC50 ≈ 0.8-20 µM), accompanied with considerably low cytotoxic margin (MCC ≈ 4-20 µM), and comparable with reference standard antiviral agents.

Original languageEnglish (US)
Pages (from-to)791-808
Number of pages18
JournalMedicinal chemistry (Shariqah (United Arab Emirates))
Volume14
Issue number8
DOIs
StatePublished - Jan 1 2018

Keywords

  • Synthesis
  • antiviral
  • influenza viruses
  • non-nucleosides
  • nucleosides
  • pyridine.

ASJC Scopus subject areas

  • Drug Discovery

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