Synthesis and biological evaluation of 2-oxonicotinonitriles and 2-oxonicotinonitrile based nucleoside analogues.
Drug resistance and emergence of new pathogens highlight the need for developing new therapeutic agents. We focused on 2-oxonicotinonitrile (2-ONN) as derivative of the natural product 2-pyridinone.(1) Herein, we describe the synthesis of 2-ONNs bearing two aryl groups, which we coupled with organohalides, including three glycosyl bromides, to prepare the nucleoside analogues. Coupling occurred mostly at the 2-ONN ring nitrogen to give the aimed targets, and in a few cases, it happened at the 2-oxo position giving O-alkylation products. Free 2-ONNs and their acetylated nucleosides were tested against a number of viruses. The nucleoside analogue 2a(Ac) showed good anti SARS-CoV and anti influenza A (H₅N₁) activities. Additionally, 7b had good activity against Gram positive bacterium, Bacillis subtilis.
Department of Chemistry, Faculty of Sciences, Zagazig University, Zagazig, Egypt. Electronic address: rabouelkhair@zu.edu.eg.
Reham A I
RA
Abou-Elkhair
Department of Chemistry, Faculty of Sciences, Zagazig University, Zagazig, Egypt. Electronic address: ah_hu_mostafa@yahoo.com.
Ahmed H
AH
Moustafa
Department of Chemistry, Faculty of Sciences, Zagazig University, Zagazig, Egypt.
Abdelfattah Z
AZ
Haikal
Department of Chemistry, Faculty of Sciences, Zagazig University, Zagazig, Egypt.
Ahmed M
AM
Ibraheem
D001419:Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology*; D014780:Viruses / Q000187:drug effects
D009570:Nitriles
2-Oxonicotinonitrile; 2-Pyridinone; Antimicrobial; Antiviral; Glycosylation; Nucleoside analogues