Dihydropyrimidinone/1,2,3-triazole hybrid molecules: Synthesis and anti-varicella-zoster virus (VZV) evaluation

  • Eur J Med Chem. 2018 Jul 15:155:772-781. doi: 10.1016/j.ejmech.2018.06.028.
Hanane Kaoukabi  1 ,  Youssef Kabri  2 ,  Christophe Curti  2 ,  Moha Taourirte  3 ,  Juan C Rodriguez-Ubis  4 ,  Robert Snoeck  5 ,  Graciela Andrei  5 ,  Patrice Vanelle  6 ,  Hassan B Lazrek  7
Affiliations
  • 1. Laboratory of Bioorganic and Macromolecular Chemistry, Department of Chemistry, Faculty of Sciences and Technology, Gueliz (FSTG), Marrakesh, Morocco; Laboratory of Biomolecular and Medicinal Chemistry, Department of Chemistry, Faculty of Sciences Semlalia (FSSM), Marrakesh, Morocco.
  • 2. Aix Marseille University, Institut de Chimie Radicalaire ICR, UMR CNRS 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin-CS 30064, 13385, Marseille CEDEX 05, France.
  • 3. Laboratory of Bioorganic and Macromolecular Chemistry, Department of Chemistry, Faculty of Sciences and Technology, Gueliz (FSTG), Marrakesh, Morocco.
  • 4. Laboratory Organic-Inorganic Solids and Luminiscent Probes (M01-L207), Department of Organic Chemistry, Faculty of Sciences, University Autonoma, Madrid, Spain.
  • 5. Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
  • 6. Aix Marseille University, Institut de Chimie Radicalaire ICR, UMR CNRS 7273, Laboratoire de Pharmaco-Chimie Radicalaire, Faculté de Pharmacie, 27 Boulevard Jean Moulin-CS 30064, 13385, Marseille CEDEX 05, France. Electronic address: [email protected].
  • 7. Laboratory of Biomolecular and Medicinal Chemistry, Department of Chemistry, Faculty of Sciences Semlalia (FSSM), Marrakesh, Morocco. Electronic address: [email protected].
PMID: 29945100 DOI: 10.1016/j.ejmech.2018.06.028
Abstract

By combining the structural features of dihydropyrimidinone and 1,2,3-triazole heterocycles, novel hybrid compounds were synthesized using a simple and convenient method. A series of novel mono and bis 1,2,3-triazole was synthesized via copper-catalyzed Huisgen azide-alkyne cycloadditions (CuAAC) under microwave irradiation. The newly synthesized compounds were evaluated for their Antiviral activity against varicella-zoster virus (VZV). Compounds 6aa, 7ab, 6ba and 6da showed valuable Antiviral activities, with EC50 values ranging from 3.6 to 11.3 μM against TK+ and TK- VZV and without measurable cell-growth inhibition.

Keywords
1,2,3-Triazole; 1,3-Dipolar cycloaddition; Anti-VZV; Biginelli reaction; Hybrid molecules; Microwave.