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

Hanane Kaoukabi; Youssef Kabri; Christophe Curti; Moha Taourirte; Juan C Rodriguez-Ubis; Robert Snoeck; Graciela Andrei; Patrice Vanelle; Hassan B Lazrek

doi:10.1016/j.ejmech.2018.06.028

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. Epub 2018 Jun 13.

Authors

Hanane Kaoukabi¹, Youssef Kabri², Christophe Curti², Moha Taourirte³, Juan C Rodriguez-Ubis⁴, Robert Snoeck⁵, Graciela Andrei⁵, Patrice Vanelle⁶, Hassan B Lazrek⁷

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: patrice.vanelle@univ-amu.fr.
⁷ Laboratory of Biomolecular and Medicinal Chemistry, Department of Chemistry, Faculty of Sciences Semlalia (FSSM), Marrakesh, Morocco. Electronic address: hblazrek@uca.ac.ma.

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.

MeSH terms

Antiviral Agents / chemical synthesis
Antiviral Agents / chemistry
Antiviral Agents / pharmacology*
Cell Proliferation / drug effects
Cells, Cultured
Crystallography, X-Ray
Dose-Response Relationship, Drug
Herpesvirus 3, Human / drug effects*
Humans
Microbial Sensitivity Tests
Models, Molecular
Molecular Structure
Pyrimidinones / chemistry
Pyrimidinones / pharmacology*
Structure-Activity Relationship
Triazoles / chemistry
Triazoles / pharmacology*

Substances

Antiviral Agents
Pyrimidinones
Triazoles