Design and Synthesis of IMR-23, an Oxime Derived from Nitroimidazole as an Immunomodulatory Molecule

Curr Drug Deliv. 2020;17(4):324-332. doi: 10.2174/1567201817666200214110442.

Abstract

Background: Adjuvants have been obtained empirically by trial and error experiments and today, there is a tendency to the rational design of adjuvants candidates, which will increasingly achieve effective and safe products. The aim of this work was to design and evaluate the compound IMR-23 derived from nitroimidazole as an immunomodulatory molecule.

Materials and methods: The IMR-23 molecule was obtained by a condensation reaction, cytotoxicity was tested by the sulforhodamine B assay. Adjuvanticity was evaluated in vivo and in vitro in J774A.1 cells and in the mouse model, respectively.

Results: IMR-23 that did not show cytotoxicity on HeLa, Vero cells and macrophages J774A.1, was able to induce the production of molecules involved in the inflammatory process, such as cytokines and chemokines determined by ELISA, to induce the production of antibodies and to generate antigenspecific cells to ovalbumin and against the antigen GST-L1b.

Conclusion: These results open the possibility of further studies to obtain a proper balance of immunogenicity- toxicity in the use of IMR-23 as an adjuvant molecule.

Keywords: Oxime; adjuvant; antibody; immune response; inflammation; nitroimidazole..

MeSH terms

  • Animals
  • Antibodies / immunology
  • Cell Line
  • Chlorocebus aethiops
  • Cytokines / biosynthesis
  • Dose-Response Relationship, Drug
  • Drug Design*
  • HeLa Cells
  • Humans
  • Immunologic Factors / chemical synthesis
  • Immunologic Factors / chemistry
  • Immunologic Factors / pharmacology*
  • Immunomodulation / drug effects*
  • Mice
  • Molecular Structure
  • Nitroimidazoles / chemistry*
  • Oximes / chemical synthesis
  • Oximes / chemistry
  • Oximes / pharmacology*
  • Structure-Activity Relationship
  • Vero Cells

Substances

  • Antibodies
  • Cytokines
  • Immunologic Factors
  • Nitroimidazoles
  • Oximes