Synthesis and Biological Activity of New Hydrazones Based on N-Aminomorpholine

Molecules. 2024 Jul 30;29(15):3606. doi: 10.3390/molecules29153606.

Abstract

The data on the synthesis of N-aminomorpholine hydrazones are presented. It is shown that the interaction of N-aminomorpholine with functionally substituted benzaldehydes and 4-pyridinaldehyde in isopropyl alcohol leads to the formation of corresponding hydrazones. The structure of the synthesized compounds was studied by 1H and 13C NMR spectroscopy methods, including the COSY (1H-1H), HMQC (1H-13C) and HMBC (1H-13C) methodologies. The values of chemical shifts, multiplicity, and integral intensity of 1H and 13C signals in one-dimensional NMR spectra were determined. The COSY (1H-1H), HMQC (1H-13C), and HMBC (1H-13C) results revealed homo- and heteronuclear interactions, confirming the structure of the studied compounds. The antiviral, cytotoxic, and antimicrobial activity of some synthesized hydrazones were investigated. It is shown that 2-((morpholinoimino)methyl)benzoic acid has a pronounced viral inhibitory property, comparable in its activity to commercial drugs Tamiflu and Remantadine. A docking study was performed using the influenza virus protein models (1930 Swine H1 Hemagglutinin and Neuraminidase of 1918 H1N1 strain). The potential binding sites that are complementary with 2-((morpholinoimino)methyl)benzoic acid were found.

Keywords: 3-acetoxy-isoindolin-1-ones; N-aminomorpholine; NMR spectroscopy; antiviral activity; functionally substituted benzaldehydes; hydrazones; molecular modeling; o-formyl benzoic acid.

MeSH terms

  • Animals
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Humans
  • Hydrazones* / chemical synthesis
  • Hydrazones* / chemistry
  • Hydrazones* / pharmacology
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation*
  • Molecular Structure
  • Morpholines* / chemical synthesis
  • Morpholines* / chemistry
  • Morpholines* / pharmacology
  • Structure-Activity Relationship

Substances

  • Hydrazones
  • Morpholines
  • Antiviral Agents

Grants and funding

Research work was carried out within the framework of the State Fund AP14869941 of the Science Committee of the Ministry of Science and Higher Education of the Republic of Kazakhstan.