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Binding mode of dihydroquinazolinones with lysozyme and its antifungal activity against Aspergillus species

J Photochem Photobiol B. 2016 Aug:161:71-9. doi: 10.1016/j.jphotobiol.2016.05.005. Epub 2016 May 7.

Abstract

Aspergillosis is one of the infectious fungal diseases affecting mainly the immunocompromised patients. The scarcity of the antifungal targets has identified the importance of N-myristoyl transferase (NMT) in the regulation of fungal pathway. The dihydroquinazolinone molecules were designed on the basis of fragments responsible for binding with the target enzyme. The aryl halide, 1(a-g), aryl boronic acid and potassium carbonate were heated together in water and dioxane mixture to yield new CC bond formation in dihydroquinazolinone. The bis(triphenylphosphine)palladium(II) dichloride was used as catalyst for the CC bond formation. The synthesized series were screened for their in vitro antifungal activity against Aspergillus niger and Aspergillus fumigatus. The binding interactions of the active compound with lysozyme were explored using multiple spectroscopic studies. Molecular docking study of dihydroquinazolinones with the enzyme revealed the information regarding various binding forces involved in the interaction.

Keywords: Antifungal activity; Aspergillosis; Dihydroquinazolinones; Lysozyme; N-myristoyl transferase; Spectroscopy.

MeSH terms

  • Antifungal Agents / chemistry
  • Antifungal Agents / metabolism*
  • Antifungal Agents / pharmacology
  • Aspergillus fumigatus / drug effects
  • Aspergillus niger / drug effects
  • Binding Sites
  • Catalysis
  • Circular Dichroism
  • Microbial Sensitivity Tests
  • Molecular Docking Simulation
  • Muramidase / chemistry
  • Muramidase / metabolism*
  • Palladium / chemistry
  • Protein Binding
  • Protein Structure, Tertiary
  • Quinazolinones / chemistry
  • Quinazolinones / metabolism*
  • Quinazolinones / pharmacology
  • Spectrometry, Fluorescence
  • Spectrophotometry, Ultraviolet

Substances

  • Antifungal Agents
  • Quinazolinones
  • Palladium
  • Muramidase
  • palladium chloride