1,2,4-Oxadiazole-Based Bio-Isosteres of Benzamides: Synthesis, Biological Activity and Toxicity to Zebrafish Embryo

Int J Mol Sci. 2021 Feb 27;22(5):2367. doi: 10.3390/ijms22052367.

Abstract

To discover new compounds with broad spectrum and high activity, we designed a series of novel benzamides containing 1,2,4-oxadiazole moiety by bioisosterism, and 28 benzamides derivatives with antifungal activity were synthesized. These compounds were evaluated against four fungi: Botrytis cinereal, FusaHum graminearum, Marssonina mali, and Thanatephorus cucumeris. The results indicated that most of the compounds displayed good fungicidal activities, especially against Botrytis cinereal. For example, 10a (84.4%), 10d (83.6%), 10e (83.3%), 10f (83.1%), 10i (83.3%), and 10l (83.6%) were better than pyraclostrobin (81.4%) at 100 mg/L. In addition, the acute toxicity of 10f to zebrafish embryo was 20.58 mg/L, which was classified as a low-toxicity compound.

Keywords: 1,2,4-oxadiazole; benzamides; biological activity; synthesis; toxicity.

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology*
  • Ascomycota / drug effects
  • Basidiomycota / drug effects
  • Benzamides / chemical synthesis
  • Benzamides / chemistry
  • Benzamides / pharmacology*
  • Benzamides / toxicity
  • Botrytis / drug effects
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / microbiology
  • Fusarium / drug effects
  • Microbial Sensitivity Tests
  • Oxadiazoles / chemical synthesis
  • Oxadiazoles / chemistry
  • Oxadiazoles / pharmacology*
  • Oxadiazoles / toxicity
  • Zebrafish / embryology
  • Zebrafish / microbiology*

Substances

  • Antifungal Agents
  • Benzamides
  • Oxadiazoles

Supplementary concepts

  • Botrytis cinerea
  • Fusarium graminearum
  • Marssonina mali
  • Thanatephorus cucumeris