Design, synthesis and evaluation of hydrazine and acyl hydrazone derivatives of 5-pyrrolidin-2-one as antifungal agents

Bioorg Med Chem Lett. 2020 Jul 1;30(13):127220. doi: 10.1016/j.bmcl.2020.127220. Epub 2020 Apr 28.

Abstract

Twenty-eight 5-pyrrolidine-2-ones decorated by hydrazine or acyl hydrazones groups have been designed, synthesized and evaluated as antifungal agents on a panel of twelve fungal strains and three non albicans candida yeasts species which have demonstrated reduced susceptibility to commonly used antifungal drugs. Half of the target compounds exhibited good to high antifungal activities on at least one strain with MIC50 lower than the control antifungal agent - hymexazol or ketoconazole. 5-Arylhydrazino-pyrrolidin-2-ones were found active and the -NH-NH- linker proved to be essential to maintain the antifungal potential. Compound 2a is a broad-spectrum antifungal, active on 60% of the tested strains. Replacing the hydrazine linker by an acylhydrazone one narrowed the spectrum of activity but pyroglutamylaryl hydrazones, mainly aromatic ones, exhibited good activity, adequate "fungicide-like" properties and were devoted of cytotoxicity.

Keywords: Antifungal agents; Biological screening; Hydrazine; Hydrazone; Pyrrolidin-2-one.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / pharmacology*
  • Drug Design
  • Fungi / drug effects
  • Hydrazones / chemical synthesis
  • Hydrazones / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Pyrrolidinones / chemical synthesis
  • Pyrrolidinones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antifungal Agents
  • Hydrazones
  • Pyrrolidinones