Attempts to Access a Series of Pyrazoles Lead to New Hydrazones with Antifungal Potential against Candida species including Azole-Resistant Strains

Molecules. 2021 Sep 27;26(19):5861. doi: 10.3390/molecules26195861.

Abstract

The treatment of benzylidenemalononitriles with phenylhydrazines in refluxing ethanol did not provide pyrazole derivatives, but instead furnished hydrazones. The structure of hydrazones was secured by X-ray analysis. The chemical proof was also obtained by direct reaction of 3,4,5-trimethoxybenzaldehyde with 2,4-dichlorophenylhydrazine. Newly synthesized hydrazones were tested against eight Candida spp. strains in a dose response assay to determine the minimum inhibitory concentration (MIC99). Five compounds were identified as promising antifungal agents against Candida spp. (C. albicans SC5314, C. glabrata, C. tropicalis, C. parapsilosis and C. glabrata (R azoles)), with MIC99 values ranging from 16 to 32 µg/mL and selective antifungal activity over cytotoxicity.

Keywords: Candida albicans; Candida glabrata; Candida species; antifungal agents; hydrazone.

MeSH terms

  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Azoles / pharmacology*
  • Candida / drug effects*
  • Candida / growth & development
  • Drug Resistance, Fungal*
  • Hydrazones / chemistry
  • Hydrazones / pharmacology*
  • Microbial Sensitivity Tests
  • Pyrazoles / chemistry*

Substances

  • Antifungal Agents
  • Azoles
  • Hydrazones
  • Pyrazoles