Broad-spectrum antifungal activity of spirooxindolo-pyrrolidine tethered indole/imidazole hybrid heterocycles against fungal pathogens

Bioorg Med Chem Lett. 2019 Aug 15;29(16):2059-2063. doi: 10.1016/j.bmcl.2019.07.022. Epub 2019 Jul 13.

Abstract

Invasive fungal infections are one of the leading causes of nosocomial bloodstream infections with a limited treatment option. A series of derivatized spirooxindolo-pyrrolidine tethered indole and imidazole heterocyclic hybrids have been synthesized, and their antifungal activity against fungal strains were determined. Here we characterize the antifungal activity of a specific spirooxindolo-pyrrolidine hybrid, dubbed compound 9c, a spirooxindolo-pyrrolidine tethered imidazole synthesized with a 2-chloro and trifluoromethoxy substituent. The compound 9c exhibited no cytotoxicity against mammalian cell line at concentrations that inhibited fungal strains. Compound 9c also significantly inhibited the fungal hyphae and biofilm formation. Our results indicate that spirooxindolo-pyrrolidine heterocyclic hybrids potentially represent a broad class of chemical agents with promising antifungal potential.

Keywords: 1,3-Dipolar cycloaddition; Antifungal agent; Candida; Cryptococcus; Fungi; Ionic liquids; Minimum inhibitory concentration (MIC); Spirooxindolo-pyrrolidine tethered indole/imidazole; Toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / chemical synthesis
  • Antifungal Agents / pharmacology*
  • Antifungal Agents / toxicity
  • Biofilms / drug effects
  • Candida / drug effects
  • Candida / physiology
  • Cell Line, Tumor
  • Cryptococcus / drug effects
  • Cryptococcus / physiology
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / pharmacology*
  • Imidazoles / toxicity
  • Indoles / chemical synthesis
  • Indoles / pharmacology*
  • Indoles / toxicity
  • Microbial Sensitivity Tests
  • Pyrrolidines / chemical synthesis
  • Pyrrolidines / pharmacology*
  • Pyrrolidines / toxicity
  • Spiro Compounds / chemical synthesis
  • Spiro Compounds / pharmacology*
  • Spiro Compounds / toxicity

Substances

  • Antifungal Agents
  • Imidazoles
  • Indoles
  • Pyrrolidines
  • Spiro Compounds