Discovery of spirooxindole-pyrrolidine heterocyclic hybrids with potent antifungal activity against fungal pathogens

Pathog Dis. 2022 Jun 22;80(1):ftac013. doi: 10.1093/femspd/ftac013.

Abstract

Fungal pathogens mainly Candida and Cryptococcus species causes serious life-threating infections to humans, especially in individuals who are immunocompromised. Increasing frequency of antifungal drug resistance along with paucity of FDA-approved drugs suggest a dire need for new antifungal drugs. Our screening of newly synthesized spirooxindole heterocyclic hybrid compounds revealed that the novel small molecule, DPA-3, has potent antifungal activity without inducing mammalian cell cytotoxicity. Furthermore, DPA-3 significantly reduced hyphal and biofilm formation of Candida albicans ATCC 10231 strain, out-competing two FDA approved antifungal drugs. The results of our study conclude that DPA-3 is a compelling candidate for further development as an antifungal drug.

Keywords: Candida albicans; antifungal activity; biofilm; hyphae.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antifungal Agents* / pharmacology
  • Antifungal Agents* / therapeutic use
  • Biofilms*
  • Candida
  • Candida albicans
  • Humans
  • Mammals
  • Microbial Sensitivity Tests
  • Pyrrolidines / pharmacology

Substances

  • Antifungal Agents
  • Pyrrolidines