Schiff bases of sulphonamides as a new class of antifungal agent against multidrug-resistant Candida auris

Microbiologyopen. 2021 Aug;10(4):e1218. doi: 10.1002/mbo3.1218.

Abstract

Invasive Candida infections in hospitalized and immunocompromised or critically ill patients have become an important cause of morbidity and mortality. There are increasing reports of multidrug resistance in several Candida species that cause Candidemia, including C. glabrata and C. auris, with limited numbers of antifungal agents available to treat patients with invasive Candida infections. Therefore, there is an urgent need to discover new antifungal agents that work against multidrug-resistant Candida species, particularly C. auris, which has been identified as an emerging global pathogen. In this article, we report a new class of antifungal agents, the Schiff bases of sulphonamides, that show activity against all Candida species tested, with an MIC range of 4-32 µg/ml. Compound 2b showed activity against C. glabrata and a panel of fluconazole-resistant C. auris strains, with MICs of 4-16 µg/ml. The drug-like nature of these Schiff bases offers opportunities to optimize these compounds with medicinal chemistry techniques to obtain more potent analogs that can be progressed toward pre-clinical evaluation.

Keywords: Candida auris; Schiff bases; antifungal resistance; candidemia; sulphonamides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / pharmacology*
  • Candida auris / drug effects*
  • Candida auris / genetics
  • Candidemia / drug therapy*
  • Cell Line
  • Drug Resistance, Multiple, Fungal / genetics
  • Fluconazole / pharmacology
  • Humans
  • Microbial Sensitivity Tests
  • Schiff Bases / chemistry
  • Schiff Bases / pharmacology
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Antifungal Agents
  • Schiff Bases
  • Sulfonamides
  • Fluconazole