A new small-molecule KRE2 inhibitor against invasive Candida parapsilosis infection

Future Microbiol. 2017 Nov:12:1283-1295. doi: 10.2217/fmb-2017-0065. Epub 2017 Oct 4.

Abstract

Aim: To investigate the antifungal activity of MOL3, a small molecule that was selected by virtual screening, against Candida spp.

Materials & methods: The antifungal activity of MOL3 was evaluated using standard strains and clinical isolates. Activity was evaluated in both in vitro tests and animal models.

Results: The minimum fungicidal concentration of MOL3 against Candida spp. ranged from 16 to 128 mg/l. MOL3 at the sub-minimum fungicidal concentration inhibited hyphal elongation. The remaining yeast cells presented morphological changes and were metabolically inactive. MOL3 was toxicologically inert both in vitro and in the animal model. MOL3 also reduced experimental systemic infection by C. parapsilosis in mice.

Conclusion: The selection of MOL3 by virtual screening was successful, revealing a promising antifungal candidate.

Keywords: KRE2 protein; invasive candidiasis; virtual screening.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Antifungal Agents / pharmacology*
  • Antifungal Agents / therapeutic use
  • Candida parapsilosis / drug effects*
  • Candidiasis, Invasive / drug therapy*
  • Computer Simulation
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Fungal Proteins / antagonists & inhibitors*
  • Male
  • Mannosyltransferases / antagonists & inhibitors*
  • Mice
  • Mice, Inbred BALB C

Substances

  • Antifungal Agents
  • Enzyme Inhibitors
  • Fungal Proteins
  • Mannosyltransferases