Sabotage at the Powerhouse? Unraveling the Molecular Target of 2-Isopropylbenzaldehyde Thiosemicarbazone, a Specific Inhibitor of Aflatoxin Biosynthesis and Sclerotia Development in Aspergillus flavus, Using Yeast as a Model System

Molecules. 2019 Aug 16;24(16):2971. doi: 10.3390/molecules24162971.

Abstract

Amongst the various approaches to contain aflatoxin contamination of feed and food commodities, the use of inhibitors of fungal growth and/or toxin biosynthesis is showing great promise for the implementation or the replacement of conventional pesticide-based strategies. Several inhibition mechanisms were found taking place at different levels in the biology of the aflatoxin-producing fungal species such as Aspergillus flavus: compounds that influence aflatoxin production may block the biosynthetic pathway through the direct control of genes belonging to the aflatoxin gene cluster, or interfere with one or more of the several steps involved in the aflatoxin metabolism upstream. Recent findings pointed to mitochondrial functionality as one of the potential targets of some aflatoxin inhibitors. Additionally, we have recently reported that the effect of a compound belonging to the class of thiosemicarbazones might be related to the energy generation/carbon flow and redox homeostasis control by the fungal cell. Here, we report our investigation about a putative molecular target of the 3-isopropylbenzaldehyde thiosemicarbazone (mHtcum), using the yeast Saccharomyces cerevisiae as model system, to demonstrate how the compound can actually interfere with the mitochondrial respiratory chain.

Keywords: aflatoxin inhibitor; mitochondrion; respiratory chain; yeast model system.

MeSH terms

  • Aflatoxins / antagonists & inhibitors*
  • Aflatoxins / biosynthesis
  • Antifungal Agents / chemistry
  • Antifungal Agents / pharmacology*
  • Aspergillus flavus / drug effects
  • Aspergillus flavus / enzymology
  • Aspergillus flavus / genetics
  • Binding Sites
  • Electron Transport / drug effects
  • Electron Transport Complex III / antagonists & inhibitors
  • Electron Transport Complex III / chemistry
  • Electron Transport Complex III / genetics
  • Electron Transport Complex III / metabolism
  • Fungal Proteins / antagonists & inhibitors
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Expression Regulation, Fungal*
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Models, Biological
  • Molecular Docking Simulation
  • Multigene Family
  • Protein Binding
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Thiosemicarbazones / chemistry
  • Thiosemicarbazones / pharmacology*

Substances

  • Aflatoxins
  • Antifungal Agents
  • Fungal Proteins
  • Thiosemicarbazones
  • Electron Transport Complex III