Thiosemicarbazone scaffold for the design of antifungal and antiaflatoxigenic agents: evaluation of ligands and related copper complexes.

The issue of food contamination by aflatoxins presently constitutes a social emergency, since they
represent a severe risk for human and animal health. On the other hand, the use of pesticides has to
be contained, since this generates long term residues in food and in the environment. Here we present
the synthesis of a series of chelating ligands based on the thiosemicarbazone scaffold, to be evaluated
for their antifungal and antiaflatoxigenic effects. Starting from molecules of natural origin of known
antifungal properties, we introduced the thio- group and then the corresponding copper complexes
were synthesised. Some molecules highlighted aflatoxin inhibition in the range 67–92% at 100 μM.
The most active compounds were evaluated for their cytotoxic effects on human cells. While all the
copper complexes showed high cytotoxicity in the micromolar range, one of the ligand has no effect
on cell proliferation. This hit was chosen for further analysis of mutagenicity and genotoxicity on
bacteria, plants and human cells. Analysis of the data underlined the importance of the safety profile
evaluation for hit compounds to be developed as crop-protective agents and at the same time that
the thiosemicarbazone scaffold represents a good starting point for the development of aflatoxigenic
inhibitors.