Abstract
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.
Highlights
The direct control of mycotoxin-producing fungi by using synthetic fungicides is still the most effective way to intervene, but it is well known that the extensive use of fungicides generates long term residues in food and in the environment[5]
Some studies suggested that metal ions can influence the growth and the mycotoxin production of the toxigenic fungi A. flavus and F. graminearum and that this effect can be related to the ability of metal ions to intervene on the pattern of gene expressions of A. flavus[9, 11]
Starting from molecules of natural origin, like vanillin and its derivatives, we introduced the thio- group in the perspective to obtain more potent compounds; copper complexes were synthesised, with the aim to synergistically improve the capability of the free ligands to inhibit toxin production
Summary
The direct control of mycotoxin-producing fungi by using synthetic fungicides is still the most effective way to intervene, but it is well known that the extensive use of fungicides generates long term residues in food and in the environment[5]. Concerns on food safety and environmental health, combined with the global issue of emerging resistant pest strains, make urgent to develop novel crop-protective agents[6] In this scenario, the exploitation of bioactive natural sources to obtain new agents with novel modes of actions may represent an innovative, successful strategy to minimize at the same time mycotoxin production and the use of harmful pesticides. Thiosemicarbazones represent a very attractive class of metal-chelating ligands for their coordinating versatility and the possibility to modify the molecular backbone and tuning their physical and chemical properties They have a great variety of biological properties both as free ligands and as metal complexes[12]. Best hits were evaluated for their toxic and genotoxic activities on bacteria and plants cells
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