Department of Chemistry, Life Sciences and Environmental Sustainability and CIRCMSB (Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici), Università di Parma, Parco Area delle Scienze, 43124, Parma, Italy.
Department of Medical and Surgical Specialities, Radiological Sciences and Public Health, University of Brescia, Viale Europa 11, 25123, Brescia, Italy.
Sci Rep. 2017 Sep 11;7(1):11214. doi: 10.1038/s41598-017-11716-w.
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.
黄曲霉毒素对食物的污染问题目前构成了一种社会紧急情况，因为它们对人类和动物的健康构成了严重威胁。另一方面，必须控制农药的使用，因为这会在食物和环境中产生长期残留。在这里，我们展示了一系列基于硫代缩氨基脲支架的螯合配体的合成，这些配体将被评估其抗真菌和抗黄曲霉毒素的效果。从具有已知抗真菌特性的天然来源的分子开始，我们引入了硫代基团，然后合成了相应的铜配合物。一些分子在 100μM 时对黄曲霉毒素的抑制率达到 67-92%。最有效的化合物被评估其对人细胞的细胞毒性作用。虽然所有的铜配合物在微摩尔范围内都表现出很高的细胞毒性，但其中一种配体对细胞增殖没有影响。这个命中物被选择用于进一步分析其在细菌、植物和人类细胞中的致突变性和遗传毒性。数据分析强调了对作为作物保护剂开发的命中化合物进行安全性评估的重要性，同时表明硫代缩氨基脲支架是开发黄曲霉毒素抑制剂的良好起点。
