Bisceglie Franco, Degola Francesca, Rogolino Dominga, Giannelli Gianluigi, Orsoni Nicolò, Spadola Giorgio, Pioli Marianna, Restivo Francesco M, Carcelli Mauro, Pelosi Giorgio
Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 11/A, 43124, Parma, Italy.
Sci Rep. 2020 Oct 19;10(1):17686. doi: 10.1038/s41598-020-74574-z.
Great are the expectations for a new generation of antimicrobials, and strenuous are the research efforts towards the exploration of diverse molecular scaffolds-possibly of natural origin - aimed at the synthesis of new compounds against the spread of hazardous fungi. Also high but winding are the paths leading to the definition of biological targets specifically fitting the drug's structural characteristics. The present study is addressed to inspect differential biological behaviours of cinnamaldehyde and benzaldehyde thiosemicarbazone scaffolds, exploiting the secondary metabolism of the mycotoxigenic phytopathogen Aspergillus flavus. Interestingly, owing to modifications on the parent chemical scaffold, some thiosemicarbazones displayed an increased specificity against one or more developmental processes (conidia germination, aflatoxin biosynthesis, sclerotia production) of A. flavus biology. Through the comparative analysis of results, the ligand-based screening strategy here described has allowed us to delineate which modifications are more promising for distinct purposes: from the control of mycotoxins contamination in food and feed commodities, to the environmental management of microbial pathogens, to the investigation of specific structure-activity features for new generation drug discovery.
人们对新一代抗菌药物寄予厚望,为探索各种可能源自天然的分子骨架以合成抗有害真菌传播的新化合物所做的研究努力也十分艰巨。通向明确特别适合药物结构特征的生物学靶点的道路同样漫长且曲折。本研究旨在利用产毒植物病原菌黄曲霉的次级代谢,考察肉桂醛和苯甲醛缩氨基硫脲骨架的不同生物学行为。有趣的是,由于母体化学骨架上的修饰,一些缩氨基硫脲对黄曲霉生物学的一个或多个发育过程(分生孢子萌发、黄曲霉毒素生物合成、菌核产生)表现出更高的特异性。通过对结果的比较分析,本文所述的基于配体的筛选策略使我们能够描绘出哪些修饰对于不同目的更具前景:从控制食品和饲料商品中的霉菌毒素污染,到微生物病原体的环境管理,再到新一代药物发现的特定构效特征研究。