Abstract
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.
Highlights
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
AF biosynthesis in A. flavus depends on the coordinate expression of a set of genes clustered on chromosome III10, most of them encoding for enzymes directly involved in the multistep biosynthetic pathway, but at least two genes are known to encode for expression regulatory proteins
We recently reported several sets of data concerning the biological activity of molecules, belonging to the class of thiosemicarbazones (TS), that displayed different specificity against one or more developmental regulated process in A. flavus[26,27,28,29,30]: here we compare and investigate how, owing to scaffold modifications, TS derivatives of benzaldehyde and cinnamaldehyde (Fig. 1) change in their antifungal and anti-toxigenic effect, unravelling which structural characteristic is responsible for the observed, specific biological activities
Summary
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. A variety of selective inhibitors of AFs has been found by screening libraries of natural or synthetic m olecules[24,25] This experimental approach allows, beside the discovery of compounds suitable for fighting contamination of agricultural commodities, to acquire new insights into the regulatory mechanisms governing the toxin metabolism. This mostly represents a noteworthy advantage for those strategies that keep an eye on a wider philosophy of environmental intervention, trying to avoid or reduce side-effects on other microbial species that share the same ecological niche with the relevant mycotoxigenic fungi
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