Sisters in structure but different in character, some benzaldehyde and cinnamaldehyde derivatives differentially tune Aspergillus flavus secondary metabolism

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.

The AFLATOX® Project: Approaching the Development of New Generation, Natural-Based Compounds for the Containment of the Mycotoxigenic Phytopathogen Aspergillus flavus and Aflatoxin Contamination

“…A great variability of efficacy was observed amongst compounds: derivatives from benzaldehyde, benzophenone, cuminaldehyde, cinnamaldehyde, 2-acetylthiophene and cis -jasmone parent compounds proved to be the most active compounds ( Tables S1 and S2 ) [ 23 , 27 , 29 , 32 , 33 , 34 ], while many others did not show any interesting activity.…”

“…Interestingly, amongst all the screened TSs, the highest number of biologically active compounds refers to anti-aflatoxigenic molecules, indicating that probably the majority of molecular/cellular targets belong to secondary metabolism pathways, and thus only in few cases they might severely affect the fungal growth. More remarkably, some molecules were found to show anti-toxigenic potential uncoupled with a significant effect on mycelium development [ 23 , 33 , 34 , 50 ], this is considered particularly interesting in an ecological perspective overall. These selective anti-aflatoxigenic compounds could become considerably interesting for applications aimed at excluding ordinary fungicidal, nonspecific agents.…”

“…Thiosemicarbazones are synthesized following literature methods or as reported in the authors’ previous papers [ 23 , 25 , 27 , 28 , 29 , 32 , 33 , 34 , 35 ]. In general, an equimolar amount of thiosemicarbazide was mixed with the appropriate aldehyde or ketone in absolute ethanol, with a small amount of acetic acid as a catalyst.…”

Double Gamers—Can Modified Natural Regulators of Higher Plants Act as Antagonists against Phytopathogens? The Case of Jasmonic Acid Derivatives

“…Aspergillus flavus strains CR10+ and TOφ strains, previously characterized and described [ 40 , 41 ], belong to the fungal collection of the Laboratory of Mycotoxicology (Dept. of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Italy).…”

A New Photoactivatable Ruthenium(II) Complex with an Asymmetric Bis-Thiocarbohydrazone: Chemical and Biological Investigations

“…Our main interest has been focused on the development of ligands bearing nitrogen and sulfur as donor atoms, and on the synthesis of their metal complexes [ 4 , 5 , 6 , 7 , 8 ]. These compounds, mainly belonging to the class of thiosemicarbazones [ 9 ], are known for their wide range of biological activities and for their ability to chelate metal ions.…”