Antiaflatoxigenic Thiosemicarbazones as Crop-Protective Agents: A Cytotoxic and Genotoxic Study

Abstract

Aflatoxins are secondary fungal metabolites that can contaminate feed and food. They are a cause of growing concern worldwide, because they are potent carcinogenic agents. Thiosemicarbazones are molecules that possess interesting antiaflatoxigenic properties, but in order to use them as crop-protective agents, their cytotoxic and genotoxic profiles must first be assessed. In this paper, a group of thiosemicarbazones and a copper complex are reported as compounds able to antagonize aflatoxin biosynthesis, fungal growth, and sclerotia biogenesis in Aspergillus flavus. The two most interesting thiosemicarbazones found were noncytotoxic on several cell lines (CRL1790, Hs27, HFL1, and U937), and therefore, they were submitted to additional analysis of mutagenicity and genotoxicity on bacteria, plants, and human cells. No mutagenic activity was observed in bacteria, whereas genotoxic activity was revealed by the Alkaline Comet Assay on U937 cells and by the test of chromosomal aberrations in Allium cepa.

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.…”

“…Condensation with thiosemicarbazide, that easily reacts with the carbonyl group of the natural aldehyde/ketone scaffold and possesses donor atoms suitable to chelate metal ions, was chosen as leading strategy to obtain potentially active compounds. The obtained thiosemicarbazones were then structurally modified to enhance the biological properties (and, in particular, antiaflatoxigenic and antifungal potential) of the parent compounds [ 23 , 27 , 28 , 29 ]. Here we report the comprehensive results of the Aflatox ® Project, and discuss the properties of the best candidate that we have found and that might be proposed as new generation aflatoxin’s containment agent, safe for the human health and the environment.…”

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

“…Aiming in particular at the first two issues, purposive modifications have been applied to benzaldehyde and cinnamaldehyde in order to raise their selectivity and their activity power. The addition of thiosemicarbazide to natural compound derivatives was successfully used to obtain TSs with enhanced antifungal and anti-aflatoxigenic properties 25 , 26 , 28 – 30 . Albeit to a different extent, a significant increase of toxin containment was obtained with the TS derivatives of both aldehydes BeTS, and CiTS (Fig.…”

“…Two wild strains of A. flavus (the aflatoxigenic and sclerotigen strain CR10, and the non-toxigenic strain TOφ) were used to assay the biological activity of TSs, as previously reported 30 , and are available on request from the corresponding author. Strains maintenance and conidia suspensions were obtained in YES-agar [2% (w/v) yeast extract (Difco, Detroit, MI), 5% (w/v) sucrose (Sigma, St Louis, MO), 2% (w/v) agar (Difco, Detroit, MI)], according to Degola et al 33 .…”

“…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 (conidia germination, toxin biosynthesis, sclerotia production) in A. flavus 26 – 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.…”