γ‐Lactam‐Based Antifungal Compounds against the Wheat Pathogen Zymoseptoria tritici

Abstract

As new environmentally friendly and effective antifungal agents are deeply needed, efficient ecofriendly strategies were designed to access two series of compounds inspired from natural γ‐lactams. Designed compounds were fully characterized and evaluated as antifungal candidates against Zymoseptoria tritici, the main pathogen on wheat crops. The targeted derivatives were prepared from natural resources using green solvents, simple procedures, and limited purification steps. These bio‐inspired compounds revealed as good candidates for further development of efficient crop protection products. Indeed, the HIT compounds exhibited IC50 around 1 μg/mL and were more active than the references tebuconazole and bixafen towards some multidrug‐resistant strains. Two dozen of derivatives have been obtained for each series and allowed to establish early structure‐activity relationships useful for the development of next generation of γ‐lactam derivatives with improved efficacy.

Antifungal Properties of Hydrazine-Based Compounds against Candida albicans

“…A recent study showed that hydrazine and acyl hydrazone derivatives of 5-pyrrolidine-2-one were effective antifungal agents against a series of 12 fungal strains as well as 3 non-albicans Candida species [ 18 ]. Several hydrazine derivatives have also been found to have good antifungal properties against Zymoseptoria tritici , the main pathogen of wheat plants [ 19 ]. Pyrrolidine-2-one, or γ-lactam 1, is a heterocyclic moiety widespread in many natural compounds.…”

“…Damiens et al demonstrated that the integration of an acylhydrazone link (compound 6 ) resulted in antifungal activity against Z. tritici . However, the same compound did not show any antifungal potential against C. albicans , which implies that C. albicans behaves in a different way from Z. tritici towards this series of compounds, indicating that they have a different biological target [ 19 ].…”