2019 Zuccolo SciRep
Dual-active antifungal agents containing strobilurin and SDHI based pharmacophores
Zuccolo M., Kunova A., Musso L., Forlani F., Pinto A., Vistoli G., Gervasoni S., Cortesi P., Dallavalle S.
Control of plant diseases often requires numerous applications of different classes of fungicides to manage the resistance in pathogen populations. A well-establish practice is the use of tank-mixes, which helps to reduce the number of treatments, but can have diverse drawbacks. In this paper we describe the design of bifunctional fungicides, i.e. compounds resulting from conjugation of the toxicophores of fungicides with different mechanisms of action, as a more sustainable alternative for plant pathogen management. The dual fungicides were obtained by merging the toxicophores of two important agricultural fungicides, strobilurins and succinate dehydrogenase inhibitors, into a new chemical entity.
The compounds were tested against important fungal plant pathogens and showed good inhibition of Pyricularia oryzae and Sclerotinia sclerotiorumwith an in vitro mycelium inhibition activity comparable to commercial fungicides. The inhibition of the target enzymes of these fungicides (cytochrome bc1 and the succinate dehydrogenase) confirmed that the new molecules are endowed with a dual mechanism of action. These results were supported by molecular modelling studies, which showed that selected compounds form stable complexes with both cytochrome b subunit and succinate dehydrogenase enzyme. This work can be considered an important first step towards the development of novel dual-action agents with optimized structure and improved interaction with the targets.