Strategies to overcome resistance in phytopathogenic fungi using multitarget natural and nature-inspired stilbenoids

Introduction: Phytopathogenic fungi heavily affect crop production worldwide, thus representing a serious threat for food security and availability (1). Moreover, intensive monoculture cropping and treatment by fungicides with a single-site mechanism of action contribute to the emergence of resistant strains (2). For their high diversity and versatility, natural products are considered the first step towards the developement of new biofungicides. Among them, stilbenoids, as phytoalexins overexpressed from plants in response to stress conditions (3), represent suitable substrates for the obtainment of multitarget agrochemicals, potentially able to limit the onset and spread of fungicide resistance. Material & Methods: The reported stilbenoids were synthesized, purified and chemically characterized. The fungicide activity was evaluated as micelyum growth inhibition on P. oryzae (wild-type and resistant strains). Results: Resveratrol, its methylated derivatives, and the corresponding dimers were prepared by chemical or chemoezymatic protocols, resulting in a small collection of multitarget compounds, based on the stilbenoid core. Natural deoxyrhapontigenin resulted as the best potential antifungal agent, inhibiting the mycelium growth by 60-80%, both on wild-type and resistant strains. Conclusion: A collection of stilbenoid-derivatives was prepared and tested as multitarget antifungal agents. Further efforts are needed to improve the activity profile of the most promising compounds, especially against resistant strains.