Structural Investigation and Molecular Modeling Studies of Strobilurin-Based Fungicides Active against the Rice Blast Pathogen Pyricularia oryzae |
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| Authors: | Andrea Kunova Luca Palazzolo Fabio Forlani Giorgia Catinella Loana Musso Paolo Cortesi Ivano Eberini Andrea Pinto Sabrina Dallavalle |
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| Affiliation: | 1.Department of Food, Environmental and Nutritional Science (DeFENS), University of Milan, 20133 Milan, Italy; (A.K.); (F.F.); (G.C.); (L.M.); (P.C.); (S.D.);2.Department of Pharmacological and Biomolecular Sciences (DiSFeB), University of Milan, 20133 Milan, Italy;3.Data Science Research Center (DSRC), University of Milan, 20133 Milan, Italy |
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| Abstract: | The increasing emergence of fungicide-resistant pathogens requires urgent solutions for crop disease management. Here, we describe a structural investigation of new fungicides obtained by combining strobilurin and succinate dehydrogenase inhibitor pharmacophores. We identified compounds endowed with very good activity against wild-type Pyricularia oryzae, combined in some cases with promising activity against strobilurin-resistant strains. The first three-dimensional model of P. oryzae cytochrome bc1 complex containing azoxystrobin as a ligand was developed. The model was validated with a set of commercially available strobilurins, and it well explains both the resistance mechanism to strobilurins mediated by the mutation G143A and the activity of metyltetraprole against strobilurin-resistant strains. The obtained results shed light on the key recognition determinants of strobilurin-like derivatives in the cytochrome bc1 active site and will guide the further rational design of new fungicides able to overcome resistance caused by G143A mutation in the rice blast pathogen. |
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| Keywords: | rice blast crop protection cytochrome bc1 complex antifungal compounds homology modeling molecular docking |
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