Discovery of Isopropanolamine Derivatives as Potential Antifungal Agrochemicals

Given the substantial losses in crop yields resulting from fungal diseases, it is imperative to develop highly efficient antifungal agents with novel chemical skeletons and mechanisms of action to overcome resistance to traditional fungicides. Isopropanolamine, as a versatile chemical fragment, has garnered significant interest due to its diverse biological activities in pharmaceutical research. Our previous research verified its inhibitory effect on fungal phosphatidic acid phosphatase. To elucidate the structure–activity relationship of isopropanolamine derivatives, we designed a series of novel compounds using protein modeling and reverse batch docking, which exhibited potent antifungal properties. Notably, (R)-B17 demonstrated a 41-fold greater potency against Fusarium graminearum than the commercial fungicide boscalid (EC₅₀= 7.14 μM vs. 294 μM). Similarly, (R)-C22 showed a 34-fold enhanced inhibition of Monilinia fructicola compared to azoxystrobin (EC₅₀= 1.82 vs. 62.6 μM). Computational approaches─including molecular docking, molecular dynamics simulations, and quantum chemical calculations─elucidated binding affinities for target proteins. These findings further indicate that stereochemical configurations critically influence simulation outcomes, thereby explaining the differential biological activities of these chiral molecules.