Revolutionizing anti‐fungal strategies: novel Chromone‐based microtubulin target fungicides for Sclerotinia Sclerotiorum of oilseed rape

BACKGROUND Addressing escalating pesticide resistance and food security necessitates sustainable plant pathogen management. This study rationally designed and synthesized novel chromone‐acylhydrazone derivatives engineered to target fungal tubulin, aiming to provide new avenues for disease control. RESULTS We successfully designed and synthesized a series of novel chromone‐acylhydrazone derivatives. Compound H9 emerged as a highly potent lead, exhibiting remarkable inhibitory activity against Sclerotinia sclerotiorum with an EC 50 of 0.23 μg mL −1 . Mechanistic studies revealed that H9's 3‐fluorobenzoylhydrazide moiety disrupts microtubule polymerization via critical hydrogen bonding, while the chromone core facilitates favorable π‐alkyl interactions. H9 demonstrated promising pharmacokinetic profiles and negligible mammalian toxicity. Further, encapsulation within polyurethane microcapsules (H9‐Loaded PU MCs) yielded an efficient (89.12% encapsulation efficiency) sustained‐release system, significantly improving foliar adhesion and fungicidal efficacy. CONCLUSIONS This work highlights H9 as a groundbreaking, safe fungicide, whose exceptional bioactivity, favorable safety profile, and advanced sustained‐release formulation technology offer a powerful solution for next‐generation sustainable pest management. This underscores the significant potential of rational molecular design coupled with advanced formulation technology in advancing pesticide candidates with green potential.