Lihui Shao, Yinyin Wu, Xianqun Hu, Bo Zhang, Xiang Zhou, Song Yang
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: . 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. © 2026 Society of Chemical Industry.