Biological activity study of formononetin‐containing isopropanolamine derivatives: dual effects of membrane penetration and intracellular action

Abstract

BACKGROUNDGlobal crop yields suffer severe losses due to pathogenic infections, and the drug resistance of traditional fungicides has become a prominent issue. Developing new fungicides with high efficiency, environmental friendliness, and low toxicity has become an important task in agricultural plant protection, which also promotes natural product‐derived green pesticides to become a research hotspot.RESULTS30 formononetin derivatives incorporating isopropanolamine moieties were rationally designed and synthesized as potential plant disease control agents. In vitro bioassays against eight phytopathogenic fungi and three bacteria identified several candidates with potent antimicrobial activities. Notably, A28 exhibited the highest efficacy against Phytophthora capsica (Pc) with an EC50 of 4.2 μg/mL, outperforming the commercial fungicide azoxystrobin (Az, 88.2 μg/mL). Meanwhile, A17 demonstrated optimal activity against Xanthomonas oryzae pv. oryzae (Xoo) with an EC50 of 1.8 μg/mL, surpassing thiodiazole‐copper (TC, 87.1 μg/mL). In vivo experiments confirmed their therapeutic potential. At 200 μg/mL, A28 showed a curative activity of 72.3% against eggplant phytophthora rot, superior to Az (63.1%), while A17 exhibited a curative activity of 59.5% against rice bacterial leaf blight, outperforming TC (36.9%). The possible action mechanisms were preliminarily elucidated by experiments including scanning electron microscopy (SEM), fluorescence microscopy (FM), virulence factor assays, and density functional theory (DFT) calculations.CONCLUSIONFormononetin derivatives containing iso‐propanolamine show great potential as novel agents for plant disease control, combining high efficacy and multi‐mechanistic action against both fungal and bacterial pathogens. © 2025 Society of Chemical Industry.