Design, synthesis, and biological evaluation of novel luteoride A derivatives against phytopathogenic fungi and bacteria

Abstract

BACKGROUNDPlant diseases caused by phytopathogenic fungi and bacteria represent a critical barrier to sustainable agriculture, significantly compromising crop yield and quality. Natural products have been a significant source of effective and low‐risk pesticides. In this study, a series of novel indole derivatives, 4a–4o and 5a–5o, were synthesized based on the structure of luteoride A and evaluated for their antimicrobial properties.RESULTSCompound 4c showed excellent in vitro activity against Valsa mali with a median effective concentration (EC50) value of 2.05 mg/L, outperforming luteoride A (EC50 = 12.8 mg/L) and approaching the commercial fungicide trifloxystrobin (EC50 = 1.44 mg/L). In vivo experiments further confirmed the promising protective effects of compound 4c against V. mali on isolated apples and detached branches. Mechanistic investigations suggested that compound 4c potentially inhibits V. mali by binding to complex III of the mitochondrial respiratory chain. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions indicate that compound 4c may possess good aqueous solubility and low toxicity. Moreover, compound 5i exhibited significant antibacterial activity, particularly against Ralstonia solanacearum, with an EC50 value of 7.18 mg/L, surpassing luteoride A (EC50 > 100 mg/L) and the positive control bismerthiazol (EC50 = 76.7 mg/L).CONCLUSIONThis study provides fundamental support for the development of luteoride A derivatives as emerging antimicrobial agents for crop protection. © 2025 Society of Chemical Industry.