Design, synthesis, and evaluation of biological activity of camphor-based oxo-phenylacetamide ester compounds

This study presents the design, synthesis, and biological evaluation of a novel series of amide derivatives based on the fenchol/bornyl scaffold. Systematic screening of biological activity revealed that 3y exhibited significant antifungal activity against both Fusarium oxysporum and Fusarium graminearum , with half-maximal inhibitory concentration (EC 50 ) values of 15.732 mg/L and 19.348 mg/L, respectively. Transcriptomic analysis coupled with molecular docking studies demonstrated that 3y specifically targets ERG13, a key enzyme in ergosterol biosynthesis. This action effectively disrupts fungal cell membrane integrity, induces oxidative stress, and ultimately inhibits hyphal growth and spore germination. Furthermore, density functional theory calculations provided detailed insights into the high-affinity binding mechanism between the compound and its target protein, revealing the molecular basis of its efficacy. This study presents a novel molecular template and design strategy for the development of highly selective, low-risk ergosterol synthesis inhibitors. • Novel camphor-based amide esters were synthesized, with lead compound 3y showing potent antifungal activity (EC 50 = 15.732 and 19.348 mg/L against F. oxysporum and F. graminearum ). • Compound 3y specifically targets ERG13 in ergosterol biosynthesis, as revealed by integrated transcriptomics and molecular docking, disrupting membrane integrity and inducing oxidative stress. • In vivo efficacy and multi-dimensional mechanistic studies confirm 3y as a promising fungicide candidate, providing a solid foundation for developing novel, eco-friendly antifungal agents.