Synthesis and antifungal activity of arecoline derivatives containing amino acid fragments.

Abstract

A series of new arecoline derivatives containing amino acid fragments were synthesized, and their fungicidal activities were investigated. All synthesized compounds were characterized by ¹H NMR, ¹³CNMR, and HRMS. Preliminary bioactivity assays demonstrated that Compounds 3k, 3n, 3p, 3q, 3r, and 3s exhibited significant antifungal activity against Botryosphaeria cactivora, Botryosphaeria dothidea, and Fusarium pseudograminearum at a concentration of 100 μg/mL. Among them, Compound 3s displayed the highest inhibitory activity against Botryosphaeria dothidea (96.63%), surpassing the commercial fungicide chlorothalonil (91.30%). To explore the underlying mechanisms of the compounds, preliminary investigations into the antifungal mechanism involved molecular docking study, scanning electron microscopy and fluorescence microscopy observations, assessments of membrane permeability, and measurements of malondialdehyde content were carried out, respectively. The findings demonstrated that Compound 3s effectively inhibits fungal hyphal growth by compromising the integrity of the hyphal cell membrane. These results indicate that arecoline derivatives containing amino acid benzyl esters have potential as promising fungicides.