Synthesis, antifungal activity, and 3d-QSAR study of <i>L-</i> carvone-based pyrazole-oxime ester compounds

Natural products can provide versatile substructures with potential bioactivity and biocompatibility for exploring bioactive compounds. Herein, to explore novel natural product-derived antifungal agents, 21 unreported <i>L</i> -carvone-based pyrazole-oxime ester compounds <b>6a-6u</b> were synthesised using <i>L-</i>carvone as raw material, and structurally characterised by means of FT-IR,¹H NMR,¹³C NMR, and HRMS. The results of the <i>in vitro</i> bioactivity tests showed that the target compounds exhibited certain antifungal activity against the eight tested plant fungi at the concentration of 50 mg/L, especially for <i>Physalospora piricola</i>. The inhibition rates of compounds <b>6e</b> (R = <i>m</i>-Cl) and <b>6c</b> (R = <i>m</i>-F) against <i>P. piricola</i> were 88.3% and 83.9%, respectively, both better than that of the positive control chlorothalonil. Compound <b>6e</b> (R= <i>m</i>-Cl) with the most significant antifungal activity deserves further investigation as the potential leading compound. In addition, the structure-activity relationships (SARs) of the target compounds were investigated by establishing an effective three-dimensional quantitative structure-activity relationship (3D-QSAR) model.