Synthesis, Antifungal Evaluation, 3D-QSAR, and Preliminarily Mechanism Study of Novel Chiral Mandelic Acid Derivatives

Abstract

To investigate the effect of spatial configuration on the biological activity of the compounds, a series of chiral mandelic acid derivatives with a moiety of 1,3,4-oxadiazole thioether have been designed and synthesized. Bioassay results demonstrated that most title compounds with the <i>S</i>-configuration exhibited better <i>in vitro</i> antifungal activity against three plant fungi, such as <b>H3'</b> (EC₅₀ = 19.3 μg/mL) against <i>Gibberella saubinetii</i>, which was approximately 16 times higher than that of <b>H3</b> (EC₅₀ = 317.0 μg/mL). CoMFA and CoMSIA models were established for 3D-QSAR analysis and provided an important support for further optimization of this series of compounds. Comparing the preliminary mechanism studies between enantiomers (<b>H3</b> and <b>H3'</b>) found that the <i>S</i>-configuration compound (<b>H3'</b>) exhibited a stronger ability to destroy the surface structure of <i>G. saubinetii</i> mycelia, causing the leakage of intracellular substances to accelerate and the growth of the hyphae to be inhibited. The results provided a novel view for the further optimization of this series of active compounds and deep mechanism study of chiral pesticides.