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

• Published in: Journal of agricultural and food chemistry Vol. 71; no. 20; pp. 7631 - 7641
• Main Authors: Hou, Shuaitao, Shi, Huabin, Zhang, Hong, Wu, Zhibing, Hu, Deyu
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 24.05.2023; Amer Chemical Soc
• Subjects: Agricultural and Environmental Chemistry; Agriculture; Agriculture, Multidisciplinary; Antifungal Agents - pharmacology; Chemistry; Chemistry, Applied; Food Science & Technology; Fungi; Life Sciences & Biomedicine; Mandelic Acids; Physical Sciences; Quantitative Structure-Activity Relationship; Science & Technology; Structure-Activity Relationship; 3D-QSAR; mechanism of action; chiral pesticide; 1,3,4-oxadiazole thioether; DL-mandelic acid; fungicidal activity; FUNGICIDAL ACTIVITY; DESIGN; SULFONE DERIVATIVES; ANTIBACTERIAL; TOBACCO; 1; 4-oxadiazole thioether; 3; fungicidalactivity
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.2c09006

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 S-configuration exhibited better in vitro antifungal activity against three plant fungi, such as H3′ (EC50 = 19.3 μg/mL) against Gibberella saubinetii, which was approximately 16 times higher than that of H3 (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 (H3 and H3′) found that the S-configuration compound (H3′) exhibited a stronger ability to destroy the surface structure of G. saubinetii 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.