Synthesis, Antifungal Activity, and Molecular Simulation Study of L–Carvone‐Derived 1,3,4‐Oxadiazole‐Thioether Compounds

Abstract

AbstractTo discover potent antifungal molecules with new and distinctive structures, 20 novel L‐carvone‐derived 1,3,4‐oxadiazole‐thioether compounds5 a–5 twere synthesized through multi‐step reaction of L‐carvone, and their structures were confirmed by FT‐IR,1H‐NMR,13C‐NMR, and HR‐MS. The antifungal activities of compounds5 a–5 twere preliminarily tested by in vitro method, and the results indicated that all of the title compounds displayed certain antifungal activities against the eight tested plant fungi, especially forP. piricola. Among them, compound5 i(R=p‐F) with the most significant antifungal activity deserved further study for discovering and developing novel natural product‐based antifungal agents. Moreover, two molecular simulation technologies were employed for the investigation of their structure–activity relationships (SARs). Firstly, a reasonable and effective 3D‐QSAR model was established by the comparative molecular field (CoMFA) method, and the relationship of the substituents linked with the benzene rings and the inhibitory activities of the title compounds againstP. piricolawas elucidated. Then, the binding mode of compound5 i(R=p‐F) and its potential biological target (CYP51) was simulated by molecular docking, and it was found that compound5 icould readily bind with CYP51 in the active site, and the ligand‐receptor interactions involved three hydrogen bonds and several hydrophobic effects.