Synthesis, Antifungal Activity, and Molecular Docking Study of Novel 3‐Carene‐Derived 4‐Substituted Phenyl‐1,2,4‐Triazolinthiones Bearing gem‐Dimethylcyclopropane Moiety

For exploring new natural product-based leading compounds with antifungal activity, 15 novel 3-carene-derived 4-substituted phenyl-1,2,4-triazolinthiones 7a ~ 7o bearing gem-dimethylcyclopropane moiety were synthesized and structurally characterized by UV-Vis, FT-IR, 1H NMR, 13C NMR, ESI-MS and elemental analysis. The preliminary bioassay at 50 μg/mL showed that all of the target compounds exhibited certain in vitro inhibitory activities against the eight tested fungi, in which compound 7g (R = m, p-Cl) displayed better inhibition activity (85.0%) against P. piricola than that of the positive control Chlorothalonil. Furthermore, a reasonable and effective 3D structure of phytofungal CYP51 was constructed by homology modeling. Molecular docking study revealed that the total scores of all the target compounds were higher than that of Prothioconazole. In addition, it was found that compound 7g could readily embed into the binding site, and therein shared similar interactions with the case of Prothioconazole. Thus, compound 7g deserved further study as an antifungal leading compound.