Synthesis, antifungal activity and 3D-QSAR study of novel acyl thiourea compounds containing gem-dimethylcyclopropane ring

A series of novel acyl thiourea compounds containing gem-dimethylcyclopropane ring were designed and synthesized by multi-step reactions in search of novel antifungal molecules. Structures of all the target compounds were characterized by spectral techniques of UV–vis, FT-IR, 1H-NMR, 13C-NMR, and ESI–MS. The antifungal activity of the target compounds was preliminarily evaluated by agar dilution method. The antifungal bioassay revealed that, at 50 μg/mL, compounds 5h (R = o-F), 5m (R = p-Br), and 5n (R = o-NO2) showed the same antifungal activity of 73.6% against Physalospora piricola, which was comparable than that of the positive control. Furthermore, against Gibberella zeae, compounds 5k (R = m-Cl), 5l (R = m-Br), 5m (R = p-Br), and 5n (R = o-NO2) displayed the same antifungal activity of 75.6%, and compound 5o (R = p-NO2) displayed antifungal activity of 78.8%, which were all better than that of the positive control. The preliminary analysis of 3D-QSAR model was performed to study the effect of molecular structure on biological activity using the comparative molecular field analysis (CoMFA) method. The results showed 3D-QSAR model (r2 = 0.995, q2 = 0.503) was reasonable and effective.