Synthesis, antifungal activity and 3D-QSAR study of novel nopol-based 1,3,4-thiadiazole-thioether compounds

A series of novel nopol derivatives containing 1,3,4-thiadiazole-thioether moiety were synthesized from beta-pinene, which is a natural, abundant and renewable biomass resource. Their structures were characterized by FT-IR, H-1 NMR, C-13 NMR, ESI-MS and elemental analysis. In vitro antifungal activity of the target compounds was preliminarily evaluated against eight tested plant pathogens, including Fusarium oxysporum f. sp. cucumerinum, Cercospora arachidicola, Physalospora piricola, Alternaria solani, Gibberella zeae, Rhizoeotnia solani, Bipolaris maydis and Colleterichum orbicalare. The bioassay results revealed that, at the concentration of 50 mu g/mL, all the target compounds showed certain inhibition activity against the eight tested fungi. Compounds 5f (R = m-OCH3), 5i (R = m-F) and 5r (R = m-I) had excellent inhibition rates of 77.8%, 88.9% and 77.8%, respectively, against P. piricola, showing much better antifungal activity than that of the positive control chlorothalonil. Meanwhile, compound 5 m (R = p-Cl) displayed antifungal activity of 80.7% against R. solani. Furthermore, the analysis of three-dimensional quantitative structure-activity relationship (3D-QSAR) was performed for the relationship between the structures of the target compounds and their antifungal activity against P. piricola by CoMFA method. A reasonable CoMFA model (n = 6; q(2) = 0.597; r(2) = 0.985) was established.