Design, synthesis, and antimicrobial evaluation of novel 1,2,4-trizaole thioether derivatives with a 1,3,4-thiadiazole skeleton

Abstract

The aim of this study was to design and synthesize 17 novel 1,2,4-triazole thioether derivatives containing 1,3,4-thiadiazole thioether. Bioactivity assays indicated that several target compounds exhibited moderate to good antifungal and antibacterial activities. Notably, compound 9d demonstrated significantly stronger antifungal activity against Trichoderma sp. in Morchella esculenta (TSM) and Mucor sp. in Dictyophora rubrovalvata (MSD), with EC₅₀ values of 9.25 and 12.95 μg mL⁻¹, respectively, compared to the commercial fungicide pyrimethanil, which had EC₅₀ values of 35.29 and 15.51 μg mL⁻¹. Furthermore, compound 9d found to have strong antibacterial activity against Pseudomonas syringae pv. actinidiae (PSA) in vitro, with an EC₅₀ of 9.34 μg mL⁻¹, markedly superior to that of thiodiazole copper (81.74 μg mL⁻¹). Additionally, the in vivo anti-PSA assessment revealed therapeutic and protective activities at 200 μg mL⁻¹ of 59.39% and 79.33%, respectively, outperforming thiodiazole copper (38.91% and 67.64%, respectively). According to molecular docking simulations the interaction between compound 9d and FtsZ was mainly due to hydrogen bond formations with GLU-296, ARG-301, LYS-188, ASP-29 and GLY-30. This report suggests that these novel 1,2,4-triazole thioether derivatives featuring a 1,3,4-thiadiazole skeleton may effectively mitigate fungal and bacterial threats to plants.