Design, synthesis and biological activity evaluation of novel imidazo[5,1-b]thiazole derivatives containing a pyrazole ring based on the intermediate derivatization method.

Abstract

Background: A substantial amount of empirical research indicates that the development of novel pesticides through the intermediate derivatization method can significantly enhance the success rate of new pesticide creation while reducing research and development costs. In response to this demand, a series of novel derivatives containing pyrazole imidazo[5,1-b]thiazole were synthesized by the intermediate derivatization method to modify the imine skeleton, which was found to have good antifungal activity in a previous work, and subjecting it to intramolecular nucleophilic substitution reaction.

Results: These compounds showed good performance in antifungal activity tests. Compounds 4f and 18f [median effective concentration (EC₅₀) values 0.98 and 0.95 mg L^-1, respectively] had comparable activity against Sclerotinia sclerotiorum to that of the commercial pesticide boscalid (EC₅₀ = 0.82 mg L^-1). In vivo testing showed that compound 18f had a good protective effect on rape leaves at 40 mg L^-1 concentration. Scanning (SEM) and transmission electron microscopy (TEM) revealed that compound 18f exerted a notable detrimental effect on the integrity of the fungal cell membrane, and thus antifungal activity. Subsequent leakage of cell content, relative conductivity tests, cell membrane permeability assays and reactive oxygen species (ROS) assays showed similar results. Moreover, we evaluated the lower toxicity of compound 18f to aquatic organisms compared to the positive control boscalid through acute toxicity experiments on zebrafish.

Conclusions: In this study, we designed a novel imidazo[5,1-b]thiazole derivative containing a pyrazole ring using the intermediate derivatization method and subsequently evaluated its antifungal activity. The highly efficient and low toxicity compound 18f may become a new candidate antifungal pesticide. This study provides a certain reference value for the development of novel fungicides based on imidazo[5,1-b]thiazole derivatives. © 2025 Society of Chemical Industry.