Design and synthesis of novel imidazo[1,2-b]pyridazine derivatives bearing arylhydrazine and dithioacetal groups as potential antifungal agents.

Abstract

BACKGROUND Given the issues of high toxicity and escalating fungicide resistance associated with the prolonged use of existing agricultural fungicide agents, the exploration and development of new, efficient, and low-toxicity small-molecule fungicides is of significant importance. RESULTS In this study, several series of imidazo[1,2-b]pyridazine derivatives incorporating acylhydrazine, sulfonylhydrazine, amide, and dithioacetal pharmacophores were designed and synthesized. Preliminary antifungal activity assays revealed that compounds 5c, 5d, 5n, 7b, and 7c exhibited broad-spectrum and potent inhibitory activities against various plant pathogenic fungi. Notably, compound 5d demonstrated superior protective and curative effects compared with chlorothalonil against apple branches and potatoes infected by Valsa mali and Fusarium solani, respectively. In addition, 5d exhibited more promising protective and curative effects than boscalid against Chinese cabbages and tobacco infected by Alternaria brassicae and Alternaria alternata, respectively. Furthermore, preliminary mechanistic studies indicated that compound 5d exerts its antifungal effects by inhibiting spore germination and germ tube growth, as well as disrupting the integrity and permeability of the mycelial cell wall. Concurrently, the highly active compounds exhibited favorable safety profiles at the cellular level. CONCLUSION This study lays the foundation for the potential application of imidazo[1,2-b]pyridazine-based derivatives as novel fungicide candidates. © 2025 Society of Chemical Industry.