Design, Synthesis, Antifungal Evaluation, and Quantitative Structure-Activity Relationship of Novel Indole Derivatives Containing the Imidazo[2,1-b]thiazole Moiety against Phytopathogenic Fungi

Fungal pathogens severely impair the essential physiological and biochemical processes of plants, triggering infections, undermining plant vitality, and ultimately leading to diminished agricultural productivity. To explore new and efficient antifungal agents to deal with the serious destruction of important silvicultural species, a series of new indole derivatives containing the imidazo[2,1-b]heterocycle were designed and synthesized, and their antifungal activities against several fungal species, such as Cytospora chrysosperma (C. c), Sphaeropsis sapinea(S. s), Alternaria. alternata (A. a), Rhizoctonia solani (R. s), Magnaporthe oryzae (M. o), Botrytis cinerea (B. c), and Fusarium oxysporum (F. o), were evaluated by the mycelial growth rate method. The results showed that the EC₅₀ of DL-21 reached 4.13 μg/mL against C. c. Most of the compounds showed more than 60% inhibition against S. s, and among them, the EC₅₀ of DL-27 reached 11.73 μg/mL, which is of great significance for the protection of tree species. The results of SEM and related experiments on the effects on cell membranes demonstrated that the compounds caused damage to the integrity of the mycelium and cell membranes, thereby inhibiting mycelial growth and disrupting the permeability of the cell membranes. The results of the reactive oxygen species assay showed that mycelium treated with the compounds altered the production of endogenous reactive oxygen species. The QSAR model demonstrated that structural factors (positively correlated with biological activity) and molecular polarizability descriptors (negatively correlated with biological activity) may control the activity of these compounds. In vivo tests demonstrated that at identical concentrations, DL-27 exhibited superior control efficacy against poplar leaf infections compared with the commercially available fungicide carbendazim. Research demonstrates that indole derivatives incorporating imidazo[2,1-b]heterocycle structures exhibit marked antifungal efficacy against phytopathogenic fungi, positioning them as promising candidates for novel fungicide development.