Study on synthesis and antifungal activity of 2-(2-benzylaminophenyl)-thiazole-4-carboxylic acid derivatives

Structural optimization using natural products as leads is an effective strategy for the discovery of novel agrochemicals. To discover benzylamine-containing agricultural fungicides, a series of 2-(2-benzylaminophenyl)-thiazole-4-carboxylic acid derivatives (Z1-Z18) were designed and synthesized using the natural product Thiasporine A as the lead compound via active substructure splicing. The fungicidal activities of the target compounds were subsequently evaluated. The results of the antifungal assay demonstrated that all tested compounds exerted inhibitory effects against the four selected phytopathogens at 50 μg/mL, with the most pronounced activity against Sclerotinia sclerotiorum. Compound Z1 showed significant efficacy against S. sclerotiorum, with an EC₅₀ value of 0.35 μg/mL, which was comparable to that of carbendazim (0.36 μg/mL) but markedly superior to that of the lead compound Thiasporine A (78.77 μg/mL). Meanwhile, compound Z10 exhibited enhanced antifungal activity against Rhizoctonia solani with an EC₅₀ of 2.28 μg/mL, outperforming ferimzone (10.50 μg/mL). The results demonstrated that compound Z1 provided better inhibitory efficacy against sclerotia formation than carbendazim at 1.25 μg/mL. The inhibition rate of compound Z1 on sclerotia formation of S. sclerotiorum was 33.1%, which was superior to that of carbendazim (23.5%). The results of the in vitro leaf-disc assay showed that compound Z1 exhibited certain antifungal activity in both protective activity and curative activity. At a concentration of 200 μg/mL, the protective and curative effects were 34.0% and 36.6%, respectively. This research lays a foundation for the development of novel benzylamino-phenylthiazole-based fungicides.